Applying the Effective Programme Coverage framework to assess gaps in HIV prevention programmes for female sex workers and men who have sex with men in Nairobi, Kenya: findings from an expanded Polling Booth Survey.

INTRODUCTION: Measuring the coverage of HIV prevention services for key populations (KPs) has consistently been a challenge for national HIV programmes. The current frameworks and measurement methods lack emphasis on effective coverage, occur infrequently, lack timeliness and limit the participation of KPs. The Effective Programme Coverage framework, which utilizes a programme science approach, provides an opportunity to assess gaps in various coverage domains and explore the underlying reasons for these gaps, in order to develop targeted solutions. We have demonstrated the application of this framework in partnership with the KP community in Nairobi, Kenya, using an expanded Polling Booth Survey (ePBS) method. METHODS: Data were collected between April and May 2023 among female sex workers (FSWs) and men who have sex with men (MSM) using (a) PBS, (b) bio-behavioural survey and (c) focus group discussions. Data collection and analysis involved both KP community and non-community researchers. Descriptive analysis was performed, and proportions were used to assess the programme coverage gaps. The data were weighted to account for the sampling design and unequal selection probabilities. Thematic analysis was conducted on the qualitative data. RESULTS: The condom programme for FSW and MSM had low availability (60.2% and 50.9%), contact (68.8% and 65.9%) and utilization (52.1% and 43.9%) coverages. The pre-exposure prophylaxis (PrEP) programme had very low utilization coverage for FSW and MSM (4.4% and 2.8%), while antiretroviral therapy utilization coverage was higher (86.6% and 87.7%). Reasons for coverage gaps included a low peer educator-to-peer ratio, longer distance to the clinics, shortage of free condoms supplied by the government, experienced and anticipated side effects related to PrEP, and stigma and discrimination experienced in the facilities. CONCLUSIONS: The Effective Programme Coverage framework allows programmes to assess coverage gaps and develop solutions and a research agenda targeted at specific domains of coverage with large gaps. The ePBS method works well in collecting data to understand coverage gaps rapidly and allows for the engagement of the KP community.

Programme science: a route to effective coverage and population-level impact for HIV and sexually transmitted infection prevention.

Improvements in context-specific programming are essential to address HIV and other sexually transmitted and blood-borne infection epidemics globally. A programme science approach emphasises the need for context-specific evidence and knowledge, generated on an ongoing basis, to inform timely and appropriate programmatic decisions. We aim to accelerate and improve the use of embedded research, inquiry, and learning to optimise population-level impact of public health programmes and to introduce an effective programme coverage framework as one tool to facilitate this goal. The framework was developed in partnership with public health experts in HIV and sexually transmitted and blood-borne infections through several workshops and meetings. The framework is a practice-based tool that centres on the use of data from iterative cycles of programme-embedded research and learning, as well as routine programme monitoring, to refine the strategy and implementation of a programme. This programme science approach aims to reduce programme coverage gaps, to optimise impact at the population level, and to achieve effective coverage. This framework should facilitate the generation of programme-embedded research and learning agendas to inform resource allocation, optimise population-level impact, and achieve equitable and effective programme coverage.

Reductions in HIV incidence are likely to increase the importance of key population programmes for HIV control in sub-Saharan Africa.

INTRODUCTION: An efficient HIV response requires that resources be focussed on effective interventions for those most at risk of acquiring and transmitting infection. As HIV epidemics evolve the distribution of HIV across key and other populations will change. Here, the epidemiological concepts underpinning these changes are described and the importance of appropriate allocation of effective interventions is discussed. DISCUSSION: In many sub-Saharan African countries HIV epidemics have been categorized as "generalized," and HIV testing, treatment and prevention interventions have focussed on the "general" population. As HIV epidemics are better controlled the relative importance of "key" populations will increase, dominating the ongoing burden of disease and providing the potential for repeated outbreaks of HIV if interventions are relaxed. The basic reproductive number (R0 ) describes the potential for an infectious disease to spread at the boundary of invasion or elimination, whereas the effective reproduction number (Rt ) describes the current potential for spread. Heterogeneity in risk means that while Rt is temporarily below one and prevalence declining, the R0 can remain above one, preventing eventual elimination. Patterns of HIV acquisition are often used to guide interventions but inadequately capture the transmission dynamics of the virus and the most efficient approach to controlling HIV. Risks for HIV acquisition are not identical to risks for HIV transmission and will change depending on the epidemiological context. In addition to the challenges in measuring HIV transmission dynamics, there is a tension between using epidemiology to drive the HIV response and the social and political realities constraining how programmes and providers can practically and appropriately focus on key populations and maintain political support. In addition to being well focussed, interventions need to be effective and cost-effective, which requires a better understanding of packages of interventions rather than specific tools. CONCLUSIONS: Continued control of HIV will increasingly rely on resources, programmes and interventions supporting key populations. Current epidemiological and programmatic approaches for key populations in sub-Saharan Africa are insufficient with a need for an improved understanding of local epidemiology and the effectiveness of interventions.

