Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis in South Africa based on the HPTN 083 and HPTN 084 trials: a modelled economic evaluation and threshold analysis.

BACKGROUND: Long-acting injectable cabotegravir, a drug taken every 2 months, has been shown to be more effective at preventing HIV infection than daily oral tenofovir disoproxil fumarate and emtricitabine, but its cost-effectiveness in a high-prevalence setting is not known. We aimed to estimate the incremental cost-effectiveness of long-acting injectable cabotegravir compared with tenofovir disoproxil fumarate and emtricitabine in South Africa, using methods standard to government planning, and to determine the threshold price at which long-acting injectable cabotegravir is as cost-effective as tenofovir disoproxil fumarate and emtricitabine. METHODS: In this modelled economic evaluation and threshold analysis, we updated a deterministic model of the South African HIV epidemic with data from the HPTN 083 and HPTN 084 trials to evaluate the effect of tenofovir disoproxil fumarate and emtricitabine and long-acting injectable cabotegravir provision to heterosexual adolescents and young women and men aged 15-24 years, female sex workers, and men who have sex with men. We estimated the average intervention cost, in 2021 US$, using ingredients-based costing, and modelled the cost-effectiveness of two coverage scenarios (medium or high, assuming higher uptake of long-acting injectable cabotegravir than tenofovir disoproxil fumarate and emtricitabine throughout) and, for long-acting injectable cabotegravir, two duration subscenarios (minimum: same pre-exposure prophylaxis duration as for tenofovir disoproxil fumarate and emtricitabine; maximum: longer duration than tenofovir disoproxil fumarate and emtricitabine) over 2022-41. FINDINGS: Across long-acting injectable cabotegravir scenarios, 15-28% more new HIV infections were averted compared with the baseline scenario (current tenofovir disoproxil fumarate and emtricitabine roll-out). In scenarios with increased coverage with oral tenofovir disoproxil fumarate and emtricitabine, 4-8% more new HIV infections were averted compared with the baseline scenario. If long-acting injectable cabotegravir drug costs were equal to those of tenofovir disoproxil fumarate and emtricitabine for the same 2-month period, the incremental cost of long-acting injectable cabotegravir to the HIV programme was higher than that of tenofovir disoproxil fumarate and emtricitabine (5-10% vs 2-4%) due to higher assumed uptake of long-acting injectable cabotegravir. The cost per infection averted was $6053-6610 (tenofovir disoproxil fumarate and emtricitabine) and $4471-6785 (long-acting injectable cabotegravir). The cost per long-acting cabotegravir injection needed to be less than twice that of a 2-month supply of tenofovir disoproxil fumarate and emtricitabine to remain as cost-effective, with threshold prices ranging between $9·03 per injection (high coverage; maximum duration) and $14·47 per injection (medium coverage; minimum duration). INTERPRETATION: Long-acting injectable cabotegravir could potentially substantially change HIV prevention. However, for its implementation to be financially feasible across low-income and middle-income countries with high HIV incidence, long-acting injectable cabotegravir must be reasonably priced. FUNDING: United States Agency for International Development, The Bill & Melinda Gates Foundation.

The impact of conditional cash transfers for HIV prevention on peer relationships: perspectives from female recipients and non-recipients in HPTN 068.

CCTs are currently being explored for HIV prevention among adolescent girls and young women (AGYW) in Southern Africa. However, little is known about how CCT geared towards adolescents' influence peer relationships, despite evidence that peer relationships form a critical part of development in adolescence. This article presents findings from a qualitative study that explored CCT recipients' and non-recipients' perspectives on the impact of CCTs paid to AGYW on peer relationships.HPTN 068 was a randomised controlled trial that assessed whether providing CCT to AGYW and their households reduces AGYW's risk of acquiring HIV. As part of this trial, we conducted interviews and focus group discussions with sub-samples of AGYW (n = 39), who were both cash recipients and non-recipients. Through content analysis, we explored ways in which the CCT positively or negatively impacted on peer relationships.From the recipients' viewpoint, the CCT improved their social standing within their peer groups. It facilitated peer identity and promoted social connectedness among AGYW receiving the CCT. Receipt of the CCT enabled AGYW to resemble and behave like their peers who had money, allowing their poverty to become "invisible". The CCT facilitated social interactions, information sharing, and instrumental social support among AGYW. CCT recipients experienced an increase in their social capital, evident in their ability to network, share, and reciprocate with others. However, the CCT also evoked negative emotions such as jealousy, anxiety, and resentment among non-recipients and led to a deterioration of personal relationships.CCTs have enormous benefits for AGYW, but they may also have a negative impact on peer relationships. The implementation of HIV prevention interventions focused on structural drivers needs to be conscious of these dynamics and ensure that the negative consequences do not outweigh benefits.

Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022.

The World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cervical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low- and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of global expert consultations to lay the groundwork for understanding the potential value of TxV in the context of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and findings from the expert consultations. Experts identified several ways in which TxV might address challenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use-cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.

Cost-Effectiveness of HIV Pre-exposure Prophylaxis Among Heterosexual Men in South Africa: A Cost-Utility Modeling Analysis.

INTRODUCTION: Heterosexual men are not considered a key population in the HIV response and are mostly absent from pre-exposure prophylaxis (PrEP) studies to date. Yet, South African men face considerable HIV risk. We estimate the incremental cost-effectiveness of providing oral PrEP, injectable PrEP, or a combination of both to heterosexual South African men to assess whether providing PrEP would efficiently use resources. METHODS: Epidemiological and costing models estimated the one-year costs and outcomes associated with PrEP use in 3 scenarios. PrEP uptake was estimated for younger (aged 18-24) and older (aged 25-49) men using a discrete choice experiment. Scenarios were compared with a baseline scenario of male condom use, while a health system perspective was used to estimate discounted lifetime costs averted per HIV infection. PrEP benefit was estimated in disability-adjusted life years (DALYs) averted. Uncertainty around the estimated incremental cost-effectiveness ratios (ICERs) was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: No PrEP intervention scenarios were cost-effective for both age groups at a willingness-to-pay threshold of $1175/DALY averted. The lowest ICER ($2873/DALY averted) was for the provision of oral PrEP to older men, although probability of cost-effectiveness was just 0.26%. Results found that ICERs were sensitive to HIV incidence and antiretroviral coverage. CONCLUSIONS: This study estimates that providing PrEP to heterosexual South African men is not cost-effective at current cost-effectiveness thresholds. Given the ICERs' sensitivity to several variables, alongside the heterogeneity of HIV infection among South African men, PrEP may be cost-effective for older men with high incidence and other subgroups based on locality and race. We recommend further investigation to better identify and target these groups.

Men's perspectives on the impact of female-directed cash transfers on gender relations: Findings from the HPTN 068 qualitative study.

BACKGROUND: HIV is an inherently gendered disease in eastern and southern Africa, not only because more women than men are infected, but also because socially constructed gender norms work to increase women's HIV-infection risk. The provision of cash transfers to young women alone in such a context adds another dimension to already existing complex social relations where patriarchal values are entrenched, gender inequality is the norm, and violence against women and girls is pervasive. It raises concerns about complicating young women's relationships with their male partners or possibly even setting them up for more violence. In our attempt to understand how cash transfers influence social relations in the context of a trial among young women in South Africa, we used qualitative data collected during the trial to explore men's perceptions of the impact of cash transfers on male-female relationships, both intimate and platonic, peer relationships. METHOD: Between April 2012 and August 2015, we conducted focus group discussions (n = 12) and interviews (n = 20) with the male peers and intimate partners of young women aged 13-20 years, who were participating in a phase III randomised controlled trial of CTs for HIV prevention in Mpumalanga, South Africa. A thematic content analysis approach was used to analyse the data. The codebook was developed on the basis of the topic guides, with additional codes added inductively as they emerged from the data. RESULTS: Intimate partners were older (range 20-32 years) and more likely to be working than the male peers. Both intimate partners and male peers were supportive of the CT trial targeting young women; younger peers however expressed some concerns that the money might diminish their power and status in relationships. HIV testing requirements associated with the trial appeared to have improved communication about sex and HIV in intimate relationships, with some women even encouraging their partners to go for an HIV test. CONCLUSION: CTs provide AGYW with a measure of autonomy and power to contribute in their gendered relationships, albeit in limited ways. However, there is potential for CTs to have a negative impact on male-female relationships if the cash received by AGYW is equal to or greater than the income earned by their male counterparts or sexual partners.

