HIV prevention for the next decade: Appropriate, person-centred, prioritised, effective, combination prevention.

UNAIDS and a broad range of partners have collaborated to establish a new set of HIV prevention targets to be achieved by 2025 as an intermediate step towards the sustainable development target for 2030.The number of new HIV infections in the world continues to decline, in part due to the extraordinary expansion of effective HIV treatment. However, the decline is geographically heterogeneous, with some regions reporting a rise in incidence. The incidence target that was agreed for 2020 has been missed.A range of exciting new HIV prevention technologies have become available or are in the pipeline but will only have an impact if they are accessible and affordable and delivered within systems that take full account of the social and political context in which most infections occur. Most new infections occur in populations that are marginalised or discriminated against due to structural, legal, and cultural barriers.The new targets imply a new approach to HIV prevention that emphasises appropriate, person-centred, prioritised, effective, combination HIV prevention within a framework that reduces existing barriers to services and acknowledges heterogeneity, autonomy, and choice.These targets have consequences for people working in HIV programmes both for delivery and for monitoring and evaluation, for health planners setting local and national priorities, and for funders both domestic and global. Most importantly, they have consequences for people who are at risk of HIV exposure and infection.Achieving these targets will have a huge impact on the future of the HIV epidemic and put us back on track towards ending AIDS as a public health threat by 2030.

Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030.

BACKGROUND: UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the impact of achieving those targets. METHODS AND FINDINGS: We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19-related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections. CONCLUSIONS: The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023.

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic.

Epidemiological metrics and benchmarks for a transition in the HIV epidemic.

Peter Godfrey-Faussett and colleagues present six epidemiological metrics for tracking progress in reducing the public health threat of HIV.

Towards an improved investment approach for an effective response to HIV/AIDS.

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

Knowing your HIV/AIDS epidemic and tailoring an effective response: how did India do it?

Tremendous global efforts have been made to collect data on the HIV/AIDS epidemic. Yet, significant challenges remain for generating and analysing evidence to allocate resources efficiently and implement an effective AIDS response. India offers important lessons and a model for intelligent and integrated use of data on HIV/AIDS for an evidence-based response. Over the past 15 years, the number of data sources has expanded and the geographical unit of data generation, analysis and use for planning has shifted from the national to the state, district and now subdistrict level. The authors describe and critically analyse the evolution of data sets in India and how they have been utilised to better understand the epidemic, advance policy, and plan and implement an increasingly effective, well-targeted and decentralised national response to HIV and AIDS. The authors argue that India is an example of how 'know your epidemic, know your response' message can effectively be implemented at scale and presents important lessons to help other countries design their evidence generation systems.

Understanding the modes of transmission model of new HIV infection and its use in prevention planning.

The modes of transmission model has been widely used to help decision-makers target measures for preventing human immunodeficiency virus (HIV) infection. The model estimates the number of new HIV infections that will be acquired over the ensuing year by individuals in identified risk groups in a given population using data on the size of the groups, the aggregate risk behaviour in each group, the current prevalence of HIV infection among the sexual or injecting drug partners of individuals in each group, and the probability of HIV transmission associated with different risk behaviours. The strength of the model is its simplicity, which enables data from a variety of sources to be synthesized, resulting in better characterization of HIV epidemics in some settings. However, concerns have been raised about the assumptions underlying the model structure, about limitations in the data available for deriving input parameters and about interpretation and communication of the model results. The aim of this review was to improve the use of the model by reassessing its paradigm, structure and data requirements. We identified key questions to be asked when conducting an analysis and when interpreting the model results and make recommendations for strengthening the model's application in the future.

Achieving the 95 95 95 targets for all: A pathway to ending AIDS.