The potential role of long-acting injectable cabotegravir-rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.

BACKGROUND: The use of a combination of the integrase inhibitor, cabotegravir, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form is being considered as an antiretroviral treatment option for people with HIV in sub-Saharan Africa. We aimed to model the effects of injectable cabotegravir-rilpivirine to help to inform its potential effectiveness and cost-effectiveness under different possible policies for its introduction. METHODS: We used an existing individual-based model of HIV to predict the effects of introducing monthly injections of cabotegravir-rilpivirine for people with HIV in low-income settings in sub-Saharan Africa. We evaluated policies in the context of 1000 setting scenarios that reflected characteristics of HIV epidemics and programmes in sub-Saharan Africa. We compared three policies for introduction of injectable cabotegravir-rilpivirine with continued use of dolutegravir-based oral regimens for: all individuals on antiretroviral therapy (ART); individuals with a recently measured viral load of more than 1000 copies per mL (signifying poor adherence to oral drugs, and often associated with drug resistance); and individuals with a recently measured viral load of less than 1000 copies per mL (a group with a lower prevalence of pre-existing drug resistance). We also did cost-effectiveness analysis, taking a health system perspective over a 10 year period, with 3% discounting of disability-adjusted life-years (DALYs) and costs. A cost-effectiveness threshold of US$500 per DALY averted was used to establish if a policy was cost-effective. FINDINGS: In our model, all policies involving the introduction of injectable cabotegravir-rilpivirine were predicted to lead to an increased proportion of people with HIV on ART, increased viral load suppression, and decreased AIDS-related mortality, with lesser benefits in people with a recently measured viral load of less than 1000 copies per mL. Its introduction is also predicted to lead to increases in resistance to integrase inhibitors and non-nucleoside reverse transcriptase inhibitors if introduced in all people with HIV on ART or in those with a recently measured viral load of less than 1000 copies per mL, but to a lesser extent if introduced in people with more than 1000 copies per mL due to concentration of its use in people less adherent to oral therapy. Consistent with the effect on AIDS-related mortality, all approaches to the introduction of injectable cabotegravir-rilpivirine are predicted to avert DALYs. Assuming a cost of $120 per person per year, use of this regimen in people with a recently measured viral load of more than 1000 copies per mL was borderline cost-effective (median cost per DALY averted across setting scenarios $404). The other approaches considered for its use are unlikely to be cost-effective unless the cost per year of injectable cabotegravir-rilpivirine is considerably reduced. INTERPRETATION: Our modelling suggests that injectable cabotegravir-rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives. FUNDING: Bill & Melinda Gates Foundation, including through the HIV Modelling Consortium (OPP1191655).

Strengthening measurement and performance of HIV prevention programmes.

Indicators for the measurement of programmes for the primary prevention of HIV are less aligned than indicators for HIV treatment, which results in a high burden of data collection, often without a clear vision for its use. As new evidence becomes available, the opportunity arises to critically evaluate the way countries and global bodies monitor HIV prevention programmes by incorporating emerging data on the strength of the evidence linking various factors with HIV acquisition, and by working to streamline indicators across stakeholders to reduce burdens on health-care systems. Programmes are also using new approaches, such as targeting specific sexual networks that might require non-traditional approaches to measurement. Technological advances can support these new directions and provide opportunities to use real-time analytics and new data sources to more effectively understand and adapt HIV prevention programmes to reflect population movement, risks, and an evolving epidemic.

High variability in the measurement of HIV primary prevention activities and outcomes.

