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1、ISSUE 14,OCTOBER 20232023HIV MARKET REPORTThe state of HIV treatment,testing,and prevention in low-and middle-income countriesCLINTON HEALTH ACCESS INITIATIVE2 Clinton Health Access Initiative,Inc.(CHAI)2023DISCLAIMERThe data sources primarily used for analysis in the report include CHAI country tea

2、ms,ministry of health counterparts,stakeholder resources and conversations(e.g.Global Fund,PEPFAR,UNAIDS,Unitaid,WHO,and civil society partners),and published research.CHAI has taken precautions to verify the information shared in the report.However,the analysis in the report is not exhaustive,and t

3、he responsibility for the interpretation and use of the material lies with the reader.The mention of specific companies or products does not imply CHAIs endorsement or recommendation.ACKNOWLEDGEMENTThis report was made possible through the generous support of Unitaid,with complementary support from

4、the UK Foreign,Commonwealth&Development Office and the Bill&Melinda Gates Foundation.Front Cover:A health worker performs a heel prick on an infant in Cambodia.Blood is then added to a dried blood spot specimen card,which will be used to perform a test for early infant diagnosis of HIV.Back Cover:A

5、pharmacist in Zimbabwe dispenses pediatric dolutegravir to caregivers.TABLE OF CONTENTSACRONYMS 4AT-A-GLANCE 5GENERAL TRENDS 6PREVENTION 11TESTING 18ADVANCED HIV DISEASE 21ADULT TREATMENT 25PEDIATRIC TREATMENT 30TREATMENT MONITORING 35APPENDIX A:FORECASTED API DEMAND IN GA LMICs 38APPENDIX B:CHAI AR

6、V BENCHMARK PRICE COMPARISON LIST 39APPENDIX C:NOTES ON METHODOLOGY 40APPENDIX D:REFERENCES 412023 HIV MARKET REPORT3CLINTON HEALTH ACCESS INITIATIVE4ACRONYMSARVAntiretroviralARTAntiretroviral therapyAMPAntibody mediated preventionAIDSAcquired immunodeficiency syndromeAHDAdvanced HIV diseaseAGYWAdol

7、escent girls and young womenABCAbacavir5FCFlucytosine3TCLamivudineBICBictegravir3HPThree months of weekly RPT+INH for TPT1LFirst-line2LSecond-lineATV/rAtazanavir/ritonavirAZTZidovudineCMCryptococcal meningitisCLHIVChildren living with HIVCHAIClinton Health Access InitiativeCABCabotegravirCrAgCryptoc

8、occal antigenDVRDapivirine vaginal ringDTGDolutegravirDPPDual prevention pillDRV/rDarunavir/ritonavirEXWEx-worksEFVEfavirenzEIDEarly infant diagnosisFDCFixed-dose combinationHIVHuman immunodeficiency virusGAGeneric-accessibleFTCEmtricitabineHIVSTHIV self-testNRTINucleoside reverse transcriptase inhi

9、bitorMPTMultipurpose prevention technologyLPV/rLopinavir/ritonavirLMICLow-and middle-income countryLENLenacapavirL-AmBLiposomal amphotericin BKPsKey populationsISLIslatravirINHIsoniazidINSTIIntegrase strand transfer inhibitorNNRTINon-nucleoside reverse transcriptase inhibitorpDTGPediatric DTG(10 mg)

10、scored,dispersiblePADOPediatric ARV Drug OptimizationOIOpportunistic infectionNVPNevirapineOBROptimized background regimenPEPFARPresidents Emergency Plan for AIDS ReliefPIProtease inhibitorRPTRifapentine POCPoint-of-carePLHIVPeople living with HIVTBTuberculosisTAFTenofovir alafenamide fumarateDORDor

11、avirinePrEPPre-exposure prophylaxisRPVRilpivirineTDFTenofovir disoproxil fumarateUS FDAUnited States Food and Drug AdministrationTPTTB preventive therapyTLDTDF+3TC+DTGUNAIDSJoint United Nations Program on HIV/AIDSWHOWorld Health OrganizationVMMCVoluntary medical male circumcisionVLViral loadDBSDried

12、 blood spotpALDPediatric ABC+3TC+DTGCAB-LALong-acting cabotegravirANCAntenatal careAPWGARV Procurement Working GroupMPPMedicines Patent PoolSRHSexual and reproductive healthSSASub-Saharan AfricaMOHMinistry of healthDRTDrug resistance testingRIFRifampicinbNABsBroadly neutralizing antibodiesXTCEmtrici

13、tabine or lamivudineMAPMicroarray patchYOYYear-over-yearU=UUndetectable equals untransmittableTLETDF+3TC+EFVSCSubcutaneousDSDDifferentiated service deliveryGAP-fGlobal Accelerator for Pediatric FormulationsHBVHepatitis B virusHBCHepatitis C virusIMIntramuscularLEVILong-acting early viral inhibitionL

14、FALaterial flow assayLGBTQLesbian,gay,bisexual,transgender,queer or questioningMDRMulti-drug resistantNCDNon-communicable diseasesPPPYPer person per yearPQPrequalificationpDRV/rPediatric darunavir/ritonavirpTAFPediatric tenofovir alafenamide fumarateAT-A-GLANCEHIV Overview,2022HIV PreventionAdvanced

15、 HIV DiseaseHIV TestingAdult HIV TreatmentPediatric HIV TreatmentHIV Treatment Monitoring39M37.5M Adults1.5M ChildrenPEOPLE LIVING WITH HIV(PLHIV)28.9M8.6M880K620K77%ADULT(15+)TREATMENT COVERAGE57%PEDIATRIC(0-14)TREATMENT COVERAGEOn Treatment Not on TreatmentOn Treatment Not on Treatment86%89%GLOBAL

16、 PROGRESS TOWARD UNAIDS 2025 GOALSof PLHIV know their statuswho know their status on ARTon ART have suppressed viral loadsGap to 95-95-95 targets as of Dec 2022NEW HIV INFECTIONSAIDS-RELATED DEATHS1.3M130K Children(0-14)1.2M Adults(15+)84K Children(0-14)540K Adults(15+)630K4 Doses/weekof oral TDF/FT

17、C found to be associated with high PrEP effectiveness in cisgender women,demonstrating a comparableadherence-efficacy relationship to cisgender men who have sex with men 1.9M Peoplein LMICs received oralPrEP at least once in 2022No Risk of Sexual Transmissionwhen PLHIV have an undetectable viral loa

18、d(VL)and negligible risk when VL is suppressed but detectable(under 1,000 copies/mL),according to a new WHO brief160K Childrenon pDTG as of Q3 2023,with 80 LMICs procuring the product62%on DTG-Based Regimensamong CLHIV on pediatric treatment backbones in 2022(estimates from CHAI analysis based on da

19、ta from 17 LMICs)Generic pALDfrom Aurobindo and Viatris grantedtentative US FDA approval for CLHIV 3mo,6-24.9 kg;negotiated prices of US$14.85 and US$15.00 per 180-pack,respectively 40 Countriesinclude the dual HIV/syphilis test in national policyfor either pregnant women or key populations50%Increa

20、se in POCearly infant diagnosis(EID)test salesbetween 2021 and 20228.6M CD4 Testsrun in 2022,30%of which wereestimated to be run on point-of-care(POC)devicesOnly 46%of PLHIVwho developed TB in 2021 werereceiving ART,highlighting a critical gap75%Increase in 5FC and51%Increase in L-AmBorder volumes b

21、etween 2021 and 2022as seen by the APWG and driven by the Unitaid-CHAI Optimal project 91%on DTG-Based Regimensamong adults on ART in generic-accessible LMICs in 2022PEPFAR Procuring DRV/r(400/50 mg)and is expected to discontinue procurement of LPV/r(200/50 mg)Long-ActingLenacapaviradministered semi

22、-annually with a dailyoral optimized background regimenapproved by the US FDA for adults with multi-drug resistant HIV;no genericlicensing limits access in LMICs 10 LMICsapproved CAB-LA for PrEP,thoughcost and production capacity remain barriers to accessFlatlining POC VL Test Salesindicates a gap i

23、n testing for priority populations,such aspregnant and breastfeeding women,CLHIV,and peoplewith AHD or OIs 91%on DTG,and 180-count packs of TLD cost less than US$45 PPPY pDTG had the shortest regulatory approval on record for a generic HIV product,and is now used by 160,000 CLHIV in GA LMICsTREATMEN

24、TDIAGNOSTICSPREVENTIONADVANCED HIV DISEASE An HIVST is now available at US$1 per test,expanding opportunities for use Multiple point-of-care options now available for CD4,viral load,and early infant diagnosis testing Over 2.5 million individuals globally receiving oral PrEP Long-acting cabotegravir,

25、an injectable form of PrEP administered every two months,is approved for use in 10 LMICs,however access issues persist AIDS-related deaths fell nearly 70%and 20.8 million deaths were averted in the past 20 years Increased focus on AHD with optimal products now availableCLINTON HEALTH ACCESS INITIATI

26、VE6regulatory approval on record for a generic HIV product,160,000 children are already accessing pediatric DTG(pDTG)at a cost of approximately US$100 PPPY,partly as a result of pricing agreements negotiated by Clinton Health Access Initiative(CHAI)and partners.2,iv,v,vi,vii,viii However,despite the

27、se successes,some gaps in treatment remain,including slower scale-up of fixed-dose-combination(FDC)darunavir/ritonavir(DRV/r)in second-line treatment and retention of PLHIV in care.As the number of people on treatment increases and prices reduce,the ARV market in GA LMICs remains robust with an esti

28、mated US$1.9 billion market size in 2022 based on CHAI calculations of the annual cost of regimens in-use.iiiIn tandem with advances in treatment optimization,improvements in testing have further expanded access to HIV services.Today,laboratory diagnostics are increasingly decentralized with multipl

29、e point-of-care (POC)options for CD4,viral load(VL),and early infant Access to and quality of HIV services continues to improve,but critical gaps remain across the cascade Today the HIV response is markedly different from that of two decades ago.When the US launched the US Presidents Emergency Plan

30、for AIDS Relief(PEPFAR)in 2003,globally over 2.5 million people contracted HIV each year and two million people living with HIV(PLHIV)died annually.i,ii Exorbitantly priced antiretroviral therapy(ART)was inaccessible to individuals living in lower resource settings.In sub-Saharan Africa(SSA),one of

31、the regions most impacted by the epidemic,child mortality tripled and life expectancy dropped 20 years.ii Since 2003,innovative partnerships between governments,PEPFAR,the Global Fund,and other global partners have significantly improved access to HIV services across the cascade of care Figure 1.Thi

32、s was in large part enabled by the development of affordable,generic antiretrovirals(ARVs).Today,a generic version of dolutegravir(DTG)is used by over 90 percent of adults in generic accessible(GA)low-and middle-income countries(LMICs)and is available for less than US$45 per person per year(PPPY).1,

33、iii,iv Following the shortest FIGURE 1:ADVANCES IN HIV SERVICES ACROSS THE CASCADE AS OF OCTOBER 2023 1 See Appendix C for a definition of generic-accessible2 Child pricing based on 10-13.9 kg as the reference weight band GENERAL TRENDSIn the two decades since the establishment of PEPFAR and the Glo

34、bal Fund,new HIV infections have reduced by half and AIDS-related deaths decreased by nearly 70 percent.Further,HIV treatment is the most affordable it has ever been.In the HIV prevention,advanced HIV disease,and diagnostics spaces,novel and increasingly effective products hold potential for reducin

35、g new infections,mortality,and morbidity.Now,more than ever,is the time to double down on investments in HIV.To make continued progress towards ending HIV,global efforts must prioritize key populations and their partners,bridge treatment disparities between adults and children,and ensure sufficient

36、and sustainable funding,among others.2023 HIV MARKET REPORT7diagnosis(EID)testing.While HIV self-tests(HIVSTs)are now available at just US$1 each,uptake to date has been limited but is growing.ix While progress expanding HIV treatmentalongside more modest primary prevention effortshas contributed to