In December 2020, UNAIDS released a new set of ambitious targets calling for 95% of all people living with HIV to know their HIV status, 95% of all people with diagnosed HIV infection to receive sustained antiretroviral therapy, and 95% of all people receiving antiretroviral therapy to have viral suppression by 2025. Adopted by United Nations Member states in June 2021 as part of the new Political Declaration on HIV and AIDS, these targets, combined with ambitious primary prevention targets and focused attention to supporting enablers, aim to bridge inequalities in treatment coverage and outcomes and accelerate HIV incidence reductions by focusing on progress in all sub-populations, age groups and geographic settings. Here we summarise the evidence and decisions underpinning the new global targets.

Innovations, adaptations, and accelerations in the delivery of HIV services during COVID-19.

During 2020, the COVID-19 pandemic disrupted the delivery of HIV prevention and treatment services globally. To mitigate the negative consequences of the pandemic, service providers and communities adapted and accelerated an array of HIV interventions to meet the needs of people living with HIV and people at risk of acquiring HIV in diverse geographical and epidemiological settings. As a result of these adaptations, services such as HIV treatment showed programmatic resilience and remained relatively stable in 2020 and into the first half of 2021. To review lessons learned and suggest which novel approaches to sustain, UNAIDS convened a virtual consultation on Feb 1-2, 2022, which was attended by a range of stakeholders from different areas of global HIV response.

Global and regional epidemiology of HIV-1 recombinants in 1990-2015: a systematic review and global survey.

BACKGROUND: Global HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identified worldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015. METHODS: We assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched the PubMed, Embase (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) databases for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data were collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses were done for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, CRD42017067164. FINDINGS: Our global data collection yielded an HIV-1 molecular epidemiology database of 383 519 samples from 116 countries in 1990-2015. We found that the proportion of recombinants increased over time, both globally and in most regions, reaching 22·8% (7 978 517 of 34 921 639) of global HIV-1 infections in 2010-15. Both the proportion and the number of distinct CRFs detected increased over time to 16·7% and 57 CRFs in 2010-15. The global and regional distribution of HIV-1 recombinants was diverse and evolved over time, and we found large regional variation in the numbers (0-44 CRFs), types (58 distinct CRFs), and proportions (0-80·5%) of HIV-1 recombinants. Globally, CRF02_AG was the most prevalent recombinant, accounting for 33·9% (2 701 364 of 7 978 517) of all recombinant infections in 2010-15. URFs accounted for 26·7% (2 131 450 of 7 978 517), CRF01_AE for 23·0% (1 838 433), and other CRFs for 16·4% (1 307 270) of all recombinant infections in 2010-15. Although other CRFs accounted for small proportions of infections globally (<1% each), they were prominent in regional epidemics, including in east and southeast Asia, west and central Africa, Middle East and north Africa, and eastern Europe and central Asia. In addition, in 2010-15, central Africa (21·3% [243 041 of 1 143 531]), west Africa (15·5% [838 476 of 5 419 010]), east Africa (12·6% [591 140 of 4 704 986]), and Latin America (9·6% [153 069 of 1 586 605]) had high proportions of URFs. INTERPRETATION: HIV-1 recombinants are increasingly prominent in global and regional HIV epidemics, which has important implications for the development of an HIV vaccine and the design of diagnostic, resistance, and viral load assays. Continued and improved surveillance of the global molecular epidemiology of HIV is crucial. FUNDING: None.

Improved estimates of India's HIV burden in 2006.