Assessment of adolescent and youth friendly services in primary healthcare facilities in two provinces in South Africa.

BACKGROUND: Health services for adolescents are increasingly recognised as a priority in low- and middle-income countries (LMICs). The Adolescent and Youth Friendly Service (AYFS) approach has been promoted in South Africa by the National Department of Health and partners, as a means of standardising the quality of adolescent health services in the country. The objective of this paper is to detail the evaluation of AYFS against defined standards to inform initiatives for strengthening these services. METHODS: A cross-sectional assessment of AYFS was carried out in 14 healthcare facilities in a sub-district of Gauteng Province and 16 in a sub-district in North West Province, South Africa. Data on adolescent care and service management systems were collected through interviews with healthcare providers, non-clinical staff and document review. Responses were scored using a tool based on national and World Health Organisation criteria for ten AYFS standards. RESULTS: Mean scores for the ten standards showed substantial variation across facilities in the two sub-Districts, with Gauteng Province scoring lower than the North West for 9 standards. The sub-district median for Gauteng was 38% and the North West 48%. In both provinces standards related to the general service delivery, such as Standards 4 and 5, scored above 75%. Assessment of services specifically addressing sexual, reproductive and mental health (Standard 3) showed that almost all these services were scored above 50%. Exploration of services related to psycho-social and physical assessments (Standard 8) demonstrated differences in the healthcare facilities' management of adolescents' presenting complaints and their comprehensive management including psycho-social status and risk profile. Additionally, none of the facilities in either sub-district was able to meet the minimum criteria for the five standards required for AYFS recognition. CONCLUSION: Facilities had the essential components for general service delivery in place, but adolescent-specific service provision was lacking. AYFS is a government priority, but additional support for facilities is needed to achieve the agreed standards. Meeting these standards could make a major contribution to securing adolescents' health, especially in preventing unintended pregnancies and HIV as well as improving psycho-social management.

The effect of HIV prevention products on incentives to supply condomless commercial sex among female sex workers in South Africa.

Evidence suggests that economic factors play an important role in commercial sex work, in particular that condomless sex commands a price premium relative to condom-protected sex. This paper explores whether the use of a new HIV prevention product, with 100% efficacy but modeled after pre-exposure prophylaxis (PrEP), could change the price and quantity of condomless commercial sex supplied. We collected stated preference data from 122 HIV-negative female sex workers in urban South Africa, using a repeated choice experiment to simulate the impact of using PrEP on choices. Results suggest that the price premium for condomless sex would decrease by 73% with PrEP use and the quantity of condomless sex is predicted to increase by a factor of 2.27. Act price does not significantly affect choices without protection but strongly influences choices under full HIV protection. The utility offered by condoms reduces by around 15% under PrEP use. Because new HIV prevention products do not protect against other STIs or pregnancy, the unintended consequences of introducing HIV prevention products should be closely monitored, whereas users should not face stigma or blame for reacting rationally to exogenous changes to market conditions.

The cost-effectiveness of multi-purpose HIV and pregnancy prevention technologies in South Africa.

INTRODUCTION: A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi-purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost-effectiveness of combinations of candidate multi-purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs). METHODS: We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost-effectiveness of five candidate co-formulated or co-provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end-users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability-adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis. RESULTS: At central incidence rates, all single- and multi-purpose scenarios modelled were cost-effective among FSWs and women aged 16-24, at a governmental willingness-to-pay threshold of $1175/DALY averted (range: $214-$810/DALY averted among non-dominant scenarios), however, none were cost-effective among women aged 25-49 (minimum $1706/DALY averted). The cost-effectiveness of products improved with additional protection from pregnancy. Estimates were sensitive to variation in incidence assumptions, but robust to other parameters. CONCLUSIONS: To the best of our knowledge, this is the first study to estimate the cost-effectiveness of a range of potential MPTs; suggesting that MPTs will be cost-effective among higher incidence FSWs or young women, but not among lower incidence older women. More work is needed to make attractive MPTs available to potential users who could use them effectively.

