HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women.

Importance: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. Objective: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. Design, Setting, and Participants: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. Exposures: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. Main Outcomes and Measures: HIV incidence. Results: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). Conclusions and Relevance: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.

Does Capacity Development Increase Demand for Health Services and Rights Among Key Populations Affected by HIV? A Systematic Review of Evidence from Low and Middle-Income Countries.

Capacity development is a process by which individuals, organizations and societies develop abilities to perform functions, solve problems and achieve objectives. This systematic review sought to document capacity development interventions, the associated outcomes and its effectiveness in increasing demand for rights and health services among key populations (KP) in low and middle-income countries. Twenty papers met our review's selection criteria. Significant improvements in health service utilization were achieved in most community mobilization and peer-led interventions. Whilst we found ample evidence linking capacity development to uptake of services, there was a striking dearth of research examining the impact of capacity development on demand for rights among KP. There was inadequate contextual data to explain variations in intervention effectiveness across different projects. More evidence is needed on the impact of capacity development on demand for health services and rights among KP. Consensus on parameters of capacity development and priority outcomes is required.

Proximate and distant determinants of maternal and neonatal mortality in the postnatal period: A scoping review of data from low- and middle-income countries.

Global maternal and neonatal mortality rates remain unacceptably high. The postnatal period, encompassing the first hour of life until 42 days, is critical for mother-baby dyads, yet postnatal care (PNC) coverage is low. Identifying mother-baby dyads at increased risk for adverse outcomes is critical. Yet few efforts have synthesized research on proximate and distant factors associated with maternal and neonatal mortality during the postnatal period. This scoping review identified proximate and distant factors associated with maternal and neonatal mortality during the postnatal period within low- and middle-income countries (LMICs). A rigorous, systematic search of four electronic databases was undertaken to identify studies published within the last 11 years containing data on risk factors among nationally representative samples. Results were synthesized narratively. Seventy-nine studies were included. Five papers examined maternal mortality, one focused on maternal and neonatal mortality, and the rest focused on neonatal mortality. Regarding proximate factors, maternal age, parity, birth interval, birth order/rank, neonate sex, birth weight, multiple-gestation, previous history of child death, and lack of or inadequate antenatal care visits were associated with increased neonatal mortality risk. Distant factors for neonatal mortality included low levels of parental education, parental employment, rural residence, low household income, solid fuel use, and lack of clean water. This review identified risk factors that could be applied to identify mother-baby dyads with increased mortality risk for targeted PNC. Given risks inherent in pregnancy and childbirth, adverse outcomes can occur among dyads without obvious risk factors; providing timely PNC to all is critical. Efforts to reduce the prevalence of risk factors could improve maternal and newborn outcomes. Few studies exploring maternal mortality risk factors were available; investments in population-based studies to identify factors associated with maternal mortality are needed. Harmonizing categorization of factors (e.g., age, education) is a gap for future research.

On the road to universal coverage of postnatal care: considerations for a targeted postnatal care approach for at-risk mother-baby dyads in low-income and middle-income countries informed by a consultation with global experts.

INTRODUCTION: The potential of timely, quality postnatal care (PNC) to reduce maternal and newborn mortality and to advance progress toward universal health coverage (UHC) is well-documented. Yet, in many low-income and middle-income countries, coverage of PNC remains low. Risk-stratified approaches can maximise limited resources by targeting mother-baby dyads meeting the evidence-based risk criteria which predict poor postnatal outcomes. OBJECTIVES: To review evidence-based risk criteria for identification of at-risk mother-baby dyads, drawn from a literature review, and to identify key considerations for their use in a risk-stratified PNC approach. DESIGN/SETTING/PARTICIPANTS: A virtual, semi-structured group discussion was conducted with maternal and newborn health experts on Zoom. Participants were identified through purposive sampling based on content and context expertise. RESULTS: Seventeen experts, (5 men and 12 women), drawn from policymakers, implementing agencies and academia participated and surfaced several key themes. The identified risk factors are well-known, necessitating accelerated efforts to address underlying drivers of risk. Risk-stratified PNC approaches complement broader UHC efforts by providing an equity lens to identify the most vulnerable mother-baby dyads. However, these should be layered on efforts to strengthen PNC service provision for all mothers and newborns. Risk factors should comprise context-relevant, operationalisable, clinical and non-clinical factors. Even with rising coverage of facility delivery, targeted postnatal home visits still complement facility-based PNC. CONCLUSION: Risk-stratified PNC efforts must be considered within broader health systems strengthening efforts. Implementation research at the country level is needed to understand feasibility and practicality of clinical and non-clinical risk factors and identify unintended consequences.

Pre-exposure prophylaxis rollout in a national public sector program: the Kenyan case study.