37、 reductions in HIV transmission,persistently high new HIV infection rates reinforce that treatment alone is insufficient to reach and maintain epidemic control.Global efforts increasingly prioritize effective combination prevention packages that include both socio-behavioral interventions,as well as

38、 highly effective biomedical interventions.In 2022,over 2.5 million individuals globally received oral pre-exposure prophylaxis(PrEP).i New options like injectable long-acting cabotegravir(CAB-LA)and future pipeline products have the potential to accelerate reductions in new HIV infections.However,t

39、he transformational potential of available long-acting products is currently limited by high costs and low production capacity.Targeted donor investment to accelerate generic development of promising long-acting PrEP products is crucial for achieving impact at scale.In the past 20 years,AIDS-related

40、 deaths have decreased by almost 70 percent,resulting in an estimated 20.8 million deaths averted.However,there were still 630,000 AIDS-related deaths in 2022 with tuberculosis(TB),cryptococcal meningitis(CM),and bacterial infections remaining the major causes of death among adults,and pneumonia,TB,

41、bacterial infections,diarrheal diseases,and severe acute malnutrition among the major causes of mortality for children.x,xi More work needs to be done to reduce the number of people presenting to care with advanced HIV disease(AHD),identify AHD sooner,and link individuals to treatment and prevention

42、 for opportunistic infections(OIs).For children living with HIV(CLHIV),urgent action is needed to further reduce AIDS-related mortality and morbidity.In 2022,CLHIV accounted for 13 percent of AIDS-related deaths,despite comprising only four percent of PLHIV.x Management of AHD in children is challen

43、ging.At least 30 percent of CLHIV present with severe immunosuppression at HIV diagnosis,and those who are hospitalized when they initiate ART have high mortality.xi A large portion of CLHIV are not on ART at all.In 2022,only 57 percent of CLHIV were on treatment compared to 77 percent of adults,an

44、unacceptable disparity Figure 2.Year-over-year,the gap between HIV treatment coverage for children and adults continues to grow.Due to these gaps in ART coverage,existing(but decreasing)use of less effective ARVs in pediatric populations,and various other contributing factors,less than half of CLHIV

45、 are virally suppressed,resulting in over 80,000 AIDS-related deaths among CLHIV in 2022.x To reduce these deaths,stepping up efforts to identify and treat pediatric AHD cases is crucial.FIGURE 2:HIV CASCADE FOR ADULTS AND CHILDREN LIVING WITH HIV,GLOBAL,2022XThese differences are even more pronounc

46、ed regionally,where 64 percent of children in East and Southern Africa(ESA)were on ART in 2022 compared to less than 40 percent in all other regions reporting data Figure 3.i These disparities often begin before a child is borndespite being home to 20 percent of pregnant women living with HIV,West a

47、nd Central Africa(WCA)accounts for 52 percent of pregnant women who are not on ART.x It is clear that a focus on case identification and treatment retention for both pregnant and breastfeeding women and children is imperative to close the pediatric HIV gap.FIGURE 3:PERCENTAGE OF CHILDREN LIVING WITH

48、 HIV RECEIVING ART BY REGION,2022iPLHIV who arevirally suppressedPLHIV on ARTPLHIV who knowtheir statusAdultsChildren86%77%71%63%57%46%East and Southern AfricaCaribbeanLatin AmericaWest and Central AfricaMiddle East and North Africa19%34%37%13%39%39%64%CLINTON HEALTH ACCESS INITIATIVE8funding,where

49、decreased revenue due to lockdowns and foreign debt obligations disproportionately impacted many of the countries with the highest HIV burdens.xiv A former trend of increasing domestic spending on HIV has since reversed post-COVID-19 pandemic,with two percent less domestic funding available for HIV

50、programs in 2022 compared to 2021,the third consecutive year of decreases.x Factors such as stigma,discrimination,and social barriers can also hinder the effective allocation and utilization of funds.Key populations(KPs)remain one of the most underfunded areas in the HIV response,with a 90 percent f

51、unding gap for prevention programs estimated in 2022 compared to what is needed to reach 2025 targets in LMICs.xv,x Without urgent and collaborative action to ensure adequate and sustainable funding,the HIV epidemic will continue to have health,social,and economic costs disproportionally impacting k

52、ey and priority populations,thereby deepening inequality.Crucial to these efforts will be continued support for ending HIV via the Global Fund and PEPFAR,among others.Ensuring a sustainable HIV response will require a range of strategies to enhance financing for the health sector as a whole and maxi

53、mize the use of existing resources and partnerships.Overcoming political and social barriers remains critical to sustaining and expanding the HIV response,especially among key populations Stigma,discrimination,and criminalization of key populations are also significant barriers to achieving the goal

54、s of the HIV response.As a result,key Ongoing funding and resource mobilization threats could hamper continued progress toward epidemic controlInternational and domestic funding has been crucial to the success of the HIV response over the past 20 years.However,recent funding threats and reductions i

55、n HIV investments put these hard-won gains at risk.For example,the PEPFAR program represents the largest investment by a country toward a single disease area,contributing over US$110 billion to end HIV while simultaneously strengthening global health and economic security in 50 countries over the pa

56、st 20 years.ii In Sep.2023,the program was due for its fourth five-year reauthorization.However,politicization has put the traditionally bipartisan program in peril and reauthorization is not certain.A failure to reauthorize PEPFAR risks lives and the forward momentum needed to address remaining gap

57、s and eliminate HIV as a public health threat.xii Looking across all funding for HIV programs in LMICs,in 2022,a total of US$20.8 billion was provided representing a 2.6 percent decrease from 2021s funding envelope.This continues a years-long pattern of stagnant and decreasing funding Figure 4.x Int

58、ernational organizations,governments,and other donors have played a crucial role in providing financial support to HIV programs in LMICs,and continued investment,including PEPFAR reauthorization and meeting the US$2 billion gap in Global Fund targets while also fulfilling the pledges of the seventh

59、Global Fund replenishment,is imperative for reaching global targets on time.xiiiSignificant challenges remain in ensuring sufficient and sustainable funding for HIV programs.Global economic challenges,competing health concerns,and shifting global priorities have impacted funding availability.This wa

60、s particularly the case for domesticFUNDING(USD)0$5B$10B$15B$20B Other internationalGlobal FundUS bilateralDomestic public and private2022202120202019201820172016201520142013201220112010FIGURE 4:FUNDING FOR HIV IN LMICs BY SOURCE,2010-2022x2023 HIV MARKET REPORT9populations continue to be among the

61、most at risk for HIV transmission,have a higher prevalence of HIV,and lower treatment coverage when compared to the general population in most countries.x Currently,64 countries criminalize same-sex relationships,and half of these are located in Africa with the death penalty possible in Mauritania,N

62、igeria,Somalia,and Uganda Figure 5.xvi In countries where these relationships remain criminalized,a study in SSA found HIV prevalence among men who have sex with men was five times higher.xvii While some countries are exploring decriminalization,others such as Ghana,Iraq,Kenya,and Tanzania are pursu

63、ing harsher penalties,with Uganda recently passing a sweeping anti-lesbian,gay,bisexual,transgender,queer or questioning(LGTBQ)law.xvi FIGURE 5:CRIMINALIZATION OF SAME-SEX RELATIONSHIPS BY REGION,2023xviCriminalization of key populations can also negatively impact the ability of governments and part

64、ners to provide necessary HIV services to those in need.In Uganda,PEPFAR reported significant drops in weekly attendance by KPs at drop-in-centers providing HIV treatment and prevention services while the Anti-Homosexuality Act was debated in parliament.This attendance has not recovered in all cente

65、rs despite interventions to improve client access.xviii Rising rates of new infections in some regions such as Asia and the Pacific and the Middle East and North Africa,primarily driven by infections among KPs and their partners,further point to the need for KP-friendly services and enhanced efforts

66、 to reduce stigma and discrimination.x Global partners are doubling down on their commitments to priority populations,as outlined in PEPFARs new five-year strategy.Released in 2022,the strategy aims to end HIV as a public health threat by 2030 while prioritizing evidence-based interventions,improvin

67、g health equity,and sustainably strengthening public health systems Figure 6.ii However,the ability to implement this strategy precariously hinges on congressional approval of the next five-year reauthorization of PEPFAR,threatening progress and putting lives at risk.FIGURE 6:PILLARS OF PEPFARS NEW

68、FIVE-YEAR STRATEGYiiComorbidities among PLHIV negatively impact HIV outcomes,suggesting opportunities for health services integration Due to affordable and effective treatment,PLHIV are living longer.Data from a US study found that PLHIV who are diagnosed and treated when CD4 counts are high,maintai

69、n adherence to ART,and have access to medical care can anticipate a life expectancy mirroring the general population.xix With these improvements in life expectancy come chronic comorbidities such as diabetes and hypertension that commonly affect aging populations.However,for many in LMICs,care for n

70、on-communicable diseases(NCDs)is often inaccessible.NCDs can complicate HIV treatment and increase morbidity and mortality in PLHIV.Deaths among PLHIV due to causes other than AHD doubled from 14 percent in 2010 to 32 percent in 2022.x Recognizing the evolving health needs of PLHIV,in 2023 the World

71、 Health Organization(WHO)released implementation 0 10 20 30 40 50 60 Non-CriminalizationCriminalizationOceaniaEuropeAsiaAmericasAfricaCOUNTRIES2650182655662032HEALTH EQUITY FOR PRIORITY POPULATIONS SUSTAINING THERESPONSE PUBLIC HEALTHSYSTEMS AND SECURITY FOLLOW THE SCIENCE=TRANSFORMATIVEPARTNERSHIPS

72、 CLINTON HEALTH ACCESS INITIATIVE10A recently published WHO technical brief recommends integrating psychosocial and HIV services for adolescents and young adults,identifying best practices and strategic actions to support healthy behaviors and bolster mental health.This brief aims to ensure the well

73、being of this important demographic group during a crucial developmental stage in life.xxv However,despite a strong research base of effective,low-cost mental health interventions appropriate for LMIC settings,there are large gaps in translating research into practice.xxvii While it is crucial to ta

74、ckle the substantial comorbidity between HIV and mental health,it is important to pave the way for broader mental health integration to diminish stigma and enhance overall health outcomes beyond PLHIV.Syphilis and hepatitis B remain common co-infections that particularly impact pregnant women and ch

75、ildren.HIV is known to interact with both syphilis and hepatitis B to increase mother-to-child transmission risk,underscoring the need for integrated diagnostics and care for these diseases to improve maternal and neonatal health outcomes.This is especially true in SSA,where the burden of these dise

76、ases is the highest.Unequal funding across diseases has impeded efforts to reduce syphilis and hepatitis B infection,with a recent assessment in ten SSA countries showing a gap between HIV and syphilis screening coverage of between five and 52 percent.Newly approved dual HIV/syphilis tests and tripl

77、e combination diagnostic tests under development have the potential to close this gap,link more women to treatment,and accelerate the triple elimination agenda when paired with differentiated service delivery models.xxviiiguidance outlining a holistic approach for integrating NCD prevention and cont

78、rol into HIV,TB,and sexual and reproductive health(SRH)programs.xx Mental health is another neglected health concern that disproportionally impacts and leads to poor outcomes among PLHIV.Poor mental health increases the risk of acquiring HIV four-fold and worsens treatment outcomes.xxi Following dia

79、gnosis,PLHIV are 100 times more likely to die by suicide than the general population.xxii The prevalence of depression in PLHIV in sub-Saharan Africa is estimated at 24 percent,compared with less than three percent for the general population.xxiii Adolescents with HIV are particularly impacted by po

80、or mental health.Globally,there are 3.2 million adolescents and young adults living with HIV between 15 and 24 years of age,and evidence shows that this group has higher rates of mental health challenges than their HIV-negative peers.xxiv Among adolescent key populations,poor mental health is exacer