BACKGROUND & OBJECTIVE: HIV estimates in India were based on HIV sentinel surveillance (HSS) data and several assumptions. Expansion of sentinel surveillance to all districts and community based HIV prevalence measured by National Family Health Survey-3 (NFHS-3) in 2006 provided opportunity to replace many of the assumptions with evidence based information and improve the HIV estimate closer to reality. This article presents a detailed account of the methodology used for the 2006 HIV burden estimates for India. METHODS: State-wise adult HIV prevalence among different risk groups observed from HSS 2006 was adjusted for site level variations using a random effects model and for the previous four years the same was back calculated using trend equations derived from a mixed effects logistic regression model based on consistent sites prevalence. The adjusted HIV prevalence among the general population was calibrated to the estimates from NFHS-3. Overall point estimates of adult HIV prevalence in each State for 2002-2006 were derived from the UNAIDS Workbook and projected for the period 1985-2010. The results were put into Spectrum to derive estimates of the number of people living with HIV in all ages and other epidemic impacts. RESULTS: National adult HIV prevalence was 0.36 per cent (range 0.29-0.46%) and the estimated number of people living with HIV was 2.47 million (range 2.0-3.1 million) in 2006. The national adult HIV prevalence remains stable around 0.4 per cent between 2002 and 2006. The States with the highest estimated prevalence were Manipur, Nagaland and Andhra Pradesh. The States with the highest burden were Andhra Pradesh, Maharashtra, Karnataka and Tamil Nadu. INTERPRETATION & CONCLUSION: The improvement in the 2006 estimates of the HIV burden in India is attributable to the expanded sentinel surveillance and representative data from the population-based survey in 2006, combined with an improved analysis. Despite the downward revision, India continues to face a formidable challenge to provide prevention, treatment and care to those in need.

Correction: What Is Required to End the AIDS Epidemic as a Public Health Threat by 2030? The Cost and Impact of the Fast-Track Approach.

[This corrects the article DOI: 10.1371/journal.pone.0154893.].

HIV estimates through 2018: data for decision-making.

BACKGROUND: Global targets call for a 75% reduction in new HIV infections and AIDS deaths between 2010 and 2020. UNAIDS supports countries to measure progress towards these targets. In 2019, this effort resulted in revised national, regional and global estimates reflecting the best available data. METHODS: Spectrum software was used to develop estimates for 170 countries. Country teams from 151 countries developed HIV estimates directly and estimates for an additional 19 country were developed by UNAIDS based on available evidence. 107 countries employed models using HIV prevalence data from sentinel surveillance, routinely collected HIV testing and household surveys while the remaining 63 countries applied models using HIV case surveillance and/or reported AIDS deaths. Model parameters were informed by the UNAIDS Reference Group on Estimates, Modeling and Projections. RESULTS: HIV estimates were available for 170 countries representing 99% of the global population. An estimated 37.9 million (uncertainty bounds 32.7-44.0 million) people were living with HIV in 2018. There were 1.7 million (1.4-2.3 million) new infections and 770 000 (570 000-1.1 million) AIDS-related deaths. New HIV infections declined in five of eight regions and AIDS deaths were declining in six of eight regions between 2010 and 2018. CONCLUSION: The estimates demonstrate progress towards ending the AIDS epidemic by 2030, however, through 2018 declines in new HIV infections and AIDS-related deaths were not sufficient to meet global interim targets. The UNAIDS estimates have made important contributions to guide decisions about the HIV response at global, regional and country level.

Global, regional and country-level 90-90-90 estimates for 2018: assessing progress towards the 2020 target.

BACKGROUND: In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and partners set the 90-90-90 target for the year 2020: diagnose 90% of all people living with HIV (PLHIV); treat 90% of people who know their status; and suppress the virus in 90% of people on treatment. In 2015, countries began reporting to UNAIDS on progress against 90-90-90 using standard definitions and methods. METHODS: We used data submitted to UNAIDS from 170 countries to assess country-specific progress towards 90-90-90 through 2018. To assess global and regional progress, overall and by sex for adults aged 15 years and older, we combined country-reported data with estimates generated with a Bayesian hierarchical model. RESULTS: A total of 60 countries reported on all three 90s in 2018, up from 23 in 2015. Among all PLHIV worldwide, 79% (67-92%) knew their HIV status. Of these, 78% (69-82%) were accessing treatment and 86% (72-92%) of people accessing treatment had suppressed viral loads. Of the 37.9 million (32.7-44.0 million) PLHIV worldwide, 53% (43-63%) had suppressed viral loads. The gap to fully achieving 73% of PLHIV with suppressed viral load was 7.7 million; 15 countries had already achieved this target by 2018. CONCLUSION: Increased data availability has led to improved measures of country and global progress towards the 90-90-90 target. Although gains in access to testing and treatment continue, many countries and regions are unlikely to reach the 90-90-90 target by 2020.

Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis.

BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None.

Frontloading HIV financing maximizes the achievable impact of HIV prevention.

INTRODUCTION: Due to the nature of funding, national planners and international donors typically balance budgets over short time periods when designing HIV programmes (˜5-year funding cycles). We aim to explicitly quantify the cost of short-term funding arrangements on the success of future HIV prevention programmes. METHODS: Using mathematical models of HIV transmission in Kenya, we compare the impact of optimized combination prevention strategies under different constraints on investment over time. Each scenario has the same total budget for the 30-year intervention period but the pattern of spending over time is allowed to vary. We look at the impact of programmes with decreasing, increasing or constant spending across 5-year funding cycles for a 30-year period. Interventions are optimized within each funding cycle such that strategies take a short-term view of the epidemic. We compare these with two strategies with no spending pattern constraints: one with static intervention choices and another flexible strategy with interventions changed in year ten. RESULTS AND DISCUSSION: For the same total 30-year budget, greatest impact is achieved if larger initial prevention spending is offset by later treatment savings which leads to accumulating benefits in reduced infections. The impact under funding cycle constraints is determined by the extent to which greater initial spending is permitted. Short-term funding constraints and funds held back to later years may reduce impact by up to 18% relative to the flexible long-term strategy. CONCLUSIONS: Ensuring that funding arrangements are in place to support long-term prevention strategies will make spending most impactful. Greater prevention spending now will bring considerable returns through reductions in new infections, greater population health and reductions in the burden on health services in the future.

Comment on "Using geospatial mapping to design HIV elimination strategies for sub-Saharan Africa".

A recent study showed how geospatial mapping can be used to improve Lesotho's HIV treatment program to achieve the 90-90-90 targets set by the United Nations but incorrectly describes "treatment as prevention" as the UN's strategy for a successful national AIDS response.

HIV prevention where it is needed most: comparison of strategies for the geographical allocation of interventions.

INTRODUCTION: A strategic approach to the application of HIV prevention interventions is a core component of the UNAIDS Fast Track strategy to end the HIV epidemic by 2030. Central to these plans is a focus on high-prevalence geographies, in a bid to target resources to those in greatest need and maximize the reduction in new infections. Whilst this idea of geographical prioritization has the potential to improve efficiency, it is unclear how it should be implemented in practice. There are a range of prevention interventions which can be applied differentially across risk groups and locations, making allocation decisions complex. Here, we use mathematical modelling to compare the impact (infections averted) of a number of different approaches to the implementation of geographical prioritization of prevention interventions, similar to those emerging in policy and practice, across a range of prevention budgets. METHODS: We use geographically specific mathematical models of the epidemic and response in 48 counties and major cities of Kenya to project the impact of the different geographical prioritization approaches. We compare the geographical allocation strategies with a nationally uniform approach under which the same interventions must be applied across all modelled locations. RESULTS: We find that the most extreme geographical prioritization strategy, which focuses resources exclusively to high-prevalence locations, may substantially restrict impact (41% fewer infections averted) compared to a nationally uniform approach, as opportunities for highly effective interventions for high-risk populations in lower-prevalence areas are missed. Other geographical allocation approaches, which intensify efforts in higher-prevalence areas whilst maintaining a minimum package of cost-effective interventions everywhere, consistently improve impact at all budget levels. Such strategies balance the need for greater investment in locations with the largest epidemics whilst ensuring higher-risk groups in lower-priority locations are provided with cost-effective interventions. CONCLUSIONS: Our findings serve as a warning to not be too selective in the application of prevention strategies. Further research is needed to understand how decision-makers can find the right balance between the choice of interventions, focus on high-risk populations, and geographical targeting to ensure the greatest impact of HIV prevention.