Background While advances have been made in HIV prevention and treatment, new HIV infections continue to occur. The introduction of pre-exposure prophylaxis (PrEP) as an additional HIV prevention option for those at high risk of HIV may change the landscape of the HIV epidemic, especially in sub-Saharan Africa, which bears the greatest HIV burden. METHODS: This paper details Kenya's experience of PrEP rollout as a national public sector program. The process of a national rollout of PrEP guidance, partnerships, challenges, lessons learnt and progress related to national scale up of PrEP in Kenya, as of 2018, is described. National rollout of PrEP was strongly lead by the government, and work was executed through a multidisciplinary, multi-organisation dedicated team. This required reviewing available evidence, providing guidance to health providers, integration into existing logistic and health information systems, robust communication and community engagement. Mapping of the response showed that subnational levels had existing infrastructure but required targeted resources to catalyse PrEP provision. Rollout scenarios were developed and adopted, with prioritisation of 19 counties focusing on high incidence area and high potential PrEP users to maximise impact and minimise costs. RESULTS: PrEP is now offered in over 900 facilities countrywide. There are currently over 14000 PrEP users 1 year after launching PrEP. CONCLUSIONS: Kenya becomes the first African country to rollout PrEP as a national program, in the public sector. This case study will provide guidance for low- and middle-income countries planning the rollout of PrEP in response to both generalised and concentrated epidemics.

PrEP for key populations in combination HIV prevention in Nairobi: a mathematical modelling study.

BACKGROUND: The HIV epidemic in the population of Nairobi as a whole is in decline, but a concentrated sub-epidemic persists in key populations. We aimed to identify an optimal portfolio of interventions to reduce HIV incidence for a given budget and to identify the circumstances in which pre-exposure prophylaxis (PrEP) could be used in Nairobi, Kenya. METHODS: A mathematical model was developed to represent HIV transmission in specific key populations (female sex workers, male sex workers, and men who have sex with men [MSM]) and among the wider population of Nairobi. The scale-up of existing interventions (condom promotion, antiretroviral therapy, and male circumcision) for key populations and the wider population as have occurred in Nairobi is represented. The model includes a detailed representation of a PrEP intervention and is calibrated to prevalence and incidence estimates specific to key populations and the wider population. FINDINGS: In the context of a declining epidemic overall but with a large sub-epidemic in MSM and male sex workers, an optimal prevention portfolio for Nairobi should focus on condom promotion for male sex workers and MSM in particular, followed by improved antiretroviral therapy retention, earlier antiretroviral therapy, and male circumcision as the budget allows. PrEP for male sex workers could enter an optimal portfolio at similar levels of spending to when earlier antiretroviral therapy is included; however, PrEP for MSM and female sex workers would be included only at much higher budgets. If PrEP for male sex workers cost as much as US$500, average annual spending on the interventions modelled would need to be less than $3·27 million for PrEP for male sex workers to be excluded from an optimal portfolio. Estimated costs per infection averted when providing PrEP to all female sex workers regardless of their risk of infection, and to high-risk female sex workers only, are $65 160 (95% credible interval [CrI] $43 520-$90 250) and $10 920 (95% CrI $4700-$51 560), respectively. INTERPRETATION: PrEP could be a useful contribution to combination prevention, especially for under-served key populations in Nairobi. An ongoing demonstration project will provide important information regarding practical aspects of implementing PrEP for key populations in this setting. FUNDING: The Bill & Melinda Gates Foundation.

The preexposure prophylaxis revolution; from clinical trials to programmatic implementation.

PURPOSE OF REVIEW: An investment in preexposure prophylaxis (PrEP) delivery must have public health impact in reducing HIV infections. Sustainable delivery of PrEP requires policy, integration of services, and synergy with other existing HIV prevention programs. This review discusses key policy and programmatic considerations for implementation and scale up of PrEP in Africa. RECENT FINDINGS: PrEP delivery has been delayed by concerns about adherence and delivery in 'real world' settings. Demonstration projects and clinical service delivery models are providing evidence of PrEP effectiveness with an impact much higher than that found in randomized clinical trials. Data confirm that PrEP uptake, adherence, and retention has been high, more so by persons who perceive themselves at high risk for HIV infection, and PrEP is well tolerated. PrEP delivery is more than dispensation of a pill and programs should address other risk drivers, which differ by population. In Africa, barriers to PrEP uptake and adherence include stigma among MSM and low HIV risk perception among young women. Additional data have provided insight into optimal points of service delivery, provider training requirements and quality assurance needs. Of the 2 million new HIV infections in 2014, 70% were in Africa. PrEP use is not lifelong, and use limited to periods of risk may be both effective and cost-effective for the continent. SUMMARY: HIV prevention programs should determine strategies to identify those at substantial risk for HIV infection, formulate and deliver PrEP in combination with interventions that target social drivers of HIV vulnerability specific to each population. Policy guidance for optimal combination of interventions and service delivery avenues, clinical protocols, health infrastructure requirements are required. Cost-effectiveness and efficiency data are essential for policy guidance to navigate ethical questions over use of antiretroviral therapy for HIV-negative individuals when treatment coverage has not been attained in many parts of Africa. Countries need to invest in purposeful advocacy at both local and global forums. Failure to implement PrEP will be a failure to protect future generations.

"How I Wish This Thing Was Initiated 100 Years Ago!" Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya.

BACKGROUND: The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. METHODS: Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). RESULTS: 83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. CONCLUSIONS: There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.