81、bated by multiple stigmas including their youth,minority group association,and HIV status.xxv Between 2010 and 2020,HIV-associated mortality declined at a slower pace in adolescents than in children,with a 37 percent reduction in mortality among PLHIV 10 to 19 years as compared to 60 percent among t

82、hose aged zero to nine years Figure 7.xxvi This limited progress highlights the need for more support to ensure adequate and holistic care for this population.FIGURE 7:REDUCTIONS IN GLOBAL AIDS-RELATED DEATHS AMONG CHILDREN(0-9 YEARS)AND ADOLESCENTS(10-19 YEARS),2010-2020 xxvi37%CHILDREN0-9 YearsADO

83、LESCENTS10-19 Years60%Reduction inAIDS-relateddeathsReduction inAIDS-relateddeaths2023 HIV MARKET REPORT112022 saw the lowest number of new HIV infections in three decades,however,year-over-year reductions are still too low to meet the global target of ending AIDS by 2030.Despite global progress,dis

84、parities across populations persist and some regions are seeing an alarming increase in new infections.Increased access to effective primary prevention interventions,particularly among those at highest risk of HIV acquisitionincluding key populations,adolescent girls and young women,and pregnant and

85、 breastfeeding womenwill be essential for reducing HIV incidence.Long-acting cabotegravir and other novel prevention products have the potential to enhance user choice,increase uptake and promote effective use,and significantly reduce new HIV infections.However,access barriers such as affordability

86、and generic production capacity must be addressed to realize transformational impact.Key populations and their partners continue to account for a disproportionate number of new infections,and these populations often lack access to tailored and stigma-free prevention services.Further,discriminatory l

87、aws,violence,and stigma continue to pose barriers.x Ultimately,these disparities in access are human rights issues,and underscore the importance of integrating human-rights-based approaches into the HIV response to achieve meaningful progress in reducing new infections.Despite generic licensing for

88、CAB-LA,major access challenges persist requiring urgent action to accelerate generic developmentIn Dec.2021,the United States Food and Drug Administration(US FDA)approved long-acting cabotegravir,a highly effective injectable PrEP administered every eight weeks,for use in adults and adolescents at r

89、isk of HIV acquisition and weighing at least 35 kg.xxix CAB-LA is the first long-acting injectable HIV prevention product on the market,but LMICs continue to face major access challenges.Following strong community advocacy for rapid,equitable,and affordable access to CAB-LA,ViiV Healthcare signed a

90、voluntary license agreement with the Medicines Patent Pool(MPP)in July 2022.xxx,xxxi Subsequently,in March 2023 ViiV and MPP announced sublicense agreements with Aurobindo,Cipla,and Viatris to manufacture generic CAB-LA for use in 90 countries.xxxii PREVENTIONProgress in HIV prevention is unequal ac

91、ross populations and geographiesIn 2022,there were an estimated 1.3 million new HIV infections globally,the lowest number in the past three decades.However,the global response remains off track from the UNAIDS 2025 target of 370,000 infections.x Further,there are disparities in the distribution of a

92、nd progress in reducing new HIV infections across regions,sub-national geographies,and populations.For example,while SSA saw large reductions in HIV infections between 2010 and 2022,women and girls continue to bear a disproportionate burden of new infections in the region,representing 63 percent of

93、all new HIV infections in 2022.However,less than half of the districts in high HIV incidence areas have HIV prevention programs for adolescent girls and young women(AGYW).Beyond SSA,HIV prevention progress is slower.Several regions,including Asia and the Pacific and Eastern Europe and Central Asia s

94、aw steady or increasing numbers of new infections from 2010 to 2022 Figure 8.x FIGURE 8:CHANGE IN NEW HIV INFECTIONS BY REGION(2010-2022)AND NUMBER OF NEW INFECTIONS(2022)x-60%-40%-20%020%40%60%80%MENAEECALAAPCaribbeanWCENAGlobalWCAESAPERCENT CHANGE IN HIV INFECTIONS FROM 2010 TO 2022NUMBER OF NEW H

95、IV INFECTIONS(2022)500K160K1.3M58K16K300K110K160K17K-57%-49%-38%-23%-15%-14%8%49%61%CLINTON HEALTH ACCESS INITIATIVE12use of long-acting HIV prevention and treatment regimens.xxxvi It is important to note,however,that even if partners,manufacturers,and ministries were to implement these roadmap reco

96、mmendations,generic CAB-LA availability is likely several years away.Research indicates potential for three-month CAB-LA dosing among cisgender women,but continues to highlight testing challengesRegulatory approval of CAB-LA for PrEP is largely based on the large-scale HPTN 083 and 084 clinical tria

97、ls,which demonstrated CAB-LAs statistical superiority over daily oral TDF/FTC for HIV prevention.xxxvii While more research is needed to understand choice and preferences in real-world settings,the open label extensions of both efficacy studies continue to show strong preferences for long-acting inj

98、ectable PrEP.Among adult cisgender women enrolled in HPTN 084,78 percent opted for CAB-LA over oral TDF/FTC in the choice period.xxxviii Similarly,among African cisgender Until generic CAB-LA is available,ViiV remains CAB-LAs sole supplier,impacting available volume and affordability.While CAB-LA ha

99、s been approved in ten LMICs(Brazil,Botswana,Malawi,Malaysia,Nigeria,Peru,Philippines,South Africa,Zambia,and Zimbabwe)as of Oct.2023,these supply constraints continue to represent a challenge for introduction planning.xxxiii In the near term,access will be limited outside of implementation projects

100、,planned PEPFAR procurement in Malawi,Ukraine,Vietnam,Zambia,and Zimbabwe,and modest volumes expected to be available through the Global Fund.xxxiv Communities continue to advocate for accelerated generic CAB-LA development,however,as of Oct.2023,no confirmed donor investment had been announced.Leve

101、raging decades of product introduction experience and input from partners,CHAI created an innovative roadmap outlining potential steps to accelerate generic CAB-LA development and equitable introduction Figure 9.xxxv This roadmap was released as part of a special issue publication on theRoadmap Acce

102、ss ObjectivesPartner Coordination and Alignment:Ensure coordination and alignment across partners,avoiding redundancy experienced during oral PrEP introductionGeneric Development:Incentivize accelerated,efficient generic product development through a combination of evidence-based and innovative mark

103、et-shaping interventionsNational Program Preparation:Provide targeted support to maximize CAB-LA impact based on health system readiness assessments,including development of national policies,guidelines,and introduction plans and tools;system strengthening;quantification and procurement;and evidence

104、 generationCommunity Engagement:Support community engagement,ensuring that demand generation and delivery approaches for CAB-LA are person-centered and community-ledRegulatory Strategy:Expedite reviews by regulatory authorities and national medicines regulatory authorities to minimize time to market

105、US FDA APPROVAL OF CAB-LA FOR PrEPEFFICACY TRIALSPHASED IMPLEMENTATIONCAB-LA VOLUNTARY LICENSEREGULATORY SUBMISSION FOR GENERIC CAB-LAEvidence Generation with OriginatorScale up with Generic CAB-LACAB-LA USETimeDEC 2021JUL 2022Significant delays between US FDA regulatory approval and generic develop

106、ment anticipatedFIGURE 9:CAB-LA FOR PrEP ROADMAP AND ACCESS OBJECTIVESxxxv2023 HIV MARKET REPORT13female adolescents,CAB-LA was tolerable and preferred as compared to daily oral PrEP.xxxix Recent pharmacokinetic data shows protective levels of CAB-LA persist for three months in cisgender women,which

107、 could open the window for a future dosing indication that aligns with injectable contraception,reduces delivery costs,and results in fewer clinic visits.xl Analysis of the positive predictive value of single rapid HIV tests in HPTN 084 found higher rates of false positives among CAB-LA users.Howeve

108、r,two rapid HIV tests were sufficient to confirm HIV diagnosis and recommend treatment initiation.Based on these results,HIV programs will need to ensure appropriate testing strategies for CAB-LA,potentially including further testing to confirm diagnosis and additional client counseling where testin

109、g strategies may differ from other PrEP options.xli Notably,a review of the small number of incident HIV infections recorded during the HPTN studies found that the use of CAB-LA for PrEP led to viral suppression and delayed or diminished antibody expression that can persist for months after infectio

110、n,a condition dubbed“long-acting early viral inhibition”(LEVI).As a result,HIV rapid tests and antigen tests fail to detect infection in a timely manner.While the cases were rare,these missed diagnoses have the potential to increase the risk of integrase strand transfer inhibitor(INSTI)resistance.xl

111、ii Ongoing investigations are exploring testing approaches needed in the context of LEVI.The use of RNA testing for HIV screening could help identify and confirm infections earlier in some cases,but would be expensive for prevention programs and would introduce additional complexity for CAB-LA initi

112、ation and continuation,potentially resulting in lower PrEP coverage during periods of elevated risk.xlii Given its proven high efficacy and the potentially limited value of adding RNA screening to testing algorithms,WHO guidelines note that CAB-LA should still be considered for HIV PrEP in settings

113、where HIV RNA screening is not readily available.xliiiAn increasing global focus on user choice drives research and investments in the HIV prevention pipelineSeveral implementation studies are underway to explore real-world delivery and demand generation approaches for PrEP products,including CAB-LA

114、,the dapivirine vaginal ring(DVR),and oral PrEP.The Biomedical Prevention Implementation Collaboratives Integrated Study Dashboard details these implementation studies across geographies,populations,and projects.xxxiv Evidence generated from these studies aims to fill important implementation knowle

115、dge gaps,such as questions about real-world product choice,feasibility across service delivery channels,integration with other services,and the optimal combination of prevention methods and other services for specific populations.The impact of the growing portfolio of prevention products will depend

116、 on their accessibility,affordability,and integration within systems that fully consider the social and political context in which HIV infections take place.A person-centered,choice-based approach will be crucial to ensure efforts are community-led and that prevention strategies better align with th

117、e unique circumstances and lived experiences of at-risk populations.Oral PrEP initiations continue to grow,with new research on effectiveness among cisgender women and opportunities to optimize PrEP deliveryIn 2022,approximately 1.9 million people in LMICs received PrEP.While many prevention program

118、s are now rapidly increasing oral PrEP initiations,PrEP provision in LMICs is still limited to a small number of countries and is heavily concentrated in ESA Figure 10.i While most new HIV infections occurred in ESA in 2022,approximately a quarter occurred in Asia and the Pacific,where there is sign

119、ificantly lower PrEP coverage.National programs in these regions have an opportunity to address this disparity by scaling oral PrEP use among at-risk populations.xFIGURE 10:NUMBER OF PEOPLE IN LMICs WHO RECEIVED ORAL PREP IN 2022i0300K600K900K1.2M1.5MMENAEECAAPLACWCAESA9.58.98.19.39.69.79.8NUMBER OF

120、 PEOPLE ON ORAL PREP IN 20221.3M437K100K98K12K1KCLINTON HEALTH ACCESS INITIATIVE14VMMC continues to be a cost-effective prevention intervention in SSASince 2007,voluntary medical male circumcision(VMMC)has been a WHO-recommended,cost-effective prevention strategy in countries with high HIV prevalenc

121、e and low coverage of male circumcision.xlix However,as ART coverage expands and additional prevention options are made available,there has been renewed interest in evaluating the long-term cost effectiveness of VMMC.Researchers recently modeled scenarios to better understand the impact of changing

122、epidemic conditions,including reductions in HIV incidence,on the cost-effectiveness of VMMC.Across five mathematical models,researchers found VMMC provides cost-savings over 50 years,while also lowering HIV incidence and mortality rates in men aged 15-49 in Malawi,South Africa,and Zimbabwe.l With co

123、ntinued improvements in HIV treatment and prevention,including the introduction of highly effective long-acting PrEP products,further modelling may be needed.Given the widening funding gap in the global HIV response,the development of efficient service delivery and demand generation models,and their