INTRODUCTION: While there is a global consensus on monitoring Human Immunodeficiency Virus (HIV) treatment progress, there has been less attention to the degree of consistency of the measurement of HIV prevention programmes-and the global prevention response is not on-track to achieve 2020 goals. In this paper, we assess the degree of variability in primary prevention indicators selected by national strategic plans (NSPs) and global stakeholder monitoring and evaluation (M&E) strategies. METHODS: We obtained the most recent NSPs from low and middle income Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track countries, and M&E documents from The Global Fund to Fight AIDS, Tuberculosis and Malaria (The Global Fund), President's Emergency Plan for AIDS Relief (PEPFAR), UNAIDS, the Global HIV Prevention Coalition and the World Health Organization (WHO). We extracted HIV primary prevention indicators from each document, standardized and aggregated them by age/ sex, categorized indicators by topic, and evaluated the frequency of matched indicators between countries and stakeholders. Data were collected between February and April of 2019. RESULTS: Twenty-one NSPs and five global stakeholder documents were assessed; 736 primary prevention indicators were identified; 284 remained following standardization and aggregation. NSPs contained from 3 to 48 primary prevention indicators, with an average of 23; categories included: HIV education and outreach (17.6%), testing (17.3%) and condom use (16.2%). Of unique national indicators, only 34% was shared between two or more countries. Sixty-nine per cent was applied in a single country only. 56% of NSP indicators did not appear in any global stakeholder document. Conversely, 42% of global indicators did not appear in any surveyed NSPs. Within global indicators, 63% was only measured by one global body, and no single indicator was measured by all five. CONCLUSIONS: These analyses reveal a lack of consensus both between and within countries' and global stakeholders' measurement of HIV prevention. Though some variability is expected, these findings point to a need to refocus attention on achieving greater consensus on a global measurement framework for HIV prevention.

Evidence of sociodemographic heterogeneity across the HIV treatment cascade and progress towards 90-90-90 in sub-Saharan Africa - a systematic review and meta-analysis.

INTRODUCTION: Heterogeneity of sociodemographics and risk behaviours across the HIV treatment cascade could influence the public health impact of universal ART in sub-Saharan Africa if those not virologically suppressed are more likely to be part of a risk group contributing to onward infections. Sociodemographic and risk heterogeneity across the treatment cascade has not yet been comprehensively described or quantified and we seek to systematically review and synthesize research on this topic among adults in Africa. METHODS: We conducted a systematic review of peer-reviewed literature in Embase and MEDLINE databases as well as grey literature sources published in English between 2014 and 2018. We included studies that included people living with HIV (PLHIV) aged ≥15 years, and reported a 90-90-90 outcome: awareness of HIV-positive status, ART use among those diagnosed or viral suppression among those on ART. We summarized measures of association between sociodemographics, within each outcome, and as a composite measure of population-wide viral suppression. RESULTS AND DISCUSSION: From 3533 screened titles, we extracted data from 92 studies (50 peer-reviewed, 42 grey sources). Of included studies, 32 reported on awareness, 53 on ART use, 32 on viral suppression and 23 on population-wide viral suppression. The majority of studies were conducted in South Africa, Uganda, and Malawi and reported data for age and gender. When stratified, PLHIV ages 15 to 24 years had lower median achievement of the treatment cascade (60-49-81), as compared to PLHIV ≥25 years (70-63-91). Men also had lower median achievement of the treatment cascade (66-72-85), compared to women (79-76-89). For population-wide viral suppression, women aged ≥45 years had achieved the 73% target, while the lowest medians were among 15- to 24-year-old men (37%) and women (49%). CONCLUSIONS: Considerable heterogeneity exists by age and gender for achieving the HIV 90-90-90 treatment goals. These results may inform delivery of HIV testing and treatment in sub-Saharan Africa, as targeting youth and men could be a strategic way to maximize the population-level impact of ART.

Vaccination With Moderate Coverage Eradicates Oncogenic Human Papillomaviruses If a Gender-Neutral Strategy Is Applied.