Cash transfer interventions for sexual health: meanings and experiences of adolescent males and females in inner-city Johannesburg.

BACKGROUND: In sub-Saharan Africa, there is growing interest in the use of cash transfer (CT) programs for HIV treatment and prevention. However, there is limited evidence of the consequences related to CT provision to adolescents in low-resourced urban settings. We explored the experiences of adolescents receiving CTs to assess the acceptability and unintended consequences of CT strategies in urban Johannesburg, South Africa. METHODS: We collected qualitative data during a pilot randomized controlled trial of three CT strategies (monthly payments unconditional vs. conditional on school attendance vs. a once-off payment conditional on a clinic visit) involving 120 adolescents aged 16-18 years old in the inner city of Johannesburg. Interviews were conducted in isiZulu, Sesotho or English with a sub-sample of 49 participants who adhered to study conditions, 6 months after receiving CT (280 ZAR/ 20 USD) and up to 12 months after the program had ended. Interviews were transcribed and translated by three fieldworkers. Codes were generated using an inductive approach; transcripts were initially coded based on emerging issues and subsequently coded deductively using Atlas.ti 7.4. RESULTS: CTs promoted a sense of independence and an adult social identity amongst recipients. CTs were used to purchase personal and household items; however, there were gender differences in spending and saving behaviours. Male participants' spending reflected their preoccupation with maintaining a public social status through which they asserted an image of the responsible adult. In contrast, female participants' expenditure reflected assumption of domestic responsibilities and independence from older men, with the latter highlighting CTs' potential to reduce transactional sexual partnerships. Cash benefits were short-lived, as adolescents reverted to previous behavior after the program's cessation. CONCLUSION: CT programs offer adolescent males and females in low-income urban settings a sense of agency, which is vital for their transition to adulthood. However, gender differences in the expenditure of CTs and the effects of ending CT programs must be noted, as these may present potential unintended risks.

Advancing STI priorities in the SDG era: priorities for action.

The Sustainable Development Goals present an opportunity to reimagine and then reconfigure the approach to controlling sexually transmitted infections (STIs). The predilection of STIs for women and for vulnerable populations means that services that ameliorate STIs, by their nature, enhance equity, a key focus of the goals. Given the considerable breadth and depth of the goals, it is important to locate points of convergence between the SDGs and STIs, further craft synergies with HIV and select a few population groups and settings to prioritise. There are many opportunities for STI aficionados in this era to advance the field and global control of these infections.

'Leaving no one behind': reflections on the design of community-based HIV prevention for migrants in Johannesburg's inner-city hostels and informal settlements.

BACKGROUND: Unmanaged urban growth in southern and eastern Africa has led to a growth of informal housing in cities, which are home to poor, marginalised populations, and associated with the highest HIV prevalence in urban areas. This article describes and reflects on the authors' experiences in designing and implementing an HIV intervention originally intended for migrant men living in single-sex hostels of inner-city Johannesburg. It shows how formative research findings were incorporated into project design, substantially shifting the scope of the original project. METHODS: Formative research activities were undertaken to better understand the demand- and supply-side barriers to delivering HIV prevention activities within this community. These included community mapping, a baseline survey (n = 1458) and client-simulation exercise in local public sector clinics. The intervention was designed and implemented in the study setting over a period of 18 months. Implementation was assessed by way of a process evaluation of selected project components. RESULTS: The project scope expanded to include women living in adjacent informal settlements. Concurrent sexual partnerships between these women and male hostel residents were common, and HIV prevalence was higher among women (56%) than men (24%). Overwhelmingly, hostel residents were internal migrants from another province, and most felt 'alienated' from the rest of the city. While men prioritised the need for jobs, women were more concerned about water, sanitation, housing and poverty alleviation. Most women (70%) regarded their community as unsafe (cf. 47% of men). In the final intervention, project objectives were modified and HIV prevention activities were embedded within a broader health and development focus. 'Community health clubs' were established to build residents' capacity to promote health and longer term well-being, and to initiate and sustain change within their communities. CONCLUSIONS: To improve efforts to address HIV in urban informal settings, intervention designers must acknowledge and engage with the priorities set by the marginalised communities that live here, which may well encompass more pressing issues associated with daily survival.