124、 integration within routine health services,will be crucial to minimize the cost of delivering VMMC services and enhance accessibility.Trends in vertical transmission of HIV indicate additional efforts are needed to strengthen existing programs and expand PrEP optionsSince 2015,ART coverage among pr

125、egnant and breastfeeding women has plateaued around 80 percent.In the same period,HIV infections among children aged zero to 14 years has slowed,from 200,000 in 2015 to 130,000 in 2022.This stagnation is particularly acute in certain regions,such as WCA,where vertical transmission programs reached o

126、nly 53 percent of pregnant and breastfeeding women in 2022.Globally,and specifically in WCA,lack of access to ART during pregnancy or breastfeeding was the highest contributor to new HIV infections in children Figure 12.These findings suggest additional effort is needed to identify and link pregnant

127、 and breastfeeding women to treatment,via facility and community-based case finding,and retain them on ART through the end of breastfeeding.x Previous studies have demonstrated that daily oral TDF/FTC is more than 99 percent effective for HIV prevention among men and transgender women who have sex w

128、ith men.However,past findings indicate oral PrEP effectiveness may be lower for cisgender women,potentially due to poorer adherence and/or biological differences.xliv Data from a recent pooled analysis of over 6,000 cisgender women on TDF/FTC supports the real-world effectiveness of oral PrEP in cis

129、gender women with consistent adherence(defined as at least four doses per week),indicating that it may be as high as other populations Figure 11.However,over half of all participants did not use TDF/FTC consistently,highlighting the urgent need for additional prevention options that improve adherenc

130、e,such as long-acting modalities.xlv FIGURE 11:HIV INCIDENCE RATES AMONG WOMEN WITH AVAILABLE ORAL PREP ADHERENCE DATAxlv Additionally,efforts are underway to optimize oral PrEP delivery.In Kenya,researchers found that six-month oral PrEP dispensing and semiannual clinic visits resulted in non-infer

131、ior adherence compared to the standard quarterly dispensing and visit schedule.Additionally,the use of HIV self-tests every three months was non-inferior to clinic-based testing.xlvi This differentiated service delivery model has the potential to optimize oral PrEP delivery and further reduce HIV in

132、cidence.PrEP-specific funding is essential for increasing uptakeAnalysis shows that earmarked funding for PrEP is crucial for driving increased uptake.Targeted PrEP investments are likely to continue to play a major role in defining the future prevention landscape.xlvii In Sep.2022,the Global Fund c

133、ollaborated with the Childrens Investment Fund Foundation(CIFF)to establish a catalytic matching fund of US$33 million to drive the scale-up of PrEP,including introducing novel PrEP options,in Kenya,Mozambique,Nigeria,South Africa,Uganda,and Zambia.xlviii 00.51.01.52.02.53.03.5Consistently LowHigh,b

134、ut DecliningConsistently HighConsistently Daily9.58.98.18.99.39.49.69.79.8HIV INCIDENCE PER 100 PERSON YEARSEstimate00.130.491.2795%Confidence Interval7 tablets per week4-6 tablets per week2 tablets per week2-3 tablets per week2023 HIV MARKET REPORT15FIGURE 12:CAUSES OF HIV INFECTIONS IN CHILDREN,GL

135、OBAL AND IN SUB-SAHARAN AFRICAxA recent study co-authored by CHAI used a mathematical model to determine the most cost-effective combination of interventions to prevent vertical transmission among pregnant and breastfeeding women in Zambia over a 12-month period.Results showed that the interventions

136、 with the greatest reduction in vertical transmission included maternal support groups(35 percent reduction in infant infections),HIV retesting(6.5 percent reduction in infant infections),and infant prophylaxis(4.5 reduction in infant infections).li Women are at substantially higher risk of acquirin

137、g HIV during pregnancy and the post-partum period,indicating the importance of access to combination prevention.lii Among the limited number of PrEP studies that have included pregnant women,several reinforce the safety of PrEP products for this population and their children.Recent results from a si

138、ngle-site study in South Africa confirm oral PrEP(TDF/FTC)use by pregnant women is not associated with preterm birth or small-for-gestational-age infants.liii An extension study in Kenya also found that children exposed to oral PrEP during pregnancy did not have reduced bone density or stunted growt

139、h as compared to unexposed infants at 36 months.liv These results support existing WHO guidelines encouraging the use of oral PrEP in pregnant and breastfeeding women at increased risk of HIV as part of a combination prevention approach.lv Two phase 3b open-label studies involving the dapivirine vag

140、inal ring,a flexible self-inserted silicone ring for HIV PrEP,reinforced the rings safety during pregnancy and breastfeeding.DELIVER,a randomized safety trial carried out among pregnant women in Malawi,South Africa,Uganda,and Zimbabwe,found the ring was equally safe to use in the third trimester of

141、pregnancy as daily oral TDF/FTC.lvi DELIVERs companion study,B-PROTECTED,revealed women can also safely breastfeed while using the ring.B-PROTECTED found very low levels of dapivirine in participants breast milk and even lower concentrations in infants blood,posing no safety risk.lvii A sub-study of

142、 HPTN 084 will also explore the impact of CAB-LA for PrEP on pregnant and breastfeeding women and their children following an open-label extension amendment removing a requirement for contraception use during the study.lviii Data from close monitoring of women in the blinded phase of trial who becam

143、e pregnant show that residual cabotegravir was well tolerated and may be safe during pregnancy and breastfeeding.lix In the open-label extension,women will be provided the option of continuing CAB-LA throughout their pregnacy,which will generate further safety data.lviiiWHO guidance emphasizes that

144、women of reproductive potential should not face barriers to effective PrEP options such as CAB-LA.xliii In Kenya and South Africa,oral PrEP-experienced pregnant and postpartum women expressed preference for long-acting injectable PrEP over other modalities,demonstrating potential acceptability among

145、 a priority population.lx Similar findings from an HPTN 084 sub-study also signalled preference for CAB-LA over oral PrEP among women who were pregnant or intended to become pregnant.lxi The above research indicates prenatal and postnatal services may represent appropriate integration opportunities

146、for PrEP services,though additional implementation and safety research is needed.As countries update national guidelines to include CAB-LA and develop introduction plans,it is imperative they are inclusive of women of reproductive potential or those who are pregnant or breastfeeding.The HIV preventi

147、on pipeline includes investigational products with novel delivery mechanisms and MPTs set to increase PrEP optionsTo meet the diverse needs of at-risk populations,research is underway to better understand the needs and demands of potential end users.A dynamic and robust pipeline of novel HIV prevent

148、ion products has the potential to increase user choice and expand the prevention market by delivering easier to use,more tolerable,and discreet products.The section below features several HIV prevention products currently in development:20%40%60%80%100%WCAESAGlobalPERCENTMother was on ART but did no

149、t achieve viral supression12K29K65K27K8.6K17K17K17K2.2K34K6.1KMother acquired HIV during pregnancyMother did not continue ART during pregnancy or breastfeedingMother did not receive ART during pregnancy or breastfeeding8.5KCLINTON HEALTH ACCESS INITIATIVE16with one to three months of protection.Buil

150、ding on previous user research from South Africa and Uganda,a recent early-stage product development assessment in Kenya found MAPs were acceptable across stakeholder groups,including adolescent girls and young women,female sex workers,men who have sex with men,service providers,and policy makers.lx

151、ix FIGURE 13:MICROARRAY PATCH DRUG DELIVERY SYSTEM EXAMPLElxx SUPPOSITORIES:New data from a pair of phase 1 trials show that a rectal/vaginal suppository combining the antiretrovirals TAF and elvitegravir is safe in humans,with high concentrations of drug present in rectal and vaginal tissues over t

152、he course of 24 hours.lxxi,lxxiiIMPLANTS:Qualitative end-user research from South Africa indicates potential acceptability of a long-acting,implantable form of PrEP by clients and providers.lxxiii All subdermal forms of HIV PrEP are currently in preclinical stages of development and are likely years

153、 away from availability.BROADLY NEUTRALIZING ANTIBODIES:Long-acting,injectable broadly neutralizing antibodies(bNAbs)are being explored for HIV prevention in a range of populations and may offer a particularly promising intervention during the breastfeeding period for HIV-exposed infants.However,out

154、standing questions on LenacapavirIn Dec.2022 the US FDA approved lenacapavir(LEN)in combination with other ARVs for the treatment of people with multi-drug resistant HIV.lxii This capsid inhibitor is also being studied as a twice annual subcutaneous injection for HIV prevention.PURPOSE 1 is a two-pr

155、onged study that aims to evaluate the efficacy of LEN as well as tenofovir alafenamide fumarate/emtricitabine(TAF/FTC)for HIV PrEP in AGYW at risk of HIV infection.TAF/FTC is an oral PrEP product that is currently only approved for use in men.Initial results from this study are expected in 2024.lxii

156、i The PURPOSE 2 study is evaluating the efficacy of LEN for HIV PrEP in men who have sex with men,with primary results expected in 2025.lxiv Dual Prevention PillThere are several multipurpose prevention technologies(MPTs)under development that combine contraception with HIV PrEP.If successful,such M

157、PTs have the potential to offer benefits such as reducing pill/product burden,improving motivation and adherence,reducing stigma,and accelerating service delivery integration.lxv Viatris is currently developing a novel dual prevention pill(DPP)for the prevention of pregnancy and HIV.The co-formulate

158、d daily pill will be packaged in a 28-pill blister pack with 21 pills containing TDF,FTC,levonorgestrel,and ethinyl estradiol,and seven pills containing only TDF/FTC.Viatris is tentatively expected to submit the DPP for regulatory review to the US FDA in 2024.lxvi Clinical cross-over acceptability s

159、tudies using an encapsulated combination pill began in late 2022 in South Africa and Zimbabwe to compare adherence,acceptability,and preference to separate oral PrEP and contraception pills.A follow-up version of this study will also be conducted once co-formulation is complete.lxvii A recent cost-e

160、ffectiveness study co-authored by CHAI indicates that among women not already using PrEP,the DPP is likely to be cost saving in sex workers and serodiscordant couples,though further studies on real-life adherence are needed.lxviii Other Novel Delivery ModalitiesMICROARRAY PATCHES:Microarray patches(

161、MAPs)are a novel platform being developed for the delivery of ARVs,which may be co-formulated with hormonal contraception for certain populations Figure 13.MAPs offer an easy,discreet,self-administered option Stratum CorneumEpidermis2023 HIV MARKET REPORT17cold chain requirements and duration of eff

162、icacy could impact utility in resource-limited settings.Researchers modeled various scenarios and found bNAb product characteristics would ideally include a three-month or longer duration of effect,cost US$60 or less per dose,and have efficacy of at least 50 percent to be cost effective for use in i

163、nfants in SSA.lxxiv Results from the Antibody Mediated Prevention(AMP)Trials found that a bNAb(VRC01)tested did not prevent HIV among cisgender men and transgender persons in the Americas and Europe and at-risk women in SSA.However,in HIV isolates sensitive to the bNAb used in the trial,prevention e

164、fficacy was shown to be 75 percent.lxxv Further investigations of bNAbs informed by the results of the AMP trials continue in a range of early phase,pre-drug studies.lxxvi,lxxvii,lxxviii VACCINES:In Jan.2023,the Mosaico study,a large phase 3 HIV vaccine efficacy study,was stopped due to high HIV inc

165、idence in the trial arm.lxxix This is the third vaccine efficacy study to conclude early since 2020.While the early termination of Mosaico represents a setback for vaccine research,several innovative technologies are under investigation,including an experimental protein nanoparticle and a DNA/protei

166、n/modified virus combination vaccine.lxxx PrEPVacc,an African-led prevention study,is currently testing the efficacy of the combination vaccine.lxxxi Additional African-led vaccine efforts include the Multisite Adolescent Girls and Young Women study based in Zambia.Supported by the International AID