BACKGROUND: Human papillomavirus (HPV) vaccination of girls with very high (>90%) coverage has the potential to eradicate oncogenic HPVs, but such high coverage is hard to achieve. However, the herd effect (HE) depends both on the HPV type and the vaccination strategy. METHODS: We randomized 33 Finnish communities into gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and hepatitis B virus vaccination arms. In 2007-2010, 11 662 of 20 513 of 40 852 of 39 420 resident boys/girls from 1992 to 1995 birth cohorts consented. In 2010-2014, cervicovaginal samples from vaccinated and unvaccinated girls at age 18.5 years were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Vaccine efficacy for vaccinated girls, HE for unvaccinated girls, and the protective effectiveness (PE) for all girls were estimated. We extended the community-randomized trial results about vaccination strategy with mathematical modeling to assess HPV eradication. RESULTS: The HE and PE estimates in the 1995 birth cohort for HPV18/31/33 were significant in the gender-neutral arm and 150% and 40% stronger than in the girls-only arm. Concordantly, HPV18/31/33 eradication was already predicted in adolescents/young adults in 20 years with 75% coverage of gender-neutral vaccination. With the 75% coverage, eventual HPV16 eradication was also predicted, but only with the gender-neutral strategy. CONCLUSIONS: Gender-neutral vaccination is superior for eradication of oncogenic HPVs.

Demographic and risk group heterogeneity across the UNAIDS 90-90-90 targets: a systematic review and meta-analysis protocol.

BACKGROUND: Despite policies for universal HIV testing and treatment (UTT) regardless of CD4 count, there are still 1.8 million new HIV infections and 1 million AIDS-related deaths annually. The UNAIDS 90-90-90 goals target suppression of HIV viral load in 73% of all HIV-infected people worldwide by 2030. However, achieving these targets may not lead to expected reductions in HIV incidence if the remaining 27% (persons with unsuppressed viral load) are the drivers of HIV transmission through high-risk behaviors. We aim to conduct a systematic review and meta-analysis to understand the demographics, mobility, geographic distribution, and risk profile of adults who are not virologically suppressed in sub-Saharan Africa in the era of UTT. METHODS: We will review the published and grey literature for study sources that contain data on demographic and behavioral strata of virologically suppressed and unsuppressed populations since 2014. We will search PubMed and Embase using four sets of search terms tailored to identify characteristics associated with virological suppression (or lack thereof) and each of the individual 90-90-90 goals. Record screening and data abstraction will be done independently and in duplicate. We will use random effects meta-regression analyses to estimate the distribution of demographic and risk features among groups not virologically suppressed and for each individual 90-90-90 goal. DISCUSSION: The results of our review will help elucidate factors associated with failure to achieve virological suppression in sub-Saharan Africa, as well as factors associated with failure to achieve each of the 90-90-90 goals. These data will help quantify the population-level effects of current HIV treatment interventions to improve strategies for maximizing virological suppression and ending the HIV epidemic. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018089505 .

Gender-neutral vaccination provides improved control of human papillomavirus types 18/31/33/35 through herd immunity: Results of a community randomized trial (III).

With optimal strategy, human papillomavirus (HPV) vaccines have the potential to control HPV. We have assessed vaccine efficacy (VE), herd effect (HE) of HPV vaccination and overall protective effectiveness (PE) against high-risk HPV infections by HPV type and vaccination strategy in a community-randomized trial using the bivalent HPV16/18 vaccine. We randomized 33 communities to gender-neutral HPV vaccination (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Entire 1992-1995 male (40,852) and female (39,420) birth cohorts were invited, and 11,662 males and 20,513 females vaccinated with 20-30% and 45% coverage in 2007-2010. During 2010-2014, 11,396 cervicovaginal samples were collected from 13,545 18.5-year-old attendees. HPV typing was performed by a high-throughput PCR. VE was calculated for HPV vaccinated women and HE for non-HPV-vaccinated women, using the HBV vaccinated, for HE all non-HPV vaccinated, Arm C women as controls. PE was calculated as coverage rate-weighted mean of VE + HE. HPV16/18/45 and 31/33/35 VEs varied between 86-94% and 30-66%, respectively. Only the gender-neutral vaccination provided significant HEs against HPV18 (61%) and HPV31 (72%) in the 1995 birth cohort-increased HEs against HPV33 (39%) and HPV35 (42%) were also observed. Due to the increased HEs, PEs for HPV16/18/45 and HPV31/33/35 were comparable in the gender-neutral arm 1995 birth cohort. High vaccine efficacy against HPV16/18/45 and, gender-neutral vaccination-enforced, herd effect against HPV18/31/33/35 by the bivalent vaccine rapidly provides comparable overall protective effectiveness against six oncogenic HPV types: 16/18/31/33/35/45.