PrEP implementation research in Africa: what is new?

INTRODUCTION: Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings. DISCUSSION: In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self-efficacy, empowerment and social cohesion, with evidence-based individualized adherence support for PrEP, are most likely to be effective. CONCLUSIONS: Efficacy of tenfovir-based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa.

Preventing HIV among adolescents with oral PrEP: observations and challenges in the United States and South Africa.

INTRODUCTION: Adolescents and young adults aged <25 are a key population in the HIV epidemic, with very high HIV incidence rates in many geographic settings and a large number who have limited access to prevention services. Thus, any biomedical HIV prevention approach should prepare licensure and implementation strategies for young populations. Oral pre-exposure prophylaxis (PrEP) is the first antiretroviral-based prevention intervention with proven efficacy across many settings and populations, and regulatory and policy approvals at global and national levels are occurring rapidly. We discuss available data from studies in the United States and South Africa on the use of oral PrEP for HIV prevention in adolescent minors, along with some of the implementation challenges. DISCUSSION: Ongoing studies in the United States and South Africa among youth under the age of 18 should provide the safety data needed by the end of 2016 to contribute to licensure of Truvada as daily PrEP in adolescents. The challenges of completing these studies as well as foreseeable broader challenges highlighted by this work are presented. Adherence to daily PrEP is a greater challenge for younger populations, and poor adherence was associated with decreased efficacy in all PrEP trials. Individual-level barriers include limited familiarity with antiretroviral-based prevention, stigma, product storage, and social support. Structural challenges include healthcare financing for PrEP, clinician acceptability and comfort with PrEP delivery, and the limited youth-friendly health services available. These challenges are discussed in the context of the work done to date in the United States and South Africa, but will likely be magnified in the setting of limited resources in many other countries that are heavily impacted by HIV. CONCLUSIONS: Adolescent populations are particularly vulnerable to HIV, and oral PrEP in these populations is likely to have an impact on population-level HIV incidence. The challenges of disseminating an HIV biomedical prevention tool requiring daily usage in adolescents are formidable, but addressing these issues and starting dialogues will lay the groundwork for the many other HIV prevention tools now being developed and tested.

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.

Precision of the Kalon Herpes Simplex Virus Type 2 IgG ELISA: an international inter-laboratory assessment.

BACKGROUND: The commercial Kalon HSV-2 IgG ELISA is currently recommended for research use in sub-Saharan Africa because of its superior accuracy compared to other serologic assays. However, there are no data on key precision parameters of Kalon such as inter-operator variation, repeatability, and reproducibility, thus contributing to a barrier for its acceptance and use in clinical trials in sub-Saharan Africa. We evaluated the analytical and field precision of the Kalon HSV-2 IgG ELISA. METHODS: A total of 600 HIV-infected and uninfected serum samples from South Africa and Zambia, previously tested by the gold standard University of Washington HSV western blot (UW-WB), were tested using Kalon by two technologists in an United States reference laboratory. Aliquots of 183 samples were retested using Kalon by an on-site technologist in a South African laboratory and a Zambian laboratory. RESULTS: Intra-assay variation was below 10 %. Intra-assay, intra-laboratory, and inter-laboratory correlation and agreement were significantly high (p < 0.01). In comparison to the UW-WB, accurate performance of Kalon was reproducible by each operator and laboratory. Receiver operating characteristic curve analysis indicated high selectivity of Kalon in the overall study population (area under the curve = 0.95, 95%CI = 0.92-0.97). DISCUSSION: Kalon is a robust assay with high precision and reproducibility. Accordingly, operator errorlikely does not contribute to the variability observed in Kalon's specificity throughout sera from sub-Saharan Africa. CONCLUSIONS: In populations with optimal diagnostic accuracy, Kalon is a reliable stand-alone method for on-site HSV-2 IgG antibody detection.