167、S Vaccine Initiative,this program will collect and analyze a wide range of data from AGYW volunteers to inform the development of HIV vaccine and antibody products.lxxxiiCLINTON HEALTH ACCESS INITIATIVE18several other more aggressive forecasts including one where HIVST becomes the predominant testin

168、g modality in non-ANC settings.FIGURE 14:EIC HIV TESTING PRODUCT MIX FORECAST IN DONOR FUNDED LMICs-CURRENT APPROACH SCENARIOlxxxvThis expansion in HIVST is expected to be facilitated by the increased availability of lower-cost options:currently,there are several HIVSTs available under US$2(EXW)per

169、test.Further,the Wondfo HIVST,the newest and lowest cost option,is available at just one US dollar per test thanks to a ceiling price agreement with MedAccess.ix In Oct.2023,Uganda formally adopted the Wondfo HIVST and the first shipment is expected to arrive in Nov.2023.lxxxvi,xcvii Other countries

170、 are currently pursuing regulatory approval.There are also two HIVSTs currently in WHO prequalification(PQ)review,with both expected to be priced less than US$2(EXW).These tests,the Sedia Asante oral fluid HIVST and Premiers First Response HIVST(blood-based),could potentially be available as early a

171、s the end of 2023.TESTINGRates of HIV status awareness are stagnating,but data show testing services remain a critical pathway for engagement in the HIV cascade of care In 2022,86 percent of PLHIV globally knew their HIV status,only a two percentage point increase compared to 2021.i Certain populati

172、ons also continue to fall behind,with testing rates for children and adolescents significantly below those of adults.x As the global community pushes toward the last mile in HIV diagnosis,those who remain unaware of their status will likely be the hardest and most expensive to reach.However,testing

173、services remain a critical part of a complex and often non-linear continuum of lifelong care,acting as a point of re-entry for clients who have disengaged from care,playing a vital and growing position as a gateway to prevention services,and performing a central role in monitoring within prevention

174、programs.Research shows that a significant number of people starting HIV treatment are actually re-initiating to care after a gap.In a review of ten studies across the Democratic Republic of Congo,Ethiopia,Kenya,and South Africa,between 20 and 50 percent of people who presented for ART initiation we

175、re found to be previously exposed to ART.lxxxiii This highlights the importance of testing as a primary entry point for re-engagement in care and reinforces the continuing need to maintain HIV testing volumes.Access to low-cost HIV self-tests continues to expand Adoption of HIV self-testing continue

176、s to pick up speed as 102 countries currently include HIV self-testing in national policies and 63 countries are implementing self-testing routinely.lxxxiv This represents a five-fold increase in the number of countries with routine HIV self-testing implementation compared to 2017.lxxxiv This growth

177、 is further reflected in a new HIV testing forecast from Eureka Idea Co.(EIC),which predicts considerable uptake of HIV self-testing even in the status quo scenario Figure 14.EIC also includes 50M100M150M200M250M20195MILLIONS OF TESTS95519.5202020212022202320242025202620279804651282478.916844019HIVS

178、TPrEP A1Non-ANC A1Dual HIV/Syphilis AIA2/A3ANC A1 (HIV only)8.198.92178536239.35218633269.47238833289.610268834299.712308934299.815HIV diagnosis remains the largest gap among the UNAIDS 95-95-95 targets despite the central role of HIV testing across the cascade of HIV care,including within preventio

179、n services.Price reductions for HIV self-tests and expanded use of combination tests could improve screening rates and catalyze service integration.Persistent gaps in early infant diagnosis testing continue to delay progress toward epidemic control and contribute to inequities in outcomes for childr

180、en,although increasing sales volumes of point-of-care early infant diagnosis tests in 2022 provide a point of optimism.2023 HIV MARKET REPORT19countries,undiagnosed HIV prevalence decreases after age two,with more CLHIV dying than being diagnosed Figure 15.Identification during these initial years i

181、s critical as the study estimates that unless they are diagnosed and initiated on treatment,almost all children will die before the age of five.xcFIGURE 15:MODELED PERCENT OF CLHIV UNDER TWO YEARS OLD UNDIAGNOSEDxcFurther,while EID remains critical for finding infants with HIV,testing volumes have f

182、latlined over the past few years.In 2022,CHAI estimates that there was no change in EID testing volumes in LMICs compared to 2021,although challenges with POC reporting complicate forecasting Figure 16.3,xciIn addition to this overall stagnation,there are also concerning regional gaps in EID coverag

183、e.For example,in WCA,only 23 percent of HIV-exposed infants were tested for HIV by two months compared to 83 percent in ESA Figure 17.i Further,WCA shows a three-percentage point decrease from 2021,part of a three-year trend of decline.Persistent gaps in early infant diagnosis and pediatric testing

184、stall progress toward epidemic controlChildren and infants continue to be left behind in the HIV response across the care and treatment cascade,beginning with stagnating progress in identification of those living with HIV.Data from 16 PEPFAR countries,which represent 80 percent of CLHIV,found that c

185、ountries only met 17.6 percent of the estimated pediatric testing need.lxxxix This data reinforces the need for more testing through a strategic mix of testing modalities.A recent modelling study using data from Cte dIvoire,South Africa,and Zimbabwe projected that acrossExpansion of blood-based HIVS

186、T After a successful pilot among students at seven universities,Uganda has decided to further roll out a blood-based HIVST among peers of previous study participants pending pricing and procurement negotiations.lxxxvii Zambia has also successfully piloted and now adopted blood-based HIVST to provide

187、 clients with more testing options and leverage more affordable HIV self-test kits for expansion of secondary distribution at antenatal care(ANC)and community distribution through community-based volunteers.lxxxviiiSouth AfricaZimbabweCte dIvoire44%35%53%56%Actual/Forecasted DemandCoverageUnmet Need

188、2020202120222023202420251.5M1.9M1.9M2.1M2.4M2.6M3.5M100%80%60%40%20%2.5M1.5M0.5M0%1.0M2.0M3.0M202720262.7M2.8MEID TESTS RUNCOVERAGE3 Lack of supplier sales data disaggregated by quarter or country complicated POC forecasting in 2022.FIGURE 16:LMIC EID DEMAND FORECASTxciCLINTON HEALTH ACCESS INITIATI

189、VE20FIGURE 17:PERCENTAGE OF HIV-EXPOSED INFANTS TESTED FOR HIV BY TWO MONTHS,SELECTED REGIONS 2010-2022iEncouragingly,the use of point-of-care EIDwhich has been shown to decrease time to result return and increase linkage to careappears to be increasing.In 2022,905,000 POC cartridges were sold in LM

190、ICs between Abbott and Cepheid,almost a 50 percent increase compared to 2021.iii Further enabling the expansion of POC EID,Cepheids HIV-1 Qual XC cartridge is expected to receive WHO PQ by the end of 2023.This new cartridge simplifies testing processes by removing the need for a thermomixer by utili

191、zing dried blood spots(DBS)directly and negates the need for high-heat incineration for waste disposal.Global interest in combination tests is increasing alongside rollout of the dual HIV/syphilis testCombination tests offer the potential for simultaneous identification of multiple diseases.For exam

192、ple,a systematic review of 175 studies from 56 countries looked at the prevalence of blood-based diseases across over 14 million individuals.The review found that with multi-disease screening,for every one individual diagnosed with HIV,an additional five would be diagnosed with hepatitis B virus(HBV

193、)and three with hepatitis C virus(HCV).There appear to be even greater potential gains for some key populations,with the review estimating that among people who use drugs,over 60 percent would test positive for HIV,HBV,or HIV and almost 20 percent would test positive for multiple infections.xcii The

194、re is also increasing evidence that combination tests are acceptable and feasible for end users.A study in Thailand found that 99.8 percent of clients using a HIV/HBV/HCV combination self-test were satisfied with the process and that it simplified and streamlined service delivery.xciii With multiple

195、 triple combination tests in development and the PQ pipeline,validation and operational research in country contexts would generate important evidence around feasibility and value of integrated screening.xciv Another key combination test for PLHIV is the dual HIV/syphilis test,which is currently ava

196、ilable from three suppliers with WHO PQ.One of these tests is available from SD Biosensor at a cost of US$0.95(EXW)per test as a result of a CHAI/MedAccess ceiling price agreement.xcv,xcviAdoption of the dual test is ongoing with at least 40 countries including it in national policy for either pregn

197、ant women or key populations.xcviii In tandem with increasing access to testing,treatment for syphilis is also critical to avoid preventable deaths,particularly among exposed infants.However,global shortages of benzathine G penicillin,an injectable,long-acting form of penicillin used to treat syphil

198、is,have impacted access.xcix Global action to address supply chain constraints for this product is needed to ensure that syphilis identification is paired with treatment.There are overlapping transmission routes and risk factors between HIV,HBV,and syphilis and comorbidity can lead to higher vertica

199、l transmission risk.This underscores the critical need for integration of tools and service delivery across disease areas to improve health outcomes and save lives,advancing the global goal toward triple elimination.Suppliers continue to develop additional combination tests with growing interest in

200、combination lateral flow products for triple elimination of HIV,HBV,and syphilis,and others.Increased access to combination tests could help increase identifications across diseases and catalyze cost-effective opportunities to integrate service delivery across disease areas by simplifying procuremen

201、t and supply chain processes and improving screening rates across multiple disease areas.Given ANC systems already serve the majority of pregnant women and include routine HIV screening,there is a huge,unaddressed opportunity to close the testing gap during ANC between HIV,HBV,and syphilis and reduc

202、e significant regional disparities in testing coverage.Efforts are needed to strengthen integrated health worker in-service training,strengthen and coordinate timely cross-disease monitoring mechanisms,and engage community members to raise awareness and generate demand.There is an opportunity to bui

203、ld on proven HIV differentiated service delivery models while innovating in community settings to expand access and uptake of comprehensive care.020%40%60%80%100%2010PERCENT9.52012201420162018202020228.9East and Southern Africa 8.18.99.39.49.69.79.8West and Central Africa Global2023 HIV MARKET REPOR

204、T21As discussed in the Testing section,an increasing number of those presenting to treatment are re-engaging with care after an interruption.A South African study from 2017 and 2018 found that 51 percent of people who tested positive for HIV had been previously diagnosed,and 81 percent of these indi

205、viduals had been previously initiated on ART.ci This is concerning given another South African study found that a longer gap between diagnosis and treatment initiation reduced the chance of viral suppression and increased risk of death.cii Over the past four years,CHAIs efforts to tackle supply and

206、demand barriers in the adult AHD market and introduce the WHO-recommended AHD Package of Care across ten focal countries have significantly improved AHD diagnostic and treatment availability for those who need it most.As part of these efforts,CHAI and partners developed a Global AHD Toolkit that inc

207、ludes community materials,programmatic tools,job aids,and training materials.The toolkit has been used by multiple countries,including many outside of the CHAI project,and includes an AHD Commodity Calculator,which supports the quantification of AHD commodities in countries adopting the AHD Package

208、of Care.While great progress has been made thus far,urgent action and innovation is required to reach the goal of fewer than 240,000 AIDS-related deaths by 2030.Programs and partners must aim to reduce the number of people presenting to care with AHD,identify AHD sooner,and link them to appropriate

209、prevention and treatment for OIs.TREATMENTAdvAnced HIv dIseAse Progress toward reducing AIDS-related deaths off track from targets,with care interruptions an ongoing challengeIn 2022 there were still 630,000 AIDS-related deaths globally,an unacceptably high number given widely accessible and low-cos

210、t treatment and testing.i Progress is significantly off track and will likely not meet the 2025 and 2030 Fast-Track targets for reductions in AIDS-related deaths Figure 18.x FIGURE 18:PROGRESS REQUIRED TO REACH GLOBAL REDUCTIONS IN AIDS-RELATED DEATHS TARGETSiThe frequency of clients presenting with

211、 AHD at treatment initiation remains high with recent data suggesting that 30 to 40 percent of people starting ART in LMICs have AHD.c Expanded access to DTG-based regimens,now taken by over 90 percent of adults and hundreds of thousands of children in GA LMICs,has significantly improved treatment o