Evaluation of HPV type-replacement in unvaccinated and vaccinated adolescent females-Post-hoc analysis of a community-randomized clinical trial (II).

Efficacy of human papillomavirus (HPV) vaccines promises to control HPV infections. However, HPV vaccination programs may lay bare an ecological niche for non-vaccine HPV types. We evaluated type-replacement by HPV type and vaccination strategy in a community-randomized trial executed in HPV vaccination naïve population. Thirty-three communities were randomized to gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Resident 1992-95 born boys (40,852) and girls (39,420) were invited. 11,662 boys and 20,513 girls were vaccinated with 20-30% and 45-48% coverage, respectively. HPV typing of 11,396 cervicovaginal samples was performed by high throughput PCR. Prevalence ratios (PR) between arms and ranked order of HPV types and odds ratio (OR) for having multiple HPV types in HPV16 or 18/45 positive individuals were calculated. The ranked order of HPV types did not significantly differ between arms or birth cohorts. For the non-HPV vaccinated 1992-1993 birth cohorts increased PR, between the gender-neutral intervention versus control arms for HPV39 (PRA 1.84, 95% CI 1.12-3.02) and HPV51 (PRA 1.56, 95% CI 1.11-2.19) were observed. In the gender-neutral arm, increased clustering between HPV39 and the vaccine-covered HPV types 16 or 18/45 (ORA16 = 5.1, ORA18/45 = 11.4) was observed in the non-HPV vaccinated 1994-1995 birth cohorts. Comparable clustering was seen between HPV51 and HPV16 or HPV18/45 (ORB16 = 4.7, ORB18/45 = 4.3), in the girls-only arm. In conclusion, definitively consistent postvaccination patterns of HPV type-replacement were not observed. Future occurrence of HPV39 and HPV51 warrant investigation.

[Prevalence of bacterial vaginosis and associated factors in twenty peruvian cities]. / Prevalencia de vaginosis bacteriana y factores asociados en veinte ciudades del Perú.

OBJETIVES.: To determine the prevalence of bacterial vaginosis (BV) and associated factors among 18-29-year-old women in 20 Peruvian cities using PREVEN project data. MATERIALS AND METHODS.: In this cross-sectional study, BV was defined using previously provided vaginal discharge samples on slides, which were Gram stained and observed under a microscope to determine the Nugent scores. A BV diagnosis was applied to samples with scores of 7-10. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were estimated using generalized linear models. RESULTS.: A total of 6,322 women participated in the epidemiological survey and provided vaginal swabs. The prevalence of BV was 23.7% (95% CI: 22.6-24.7) and was associated with a greater number of sexual partners in the last 12 months (PR: 1.22, 95% CI: 1.03-1.44, p=0.020 for two partners; PR: 1.46, 95% CI: 1.23-1.74, p<0.001 for three or more partners), not using a condom during last intercourse (PR: 1.16, 95% CI: 1.01-1.34, p=0.034), being a sierra resident (PR: 1.18, 95% CI: 1.05-1.31, p=0.004), and having abnormal vaginal discharge or a bad smell (PR: 1.20, 95% CI: 1.09-1.33, p<0.001). CONCLUSIONS.: The high prevalence of BV highlights the need to strengthen health services aimed at the detection and treatment of this condition.

Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile.

Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results not received, use of an approach that best facilitates retention on ART, and the ability to facilitate greater use of differentiated care, including through expanding coverage of testing availability.