Providing comprehensive health services for young key populations: needs, barriers and gaps.

INTRODUCTION: Adolescence is a time of physical, emotional and social transitions that have implications for health. In addition to being at high risk for HIV, young key populations (YKP) may experience other health problems attributable to high-risk behaviour or their developmental stage, or a combination of both. METHODS: We reviewed the needs, barriers and gaps for other non-HIV health services for YKP. We searched PubMed and Google Scholar for articles that provided specific age-related data on sexual and reproductive health; mental health; violence; and substance use problems for adolescent, youth or young sex workers, men who have sex with men, transgender people, and people who inject drugs. RESULTS: YKP experience more unprotected sex, sexually transmitted infections including HIV, unintended pregnancy, violence, mental health disorders and substance use compared to older members of key populations and youth among the general population. YKP experience significant barriers to accessing care; coverage of services is low, largely because of stigma and discrimination experienced at both the health system and policy levels. DISCUSSION: YKP require comprehensive, integrated services that respond to their specific developmental needs, including health, educational and social services within the context of a human rights-based approach. The recent WHO Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations are an important first step for a more comprehensive approach to HIV programming for YKP, but there are limited data on the effective delivery of combined interventions for YKP. Significant investments in research and implementation will be required to ensure adequate provision and coverage of services for YKP. In addition, greater commitments to harm reduction and rights-based approaches are needed to address structural barriers to access to care.

Estimating the cost-effectiveness of pre-exposure prophylaxis to reduce HIV-1 and HSV-2 incidence in HIV-serodiscordant couples in South Africa.

OBJECTIVE: To estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa. METHODS: We incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter. RESULTS: We estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively--a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples. CONCLUSION: After a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.

A global study on the influence of neighborhood contextual factors on adolescent health.

PURPOSE: This study uses data collected as part of the Well-Being of Adolescents in Vulnerable Environments study to (1) compare the perceptions of neighborhood-level factors among adolescents across five different urban sites; (2) examine the associations between factors within the physical and social environments; and (3) examine the influence of neighborhood-level factors on two different health outcomes-violence victimization in the past 12 months and ever smoked. METHODS: Across five urban sites (Baltimore, New Delhi, Johannesburg, Ibadan, and Shanghai), 2,320 adolescents aged 15-19 years completed a survey using audio computer-assisted self-interview technology. To recruit adolescents, each site used a respondent-driven sampling method, which consisted of selecting adolescents as "seeds" to serve as the initial contacts for recruiting the entire adolescent sample. All analyses were conducted with Stata 13.1 statistical software, using complex survey design procedures. To examine associations between neighborhood-level factors and among our two outcomes, violence victimization and ever smoked, bivariate and multivariate analyses were conducted. RESULTS: Across sites, there was great variability in how adolescents perceived their neighborhoods. Overall, adolescents from Ibadan and Shanghai held the most positive perceptions about their neighborhoods, whereas adolescents from Baltimore and Johannesburg held the poorest. In New Delhi, despite females having positive perceptions about their safety and sense of social cohesion, they had the highest sense of fear and the poorest perceptions about their physical environment. The study also found that one of the most consistent neighborhood-level factors across sites and outcomes was witnessing community violence, which was significantly associated with smoking among adolescents in New Delhi and Johannesburg and with violence victimization across nearly every site except Baltimore. No other neighborhood-level factor exerted greater influence. CONCLUSIONS: This study confirms the important associations between perceptions of a neighborhood and adolescent health. At the same time, it demonstrates that not all neighborhood-level factors are associated with adolescent health outcomes in the same way across different urban contexts. Further longitudinal research is needed to examine the direction of causation between adolescent health neighborhood contexts and health outcomes and the reasons for why different urban contexts may exert varying levels of influence on the health of adolescents.