212、utcomes for PLHIV.Treatment optimization continues as introduction of the best-in-class protease inhibitor,DRV/r,begins to scale up and with the US FDAs approval of long-acting lenacapavir,although a lack of voluntary licensing for the latter threatens access in LMICs.Despite these advancements,trea

213、tment coverage and viral suppression rates,particularly among children and key populations,fall short of the UNAIDS epidemic control targets,resulting in high rates of mortality and morbidity.The global community must continue to ensure HIV treatment services are person-centered,that they are struct

214、ured to support client retention in care and keep them virally suppressed,and that they provide timely screening and treatment for AHD and related OIs to reduce preventable AIDS-related mortality.0300K600K900K1.2M1.5M2010NUMBER OF AIDS-RELATED DEATHS9.520152020202520308.99.39.49.69.79.82030 Target24

215、0,0002025 Target250,000Annual Number of AIDS-Related Deaths2019-20224%Annual Reduction2022-202527%Annual Reduction NeededCLINTON HEALTH ACCESS INITIATIVE22Ensuring access to CD4 testing remains critical as supplier shifts impact market dynamics CD4 testing remains the most critical part of the pathw

216、ay to accessing the AHD package of care.Without the use of CD4 tests to identify AHD,it is estimated up to 50 percent of AHD cases would be missed as half of patients present as asymptomatic and would not be identified via symptom screening.ciii However,the CD4 market is experiencing several signifi

217、cant supplier shifts estimated to impact access to CD4 testing.In May 2022,Abbott announced that it discontinued manufacturing their PIMA CD4 analyzer,but will continue to supply PIMA cartridges,refurbish existing devices,and honor all existing service and maintenance agreements.civSimilarly,BD anno

218、unced in Dec.2022 that they will discontinue production of both the FACSPresto and FACSCount cartridges and devices by the end of 2024,at which time programs must divert any testing currently being done on these devices to other solutions.cv Given the importance of CD4 testing,partners urged supplie

219、rs to reconsider production of CD4 tests or to support technology transfer for local production.While Abbott is open to a technology transfer,a redesign of the analyzer is required as some raw materials are no longer being produced,thus requiring a significant investment from any manufacturer who wo

220、uld be interested in producing the analyzer.cvi Amidst these discussions,there have been some commitments from suppliers of lab-based tests,as well as AccuBio which produces VISITECT,to stay in the market which will help to ensure future access to testing.Countries should begin to plan for these cha

221、nges in the CD4 market while ensuring access to testing for those who need it.To better inform market visibility,CHAI developed a CD4 forecast split by platform Figure 19.CHAI estimates that conventional testing accounts for over 50 percent of total volumes.cvii While South Africa comprises around o

222、ne third of the conventional volumes,this still indicates considerable conventional testing volumes across the rest of LMICs.This forecast is based on historical demand,and future splits across devices may change significantly as these market shifts bear out.Looking forward,CHAI expects increased ut

223、ilization of VISITECT tests to fill the gaps in POC CD4 testing access.Given the evolving CD4 market dynamics,limited national and donor budgets for CD4,and persistent high rates of AHD at presentation,demand generation and CD4 network optimization will be needed.Demand generation will help address

224、barriers to access,improve future planning,and facilitate earlier testing and linkage to treatment,ultimately improving access to the AHD package of care and reducing preventable AIDS-related deaths.Similarly,CD4 network optimization will enable a better understanding of gaps and highlight solutions

225、 that can optimize CD4 coverage for eligible PLHIV using the existing infrastructure.New point-of-care tests for cryptococcal meningitis could simplify linkage to careCryptococcal meningitis(CM)is a common opportunistic infection associated with AHD,and the second leading cause of death among PLHIV.

226、cviii However,currently it is estimated that only a quarter of people in Africa have routine access to cryptococcal antigen(CrAg)testing.cix Expanding access to this critical screening tool is a key step in avoiding preventable AIDS-related deaths.2M4M6M8M10MEST CD4 TESTS RUN IN LMICs202120222023202

227、4202520262027FACSPrestoPimaUnknown PlatformConventionalVISITECT6.0M817K1.7M231K8.7M5.8M806K1.5M469K8.6M5.6M720K1.3M717K8.3M5.4M678K1.3M799K8.1M5.1M1.2M907K639K7.8M4.8M1.1M1.0M598K7.5M4.5M1.0MK1.1M565K7.2MActualsForecast FIGURE 19:LMIC CD4 DEMAND FORECAST SPLIT BY PLATFORMcvii 2023 HIV MARKET REPORT2

228、3Miravista developed the first CE marked urine-based histoplasmosis lateral flow assay(LFA)test,although it is not currently US FDA-approved and is cost prohibitive for many programs.cxi IMMY is in the process of developing a LFA test that is expected to enter the market in 2024.lxxxviii As LFA prod

229、ucts become available at lower prices and significantly reduce complexity compared to existing,lab-based testing options,programs will be able to rapidly expand access.2025 targets for reductions in TB-related deaths among PLHIV are within reach,bolstered by improvements in TB treatment and supplier

230、 capacityWhile there have been significant improvements in access to TB care,an estimated 190,000 PLHIV died of TB globally in 2021.However,with concerted efforts,the 2025 target of 150,000 deaths is well within reach Figure 21.x Achieving this goal will require continued optimization throughout the

231、 cascade of care,including access to optimal TB prevention and treatment regimens.Further enabling future scale-up,a semi-quantitative lateral flow CrAg assay from IMMY is under development and expected to be available in 2023/2024.This test has the potential to simplify linkage to CM treatment by n

232、egating the need for a confirmatory lumbar puncture in a subset of patients.lxxxviii However,further research is still needed to inform WHO guidance.Once CM is identified,access to WHO-recommended treatment is critical to save lives.This includes liposomal amphotericin B(L-AmB)and flucytosine(5FC),k

233、ey components of the induction phase of CM treatment.Between 2021 and 2022,5FC order volumes increased 75 percent and L-AmB order volumes increased 51 percent,as seen by the ARV Procurement Working Group(APWG)and driven by the Unitaid-CHAI Optimal project.As of publication,18 LMICs placed orders for

234、 5FC and 30 placed orders for L-AmB Figure 20.cx Decentralization and price reductions could address critical barriers to histoplasmosis screening Histoplasmosis is a dangerous opportunistic infection acquired by inhaling spores of a fungus typically found in bird and bat droppings.However,an estima

235、ted three quarters of people living in Africa have no access to histoplasmosis diagnostics,and when testing is available its often only accessible at large central facilities.As a result,histoplasmosis is often misdiagnosed as TB and incorrectly treated,leading to preventable deaths.cix Point-of-car

236、e histoplasmosis tests using urine are a promising option to improve access,but pricing and access barriers have limited their use to date.L-AmB Orders PlacedNot pictured:Armenia,Mexico,Nepal5FC Orders PlacedNot pictured:IndiaL-AmB and 5FC Orders PlacedNot pictured:Georgia,Haiti,Sao Tome&PrincipeCHA

237、I,with support from Unitaid,helped tointroduce L-AmB and 5FC at19 hospitals in Uganda,saw a reduction in mortality,reduced side effects,and shortened hospital stays.View MoreFIGURE 20:5FC AND L-AMB ADOPTION MAP,APWGcx View MoreWith support from Unitaid,CHAI partnered with the Medical Mycology Societ

238、y of Nigeria to identify the true burden of histoplasmosis by screening 1,000 AHD patients across 10 sites in Nigeria.This ongoing prevalence study will inform national policy guidelines on histoplasmosis screening for PLHIV with AHD.CLINTON HEALTH ACCESS INITIATIVE24FIGURE 21:NUMBER OF TB-RELATED D

239、EATHS AMONG PLHIV GLOBALLYiOne of the first critical steps in reducing deaths is identifying those at risk of TB and increasing access to TB preventive therapy(TPT).A new modeling study estimates that failure to implement contact tracing and tuberculosis prevention in 29 high-incidence countries cou

240、ld result in almost 850,000 preventable deaths from TB through 2035.The study also found that scaling up TPT prevented deaths from TB and was likely to be cost-effective among PLHIV in 29 high-HIV-incidence countries.cxii The supply of 3HP,an optimal TPT regimen comprising isoniazid(INH)and rifapent

241、ine(RPT),has stabilized following the easing of several years of supply challenges.cxiii As of 2022,3HP has been adopted by 25 countries,an increase of 39 percent compared to 2021.cx For PLHIV specifically,viral suppression is essential to preventing TB-related deaths.However,only 46 percent of PLHI

242、V who developed TB in 2021 were receiving ART,highlighting another critical gap.x There have also been several advances in TB research that could simplify or shorten treatment timelines.New WHO guidance on multi-drug resistant(MDR)TB now recommends the use of a novel all-oral six-month regimen compo

243、sed of bedaquiline,pretomanid,linezolid,and moxifloxacin(BPaLM).cxiv For drug-susceptible TB,treatment usually consists of a six-month rifampicin(RIF)-based regimen.However,new research indicates that an eight-week regimen composed of bedaquiline and linezolid is safe,efficacious,and noninferior to

244、standard treatment.cxv These shorter regimens could help increase treatment adherence and improve treatment outcomes.Mpox downgraded from a public health emergency,but remains a concern for PLHIV,especially those with unsuppressed viral loadsIn May 2023,the global mpox outbreak was downgraded from a

245、 public health emergency of international concern by the WHO.cxvi However,according to a recent cohort study,PLHIV remain at increased risk of mpox infection and accounted for up to half the cases in 2022.The study also found that mortality from mpox among PLHIV increases as CD4 count decreases,sugg

246、esting particular susceptibility for people with AHD.cxvii The WHO continues to recommend PLHIV with AHD as a priority group for mpox vaccination.cxviii Continued disparities in morbidity and mortality among CLHIV demonstrate the need for additional investments in pediatric AHD careChildren living w

247、ith HIV continue to be disproportionately affected by AHD.In 2022,CLHIV accounted for 13 percent of AIDS-related deaths,despite comprising only four percent of PLHIV.x The youngest CLHIV are particularly at risk,with PEPFAR program data showing that CLHIV on ART under five have an increased likeliho

248、od of death compared to older age groups.cxix To better address the needs of CLHIV,it is critical to understand key gaps and challenges in identifying and managing AHD for this group and improve monitoring of drivers and outcomes.A recent article co-authored by CHAI provides an overview of common cl

249、inical presentations of AHD in children and adolescents,and articulates that the prevalence and presentation of opportunistic infections vary significantly between adults and children living with HIV.xi It also highlights the pressing need for additional investments in research and evidence generati

250、on to support the AHD package of care for CLHIV.xi Continued prioritization and increased funding is needed to close the pediatric AHD gap and avoid preventable deaths among CLHIV.Further real-world evidence generation and research alongside concrete actions to address these inequalities remain crit

251、ical moving forward.0100K200K300K400K500K600K700K800K2000NUMBER OF TB-RELATED DEATHS9.5200520102015202020258.98.18.99.39.49.69.79.82025 Target2023 HIV MARKET REPORT25the general population.Stigma and discrimination(including violence and harassment),punitive laws and policies,sparse key population-s

252、pecific HIV data,and poor funding for key population programs contribute to the gaps in ART initiation and retention in care.In at least one-third of reporting countries,concerns about stigma,confidentiality,or other issues resulted in over 10 percent of key populations avoiding the use of healthcar

253、e services,as documented by UNAIDS.x To bridge these disparities,UNAIDS recommends that countries should implement inclusive HIV programs that prioritize the involvement of key populations,repeal discriminatory laws and policies,enhance healthcare provider accountability,and strengthen community eng

254、agement.x Beyond key populations,men continue to be less likely to be on ART than women in sub-Saharan Africa,the Caribbean,and Eastern Europe and Central Asia,likely a result of harmful gender norms and structural barriers.x,cxx UNAIDS has published a framework outlining strategies to address these