Prevalencia de vaginosis bacteriana y factores asociados en veinte ciudades del Perú / Prevalence of bacterial vaginosis and associated factors in twenty peruvian cities

RESUMEN Objetivos. Determinar la prevalencia de vaginosis bacteriana (VB) y factores asociados en mujeres peruanas de 18 a 29 años de edad en 20 ciudades a partir de datos del proyecto PREVEN. Materiales y métodos. Estudio de tipo transversal, la definición de VB se realizó previa selección de una muestra de secreción vaginal en una lámina portaobjetos. Las láminas fueron teñidas usando la tinción Gram para ser observadas al microscopio usando el puntaje de Nugent, el diagnóstico de VB se aplicó a los puntajes 7-10. Se estimaron razones de prevalencias (RP) y sus intervalos de confianza al 95% (IC 95%) mediante el uso de modelos lineales generalizados. Resultados. Un total de 6322 mujeres contestaron la encuesta epidemiológica y proporcionaron muestras vaginales. La prevalencia de VB fue de 23,7% (IC95%: 22,6-24,7) y se asoció con tener un mayor número de parejas sexuales en los últimos 12 meses (RP: 1,22, IC 95%: 1,03-1,44, p=0,020; para dos parejas y RP: 1,46, IC 95%: 1,23-1,74, p<0,001 para tres o más parejas), no usar condón en la última relación sexual (RP: 1,16, IC 95%: 1,01-1,34, p=0,034), ser residente de la sierra (RP: 1,18, IC 95%: 1,05-1,31, p=0,004) y tener flujo vaginal anormal o con mal olor (RP: 1,20, IC 95%: 1,09-1,33, p<0,001). Conclusiones. La alta prevalencia de VB encontrada remarca la necesidad de fortalecer los servicios de salud para la detección y tratamiento de esta condición.

ABSTRACT Objetives. To determine the prevalence of bacterial vaginosis (BV) and associated factors among 18-29-year-old women in 20 Peruvian cities using PREVEN project data. Materials and Methods. In this cross-sectional study, BV was defined using previously provided vaginal discharge samples on slides, which were Gram stained and observed under a microscope to determine the Nugent scores. A BV diagnosis was applied to samples with scores of 7-10. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were estimated using generalized linear models. Results. A total of 6,322 women participated in the epidemiological survey and provided vaginal swabs. The prevalence of BV was 23.7% (95% CI: 22.6-24.7) and was associated with a greater number of sexual partners in the last 12 months (PR: 1.22, 95% CI: 1.03-1.44, p=0.020 for two partners; PR: 1.46, 95% CI: 1.23-1.74, p<0.001 for three or more partners), not using a condom during last intercourse (PR: 1.16, 95% CI: 1.01-1.34, p=0.034), being a sierra resident (PR: 1.18, 95% CI: 1.05-1.31, p=0.004), and having abnormal vaginal discharge or a bad smell (PR: 1.20, 95% CI: 1.09-1.33, p<0.001). Conclusions. The high prevalence of BV highlights the need to strengthen health services aimed at the detection and treatment of this condition.

Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study.

BACKGROUND: Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years. METHODS: We developed a deterministic compartmental model of heterosexual HIV transmission in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, early antiretroviral therapy [ART] initiation for all [including increased HIV testing and counselling activities], and oral pre-exposure prophylaxis [PrEP]), the introduction of new interventions in the medium term (offering intravaginal rings, long-acting injectable antiretroviral drugs) and long term (vaccine, broadly neutralising antibodies [bNAbs]). We examined how available resources could be allocated across these interventions to achieve maximum impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up. FINDINGS: If all interventions are available, the optimum mix would place great emphasis on the following: scale-up of male circumcision and early ART initiation with outreach testing, as these are available immediately and assumed to be low cost and highly efficacious; intravaginal rings targeted to sex workers; and vaccines, as these can achieve a large effect if scaled up even if imperfectly efficacious. The optimum mix would rely less on longer term developments, such as long-acting antiretroviral drugs and bNAbs, unless the costs of these reduced. However, if impossible to scale up existing interventions to the extent assumed, emphasis on oral PrEP, intravaginal rings, and long-acting antiretroviral drugs would increase. The long-term effect on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine. INTERPRETATION: With current information, a strategic approach in which limited resources are used to maximise prevention impact would focus on strengthening the scale-up of existing interventions, while pursuing a workable vaccine and developing other approaches that can be used if further scale-up of existing interventions is limited. FUNDING: Bill & Melinda Gates Foundation.

The HIV prevention cascade: integrating theories of epidemiological, behavioural, and social science into programme design and monitoring.