255、 challenges,including targeted awareness campaigns and partnerships with community leaders,and support networks to dispel gender-related myths and stereotypes that hinder men from seeking and adhering to treatment.cxx Over 90 percent of adult PLHIV on ART in GA LMICs now take DTG-based regimens CHAI

256、 estimates that DTG use among adults in GA LMICs has reached 91 percent,a ten-percentage point increase from 2021,with an estimated 22.2 million adults on DTG-based regimens in 2022 Figure 23.iii ADULTS ON ARTADULT ART COVERAGE05M10M15M20M25M30MNumber on ART202720262025202420232022202120202019201820

257、1760%64%69%72%76%80%80%60%40%20%0%Coverage(actual/projected)Adult treAtmentNearly 29 million adults on treatment globally in 2022,representing a diverse group of PLHIV with unique needs In 2022,an additional 1.7 million adults(1.5 million in GA LMICs)were on treatment globally compared to 2021,for a

258、 total of nearly 29 million on ART.i,iii Adult treatment coverage in GA LMICs is now 80 percent in 2022,a four-percentage point increase from 2021 Figure 22.i FIGURE 22:ADULTS ON ART AND COVERAGE IN GA LMICsiHowever,despite the increasing number of PLHIV on treatment,some geographies and populations

259、 still face barriers to accessing care.Adult treatment coverage rates in the Middle East and North Africa,Eastern Europe and Central Asia,and Asia and the Pacific are lower than those of other regions.i Furthermore,key population groups in many countries have lower treatment coverage rates compared

260、to 5M10M15M20M25M30M20272026202520242023202220212020(NVP 1%2021-2027)NVPPIs64%21%8%2%21.5M5%81%11%3%23M4%91%4%1%3%93%3%1%25M3%93%3%1%25.6M3%93%3%1%26.2M3%93%3%1%26.7M3%93%3%1%27.2M3%Actual|ProjectedEFV400EFV600DTGADULTS ON ART24.4MFIGURE 23:ADULT INSTI/NNRTI/PI USE IN GA LMICscxxi CLINTON HEALTH ACC

261、ESS INITIATIVE26benefits such as fewer side effects,lower pill burden,reduced risk of drug-drug interactions,and lower costs.These findings supplement evidence from the NADIA,VISEND,and ARTIST studies supporting the use of DTG plus recycled TDF/3TC for people failing a NNRTI-based regimen.cxxv,cxxvi

262、,cxxvii While WHO guidelines have not been updated to reflect this,the WHO has committed to re-evaluating TDF recycling and other“second-line”recommendations.Adoption of TDF recycling could have major implications on NRTI use in GA LMICs.CHAI estimates that zidovudine(AZT)use will be significantly r

263、educed with widespread adoption of TDF recycling Figure 25.Consequently,ensuring the availability of low-volume products,including AZT for use in cases of TDF intolerance,will be critical for equitable and uninterrupted access to treatment.FIGURE 25:POTENTIAL IMPACT OF TDF RECYCLING ON ADULT NRTI BA

264、CKBONE USE IN 2027iiiRecent studies reevaluate current recommendations on DTG and rifampicin dosing during TB coinfection and address weight-gain concernsDTG has proven to be safe and effective when used during rifampicin-based TB treatment,and the WHO currently recommends doubling the dose of DTG f

265、or TB coinfected clients for the duration of RIF-based treatments.cxxviii,lv Recent research,however,suggests that this may be unnecessary.RADIANT-TB,a non-comparative randomized controlled trial,found similar virological outcomes in once-daily DTG versus the recommended twice-daily dosing for clien

266、ts on rifampicin-based TB treatment.cxxix While further research is required in this area,these findings could potentially improve ART adherence,minimize unnecessary ARV exposure,and reduce program costs.Given the widespread use of DTG across first-and second-line treatment,and the data challenges p

267、rograms face in differentiating between DTG used in various lines of therapy,CHAIs estimates are aggregated across lines of treatment.The global community may need to revisit the traditional treatment classification structure utilizing lines of therapy and consider categorizing clients based on prio

268、r drug exposure instead.cxxii New research continues to show that recycling tenofovir disoproxil fumarate(TDF)-based nucleoside reverse transcriptase inhibitor(NRTI)backbones is effective when used with DTG,which could have implications on treatment sequencing and DTG use.Results from D2EFT,a random

269、ized open-label study,showed that a switch to TDF+XTC+DTG without universal access to genotyping was non-inferior to using DRV/r and two NRTIs following treatment failure on a non-nucleoside reverse transcriptase inhibitor(NNRTI).cxxiii The study also found a second-line regimen comprised of just DT

270、G and DRV/r to be superior to DRV/r and two NRTIs Figure 24,although more research is needed on two-drug regimens in LMICs,especially those that do not contain TDF which is used to cross-treat hepatitis B.FIGURE 24:D2EFT STUDY RESULTScxxiiiSimilarly,in the Second-Line Switch to DTG(2SD)prospective t

271、rial in Kenya,researchers found that switching virally suppressed clients on second-line treatment from a ritonavir-boosted protease inhibitor(PI)-based regimen to a DTG-based regimen(without genotypic resistance information)was non-inferior to a continuation of the PI-based regimen.cxxiv A transiti

272、on from PI-based regimens to DTG-based regimens offers ARM 3(where XTC=3TC or FTC)Non-inferior to the standard of careTDF+XTC+DTGARM 2Superior to the standard of careDRV/r+DTGARM 1Standard of careDRV/r+2 NRTIsGreaterCD4 gainscomparedto thestandard of care0250K500K750K1M1.25MStatus Quo:2L TDF Recycli

273、ng Not RecommendedWHO Guidelines Recommend TDF Recycling in 2LEST PEOPLE ON AZT(2027)80-290K970K2023 HIV MARKET REPORT27A recent study involving a secondary analysis of NAMSAL and ADVANCE trial data,both of which reported increased weight gain with DTG use compared to efavirenz(EFV),found that hyper

274、tension associated with ART can be effectively treated with low-cost generic anti-hypertensive drugs.cxxx,cxxxi,cxxxii The findings suggest that weight gain,rather than specific ARVs,accounted for the observed blood pressure differences.Notably,the study also found that the weight gain initially asc

275、ribed to DTG use in the ADVANCE trial was instead a result of the absence of weight-gain suppression due to EFV-induced nausea and other side effects,which did not occur with DTG use.cxxxii,cxxxiiiSlow initial uptake of DRV/r(400/50 mg)gains momentum with PEPFAR procurement and potential WHO guideli

276、ne revisionsHistorically,the adult second-line market in GA LMICs has been dominated by the protease inhibitors atazanavir/ritonavir(ATV/r)and lopinavir/ritonavir(LPV/r).From 2012 to 2022,ATV/rs market share within the PI category increased from six to 59 percent due to its lower cost,better clinica

277、l profile,and significantly lower pill burden compared to LPV/r.lxxxviii A third PI,darunavir(DRV),is considered the best-in-class protease inhibitor due to its high genetic barrier to resistance,improved viral suppression rates,better tolerability,and lower pill burden compared to LPV/r.However,no

278、affordable generic product co-formulated with ritonavir was available in LMICs until Hetero Labs DRV/r(400/50 mg)product received WHO PQ in July 2021 and was launched at US$17.50/pack thanks to a CHAI-Unitaid pricing agreement.cxxxiv Despite this availability,and pricing below that of LPV/r,uptake i

279、n GA LMICs has been slow to date.A major challenge limiting DRV/r uptake at scale is its status in the WHO guidelines as an alternative second-line option following treatment failure with DTG.PEPFAR had also been unable to procure Heteros DRV/r product given that it is WHO prequalified and not US FD

280、A-approved,thus limiting access to DRV/r in PEPFAR-supported countries.However,these barriers are beginning to fall.PEPFAR can now procure Heteros product and has initiated orders.CHAI expects this will result in increased adoption beyond the 12 LMICs currently procuring DRV/r Figure 26.cxxxv Additi

281、onally,PEPFAR has signaled that it will no longer procure LPV/r(200/50 mg)tablets as it looks to scale optimal DRV/r in line with recent COP guidance.However,it is important to note that some use cases remain for LPV/r,such as in the treatment of TB/HIV co-infected clients who need a PI,as DRV/r and

282、 ATV/r cannot be used alongside rifampicin-based TB treatment.FIGURE 26:DRV/r(400/50 MG)ADOPTION MAP,APWG,AS OF Q3 2023cxxxvIn addition to PEPFARs ability to procure,the WHO has committed to reviewing its second-line treatment guidelines,including DRV/rs positioning and NRTI recycling,following stro

283、ng community advocacy.In Dec.2021,Afrocab issued a community position statement calling for an update to the WHO guidelines to promote DRV/r to the preferred PI for second-line use.cxxxvi Following this,in Mar.2023,Afrocab issued a follow-on letter demanding WHO leadership on the issue and continuin

284、g to call for a guideline update.cxxxvii Not Pictured:Comoros,Cape Verde,Nicaragua,Sri Lanka CHAI/Unitaid-supported rolloutDRV/r(400/50 mg)Orders Placed or Delivered“We call on the WHO to urgently remedy the current status of DRV/r and replace LPV/r as the preferred regimen with immediate effect The

285、re is no justifiable reason to maintain the current second-line regimen now that a fixed-dose combination of DRV/r is available at an affordable price.”Kenly SikweseAfrocab TreatmentAccess PartnershipcxxxviiCLINTON HEALTH ACCESS INITIATIVE28FIGURE 28:ARV APPROVAL HISTORYcxliin clinical outcomes.cxxx

286、viii Advances in antiretroviral therapy,including combination therapies,NNRTIs,PIs,and INSTIs,led to the WHOs endorsement of TDF/3TC/DTG(TLD)as the preferred first-line regimen in 2018 Figure 28.cxxxix,cxl TLD offers rapid viral suppression,a high genetic barrier to resistance,fewer side effects,and

287、 a lower price compared to TDF/3TC/EFV(TLE),enhancing treatment outcomes.Currently available optimal ARVs are effective,well tolerated,and safe.However,given all available options in LMICs consist of daily oral pills,there are still challenges associated with daily(and lifelong)adherence.Long-acting

288、 options,including those in the development pipeline,hold the potential to improve adherence and discretion Figure 29.Dual therapy with novel agents has re-emerged as a potential option both for long-acting non-oral combinations and more traditional shorter acting oral regimens.Dual therapy in LMICs

289、 will have to account for cross-treatment of hepatitis B,which cannot be achieved without the presence of tenofovir in two-drug treatment regimens.One such long-acting product with the potential to positively impact HIV treatment is injectable lenacapavir(LEN)the first capsid inhibitor.In Dec.2022,G

290、ilead received regulatory approval from the US FDA for LEN,based on results from the CAPELLA trial,for six-month subcutaneous injections alongside other ARVs in treatment-experienced adults with multidrug-resistant HIV.lxii,cxlii However,the absence of generic licensing at the time of publication po

291、ses a major challenge to access in LMICs.The phase 2 CALIBRATE trial provided evidence on the efficacy of LEN in treatment-nave PLHIV.Results demonstrated that subcutaneous LEN in combination with other oral ARVs maintained high rates of virologic suppression through week 80 in the study population.

292、cxliii20%40%60%80%100%2022PI MARKET SHARE20232024202520262027100%Other PIsModerate DRVr UptakeAggressive DRV/r Uptake8.19.3889.71%7-9%12-18%18-30%24-41%Zidovudine19851990199520002005201020152020Pre-HAART Era(Mono/Dual Therapy)*HAART Era(TripleTherapy)*POTENCYTOXICITYPOTENCYTOXICITYAZT(1987)2 Tablets

293、 3x DailyDidanosineStavudineLamivudineSaquinavirRitonavirNevirapineEfavirenzAbacavirLopinavir/RitonavirTenofovir Disoproxil FumarateAtazanavirEmtricitabineDarunavirRaltegravirEtravirineElvitegravirDolutegravirTenofovir AlafenamideDoravirineBictegravirFostemsavirAZT/3TC+LPV/r(2001)3 Tablets 2x DailyT

294、DF/3TC/EFV(2006)1 Tablet 1x DailyTDF/3TC/DTG(2017)1 Tablet 1x DailyPOTENCYTOXICITY*Adapted from WHO;approval dates based on US FDA approval;ARVs listed are not exhaustiveBased on these market shifts,CHAI has modeled the following scenarios for DRV/r uptake in the coming years Figure 27.The first sce

295、nario portrays the current state with PEPFARs decision to procure DRV/r and discontinue LPV/r(200/50 mg)procurement.The second scenario envisions a situation where the WHO updates its guidelines by early 2024,promoting DRV/r to the status of preferred second-line treatment option.FIGURE 27:DRV/r(400

296、/50 MG)FORECAST(EXCLUDING SOUTH AFRICA)iii Development of treatment pipeline products continues,and US FDA approval of lenacapavir adds another long-acting product to the mix,but further optimization is needed Decades ago,AZT monotherapy(the first ARV for HIV)showed positive impacts on outcomes for

297、PLHIV but was not sufficient for sustained improvements 2023 HIV MARKET REPORT29FIGURE 29:ARV PIPELINE PRODUCTS AND TRIALSlxxxviHowever,it is not known when Gilead will file an application for an updated label to include LENs use in treatment-nave PLHIV,or when the US FDA will approve it.Despite LEN

298、s benefits,it requires coadministration with an optimized backbone regimen,all of which currently available are daily oral pills.To reap the full benefits of long-acting treatment in terms of reduced clinic visits and improved adherence,development of novel long-acting ARVs to be paired with LEN,or

299、studies evaluating novel combinations of existing long-acting products such as CAB and LEN,are necessary.In Feb.2023,Gilead announced results from a phase 1b trial that assessed the safety and efficacy of LEN in combination with the broadly neutralizing antibodies,teropavimab(TAB)and zinlirvimab(ZAB

300、),as a potential long-acting treatment.cxliv The combination was well tolerated and highly efficacious.Phase 2 of the study commenced in May 2023.cxlv While this development appears promising,stakeholders need to address potential issues,such as the high cost of bNAbs,the need for appropriate select

301、ion and ongoing monitoring,and the required health infrastructure for storage and distribution,to ensure equitable access in LMICs.A phase 2 study sponsored by Gilead and in collaboration with Merck is underway to assess the efficacy of oral weekly islatravir(ISL)in combination with bi-annual subcut

302、aneous LEN in virologically suppressed PLHIV.cxlvi Notably,ISL remains a weekly oral pill,reinforcing the need for development of longer-acting non-oral formulations to be administered with LEN.CHAI assessment shows that key stakeholders have a strong interest in adoption of long-acting HIV treatmen

303、t,but introduction likely to be complexCHAI,funded by Unitaid and in partnership with ministries of health(MOHs),conducted a landscape assessment in Kenya,Nigeria,and South Africa to evaluate country readiness and outline next steps for the introduction of long-acting ART.iii The assessment involved

304、 data collection and consultations with MOH personnel/key opinion leaders,community activists,and discussions with healthcare workers.In all three countries,stakeholders expressed their excitement at the transformational potential of long-acting products,but recognized that health systems will requi

305、re key changes to facilitate broad access to long-acting products.Across countries,stakeholders held varying opinions on the use of innovator products,selecting initial sub-populations for prioritization,seeking local evidence,and anticipated implementation of client choice.Key similarities are summ

306、arized in Figure 30.FIGURE 30:LONG-ACTING HIV TREATMENT LANDSCAPE ASSESSMENT FINDINGSiii Supply security a priority,with availability of multiple generics preferred Countries will leverage learnings from sexual and reproductive health programs to harmonize client choice and supply quantificationPROC

307、UREMENT&SUPPLY Strong pharmacovigilance process needed Review and update of existing client monitoring processes for long-acting ART integration requiredMONITORING&UPTAKE Funding gaps for trainings are common,however,many HCWs are already trained to administer injections DSD may be limited by polici

308、es on where injections can be given(facility vs non-facility)Interest in private sector engagement(South Africa and Kenya)SERVICE DELIVERY Strong interest in adoption No expected changes in registration pathwaysADOPTION®ISTRATIONCABOTEGRAVIR*Not exhaustive,further combinations in Phase 1 trials*D

309、aily oral combinations,not long-acting ARVsISLATRAVIRLENACAPAVIRLEN+TAB/ZAB(bNAbs)6 Month InjectionLEN+BIC*Daily OralISL+LENWeekly OralISL+DOR*Daily OralPHASE 2APPROVEDLEN(6 Month SC Injection)+Optimized Background Regimen(Daily Oral)CAB+RPV2 Month IM InjectionPHASE 3CLINTON HEALTH ACCESS INITIATIVE

310、30suppression among CLHIV was 46 percent in 2022 compared to 67 percent and 76 percent in adult males and females respectively.x The number of AIDS-related deaths in children was 84,000 in 2022,accounting for approximately 13 percent of all AIDS-related deaths despite children making up only four pe

311、rcent of all PLHIV.i This is concerning,especially considering that optimal low-cost treatment is now available,and underscores the need to intensify pediatric case-finding and break down barriers hindering access to sustained,high quality care.To reverse this current trend,urgent and coordinated ef

312、forts from national and international stakeholders are required to address the unique challenges faced by pediatric populations.Continued adoption and scale-up of pediatric DTG has improved adherence and viral suppression rates two years post rollout The widespread availability and affordability of

313、generic pediatric formulations of DTG marks a significant achievement in the pediatric HIV response.viii At the time of publication,more than 80 LMICs have commenced procurement of pediatric DTG,with 160,000 children accessing the product Figure 33.Beyond just adoption,data from PEPFAR-supported cou

314、ntries show improved viral suppression rates in children below 15 years old following rollout of pediatric DTG.cxlvii CHAI estimates that,in 2022,62 percent of children on pediatric treatment backbones were on DTG-based regimens based on data from 17 LMICs representing 64 percent of CLHIV on ART glo

315、bally Figure32.FIGURE 32:ESTIMATED PEDIATRIC THIRD-POSITION DRUG USE IN GA LMICsiiipedIAtrIc treAtmentThe number of children on ART globally continues to fall,reinforcing the need for renewed focus on this underserved population In 2022,only 880,000 of the 1.5 million children living with HIV were o

316、n lifesaving ART,continuing a three-year downward trend in treatment coverage.Although some decline is expected as children age into adulthood,pediatric treatment coverage remains concerningly low with over 600,000 CLHIV not accessing care due to gaps in pediatric case-finding,linkage to treatment,a

317、nd retention in care.In 2022,global pediatric ART coverage increased only marginally to 57 percent,significantly lower than adult coverage at 77 percent,and posing a large inequity for this vulnerable group.i Similarly,in GA LMICs,pediatric ART coverage is 54 percent,compared to an adult coverage ra

318、te of 80 percent.i,iii If the current stagnant and downward trends in both case-finding and retention continue,CHAI estimates that pediatric ART coverage in GA LMICs will only reach 69 percent in 2027.However,achieving a five percent year-over-year(YoY)increase in the number of CLHIV on ART could dr

319、astically increase pediatric coverage to close to 100 percent by 2027 Figure 31.FIGURE 31:ACTUAL AND FORECASTED CHILDREN ON ART AND PEDIATRIC ART COVERAGE IN GA LMICScxxiThe consequences of poor treatment coverage are evident with 50 percent of children estimated to die by age two without treatment.

320、xc Globally,viral load 2027Status Quo:#on ARTStatus Quo:CoverageCHILDREN ON ARTCOVERAGE200K400K600K800K1.0M1.2M1.4M20%40%60%80%100%5%YoY Increase:#on ART5%YoY Increase:Coverage2021201820192020202520262024202320220.00.20.40.60.81.0202020212022DTGLPV/rEFVNVP24%62%5%24%52%19%3%17%44%36%3%11%2023 HIV MA

321、RKET REPORT31FIGURE 34:TORPEDO STUDY RESULTScxlviiiIn parallel to increased adoption,research continues to indicate a preference for,and improved viral suppression with,DTG use in children.The TORPEDO study(conducted in Benin,Nigeria,and Uganda),which assessed client,caregiver,and healthcare worker

322、treatment preferences,found a strong preference for pDTG compared to previously used regimens.cxlviii Most of the ART-experienced study participants were previously receiving LPV/r tablets(83 percent)or LPV/r pellets(14 percent).Most healthcare workers noted an improvement in adherence due to pDTGs

323、enhanced palatability and ease of administration.Healthcare workers responded to an open-ended question about their experience with prescribing pDTG,and over two-thirds noted improved weight gain and adherence for their clients,aligned with findings from the ODYSSEY and CHAPAS-4 trials.cxlix,cl Addi

324、tionally,after the transition to DTG,the proportion of CLHIV in the study with an undetectable viral load increased by 25 and 18 percentage points in Benin and Nigeria respectively at 6 months.The proportion of CLHIV with undetectable viral load at baseline in Uganda was higher as compared to the ot

325、her countries and did not see the same increase at six months Figure 34.Such real-world evidence from LMIC settings will serve as a catalyst for continued uptake of optimal pDTG-based regimens,further improving adherence and viral suppression,leading to improved treatment outcomes in children.FIGURE

326、 33:PEDIATRIC DTG ADOPTION MAP,APWG,AS OF Q3 2023cxxxvOrders Placed or DeliveredNot pictured:Albania,Belarus,Cape Verde,Comoros,Moldova,Sao Tome&Principe,UkraineProcurement Conversations OngoingNot pictured:BermudaNo DataVL 1,000 copies/mLVL 2001000 copies/mLVL 50200 copies/mLUndetectable(VL3 months

327、 and 6-24.9 kgpDTG 10 mg dispersible,scored tablets expected to still be needed for children 3-5.9 kg and under 3 months,those being treated for TB with rifampicin,and those on second and third-line ARTELIGIBILITY Plan for future single and dual product procurement for special circumstances Develop

328、a transition plan for pALDPROCUREMENT&SUPPLY Review and adapt M&E systems Review pALD uptake and adjust as neededMONITORING Modify clinical materials Conduct trainings Engage PLHIV and caregiversTRAINING&CAPACITY BUILDING Review stock status and pipeline orders Quantify pALD neededFORECASTING&QUANTI

329、FICATION2023 HIV MARKET REPORT33pALD,and future opportunities include the introduction of pediatric DRV/r for use by children failing on DTG and newer,more tolerable NRTI backbone options that include TAF Figure 37.More details on these pipeline products can be found in this section.Pediatric DRV/r

330、120/20 mg(pDRV/r)CHAI,with funding from Unitaid,is working with Laurus Labs to develop generic pDRV/r(120/20 mg)tablets with the goal of filing with the US FDA in the first half of 2024.clvi pDRV/r is a best-in-class protease inhibitor with improved viral suppression rates and improved tolerability

331、compared to LPV/r.pDRV/r has proven efficacy in both treatment-nave and experienced groups,including children previously exposed to protease inhibitors.Given these benefits,pDRV/r,when available,will replace LPV/r and significantly improve the management of CLHIV 3 years old and over 10 kg who fail

332、DTG-based regimens or who are unable to take DTG.CHAIs pDRV/r Product Profile is available on the CHAI HIV New Product Introduction Toolkit(www.newhivdrugs.org/resource-library/tags/pdrv-r).Pediatric TAF(pTAF)CHAI is working as a formulation development partner with support from Unitaid,in collabora

333、tion with Penta Infectious Diseases Network and Gilead,for the a thin flexible strip containing DTG and flavored with mint,is administered via placement on the tongue or inside of the cheek where it sticks and dissolves in saliva.This new technology could have benefits in terms of ease of drug administration but is unlikely to replace pDTG tablets given its expected higher price and higher“pill”bu