Theories of epidemiology, health behaviour, and social science have changed the understanding of HIV prevention in the past three decades. The HIV prevention cascade is emerging as a new approach to guide the design and monitoring of HIV prevention programmes in a way that integrates these multiple perspectives. This approach recognises that translating the efficacy of direct mechanisms that mediate HIV prevention (including prevention products, procedures, and risk-reduction behaviours) into population-level effects requires interventions that increase coverage. An HIV prevention cascade approach suggests that high coverage can be achieved by targeting three key components: demand-side interventions that improve risk perception and awareness and acceptability of prevention approaches; supply-side interventions that make prevention products and procedures more accessible and available; and adherence interventions that support ongoing adoption of prevention behaviours, including those that do and do not involve prevention products. Programmes need to develop delivery platforms that ensure these interventions reach target populations, to shape the policy environment so that it facilitates implementation at scale with high quality and intensity, and to monitor the programme with indicators along the cascade.

HIV Prevention 2020: a framework for delivery and a call for action.

Although effective programmes are available and several countries have seen substantial declines in new HIV infections, progress in the reduction of adult HIV incidence has been slower than expected worldwide and many countries have not had large decreases in new infections in adults despite large reductions in paediatric infections. Reasons for slow progress include inadequate commitment, investment, focus, scale, and quality of implementation of prevention and treatment interventions. The UNAIDS-Lancet Commission on Defeating AIDS-Advancing Global Health reported that the provision of large-scale, effective HIV prevention programmes has failed and called on stakeholders to "get serious about HIV prevention". An ambitious worldwide target has been set by UNAIDS to reduce new infections below 500 000 by 2020-a 75% reduction from 2010. Models show that such a reduction requires a combination of primary prevention interventions and preventative effects of treatment. Achievement of the target will require more effective delivery of HIV prevention for sufficient coverage in populations at greatest risk of infection ensuring that interventions that have proved effective are made available, barriers to their uptake are overcome, demand is created, and use is consistent and occurs at the right scale with high coverage. This paper discusses how programmatic targets for prevention in a worldwide plan could be used to re-energise the HIV prevention approach. A management framework is proposed outlining global, regional, national, and subnational actions and is summarised in a call for action on HIV prevention for 2020.

Home testing and counselling to reduce HIV incidence in a generalised epidemic setting: a mathematical modelling analysis.

BACKGROUND: Home HIV testing and counselling (HTC) achieves high levels of HIV testing and linkage to care. Periodic home HTC, particularly targeted to those with high HIV viral load, might facilitate expansion of antiretroviral therapy (ART) coverage. We used a mathematical model to assess the effect of periodic home HTC programmes on HIV incidence in KwaZulu-Natal, South Africa. METHODS: We developed a dynamic HIV transmission model with parameters, primary cost data, and measures of viral suppression collected from a prospective study of home HTC in KwaZulu-Natal. In our model, we assumed home HTC took place every 5 years with ART initiation for people with CD4 counts of 350 cells per µL or less. For individuals with CD4 counts of more than 350 cells per µL, we compared increasing ART coverage for those with 350-500 cells per µL with initiating treatment for those who have viral loads of more than 10 000 copies per mL. FINDINGS: Maintaining the presently observed level of 36% viral suppression in HIV-positive people, HIV incidence decreases by 33·8% over 10 years. Home HTC every 5 years with linkage to care with ART initiation at CD4 counts of 350 cells per µL or less reduces HIV incidence by 40·6% over 10 years. Expansion of ART to people with CD4 counts of more than 350 cells per µL who also have a viral load of 10 000 copies per mL or more decreases HIV incidence by 51·6%, and this was the most cost-effective strategy for prevention of HIV infections at US$2960 per infection averted. Expansion of ART eligibility CD4 counts of 350-500 cells per µL is cost-effective at $900 per quality-adjusted life-year gained. Following health economic guidelines, expansion of ART use to individuals who have viral loads of more than 10 000 copies per mL among those with CD4 counts of more than 350 cells per µL was cost-effective to reduce HIV-related morbidity. INTERPRETATION: Our results show that province-wide home HTC every 5 years can be a cost-effective strategy to increase ART coverage and reduce HIV burden. Expanded ART initiation criteria that includes individuals with high viral load will improve the effectiveness of home HTC in linking individuals to ART who are at high risk of transmitting HIV, thereby preventing morbidity and onward transmission. FUNDING: National Institutes of Health.