President's Emergency Plan For AIDS Relief Research Articles

Who Will Suffer Most if US AIDS Funding Ends.

The President's Emergency Plan for AIDS Relief (PEPFAR) is among the most successful US global health programs. It has moved HIV/AIDS from a certain death to a treatable disease. PEPFAR is now in danger of not being renewed. This perspective seeks to highlight the voice of perinatally HIV-infected Tanzanian youth.

Assessing sex differences in viral load suppression and reported deaths using routinely collected program data from PEPFAR-supported countries in sub-Saharan Africa

BackgroundIn sub-Saharan Africa, more women than men access HIV testing and treatment and may have better viral load suppression (VLS). We utilized routinely reported aggregated HIV program data from 21 sub-Saharan African countries to examine sex differences in VLS and death rates within antiretroviral therapy (ART) programs supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR).MethodsWe included VLS and reported death data for persons aged 15 + years on ART from October–December 2020 disaggregated by sex and age for each subnational unit (SNU). We used linear mixed-model regression to estimate VLS proportion and negative binomial mixed-model regression to estimate the rates of death and death plus interruptions in treatment (IIT). All models were weighted for SNU-level ART population size and adjusted for sex, age, HIV/tuberculosis coinfection, country, and SNU; models for reported deaths and deaths plus IIT were also adjusted for SNU-level VLS.ResultsMean VLS proportion was higher among women than men (93.0% vs. 92.0%, p-value < 0.0001) and 50 + than 15–49 age group (93.7% vs. 91.2%, p-value < 0.0001). The mean rate of reported deaths was higher among men than women (2.37 vs. 1.51 per 1000 persons, p-value < 0.0001) and 50 + than 15–49 age group (2.39 vs. 1.50 per 1000, p-value < 0.0001); the mean rate of reported deaths plus IIT was higher among men (30.1 in men vs. 26.0 in women per 1000, p-value < 0.0001) and higher among 15–49 than 50 + age group (34.7 vs. 22.6 per 1000, p-value < 0.0001).ConclusionsThe mean rate of reported deaths was higher among men in most models despite adjusting for VLS. Further exploration into differences in care-seeking behaviors; coverage of screening, prophylaxis, and/or treatment of opportunistic infections; and more extensive testing options for men to include CD4 is recommended.

Retrospective longitudinal analysis of low-level viremia among HIV-1 infected adults on antiretroviral therapy in Kenya

HIV low-level viremia (LLV) (51-999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes. We calculated rates of virologic suppression (≤50 copies/mL), LLV (51-999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015-2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL) <1000 copies/mL used to predict the next VL). Of 793,902 patients with at least one VL, 18.5% had LLV (51-199 cp/mL 11.1%; 200-399 cp/mL 4.0%; and 400-999 cp/mL 3.4%) and 9.2% had virologic non-suppression at initial result. Among all VLs performed, 26.4% were LLV. Among patients with initial LLV, 13.3% and 2.4% progressed to virologic non-suppression and virologic failure, respectively. Compared to virologic suppression (≤50 copies/mL), LLV was associated with increased risk of virologic non-suppression (adjusted relative risk [aRR] 2.43) and virologic failure (aRR 3.86). Risk of virologic failure increased with LLV range (aRR 2.17 with 51-199 copies/mL, aRR 3.98 with 200-399 copies/mL and aRR 7.99 with 400-999 copies/mL). Compared to patients who never received dolutegravir (DTG), patients who initiated DTG had lower risk of virologic non-suppression (aRR 0.60) and virologic failure (aRR 0.51); similarly, patients who transitioned to DTG had lower risk of virologic non-suppression (aRR 0.58) and virologic failure (aRR 0.35) for the same LLV range. Approximately a quarter of patients experienced LLV and had increased risk of virologic non-suppression and failure. Lowering the threshold to define virologic suppression from <1000 to <50 copies/mL to allow for earlier interventions along with universal uptake of DTG may improve individual and program outcomes and progress towards achieving HIV epidemic control. No specific funding was received for the analysis. HIV program support was provided by the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC).

Estimation of HIV prevalence and burden in Nigeria: a Bayesian predictive modelling study

The cost of population-based surveys is high and obtaining funding for a national population-based survey may take several years, with follow-up surveys taking up to five years. Survey-based prevalence estimates are prone to bias owing to survey non-participation, as not all individuals eligible to participate in a survey may be reached, and some of those who are contacted do not consent to HIV testing. This study describes how Bayesian statistical modeling may be used to estimate HIV prevalence at the state level in a reliable and timely manner. We analysed national HIV testing services (HTS) data for Nigeria from October 1, 2020, to September 30, 2021, to derive state-level HIV seropositivity rates. We used a Bayesian linear model with normal prior distribution and Markov Chain Monte Carlo approach to estimate HIV state-level prevalence for the 36 states+1 FCT in Nigeria. Our outcome variable was the HIV seropositivity rates and we adjusted for demographic, economic, biological, and societal covariates collected from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS), 2018 Nigeria Demographic and Health Survey (NDHS) and 2016-17 Multiple Indicator Cluster Surveys (MICS). The estimated population of 15-49 years olds in each state was multiplied by estimates from the estimated prevalence to generate state-level HIV burden. Our estimated national HIV prevalence was 2.1% (95% CI: 1.5-2.7%) among adults aged 15-49 years in Nigeria, which corresponds to approximately 2 million people living with HIV, compared to previous national HIV prevalence estimates of 1.4% from the 2018 NAIIS and UNAIDS estimation and projection package PLHIV estimation of 1.8 million in 2022. Our modelled HIV prevalence in Nigeria varies by state, with Benue (5.7%, 95% CI: 5.0-6.3) having the highest prevalence, followed by Rivers (5.2%, 95% CI: 4.6-5.8%), Akwa Ibom (3.5%, 95% CI: 2.9-4.1%), Edo (3.4%, 95% CI: 2.9-4.0%) and Taraba (3.0%, 95% CI: 2.6-3.7%) placing fourth and fifth, respectively. Jigawa had the lowest HIV prevalence (0.3%), which was consistent with prior estimates. This model provides a comprehensive and flexible use of evidence to estimate state-level HIV seroprevalence for Nigeria using program data and adjusting for explanatory variables. Thus, investment in program data for HIV surveillance will provide reliable estimates for HIV sub-national monitoring and improve planning and interventions for epidemiologic control. This article was made possible by the support of the American people through the United States Agency for International Development (USAID) under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR).

Population Estimates of HIV Risk Factors to Inform HIV Prevention Programming for Adolescent Girls and Young Women.

Violence Against Children and Youth Survey (VACS) data from seven countries were analyzed to estimate population-level eligibility for the President's Emergency Plan for AIDS Relief (PEPFAR) Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe (DREAMS) HIV prevention program for adolescent girls and young women (AGYW). The prevalence of overall eligibility and individual risk factors, including experiences of violence, social, and behavioral risks differ across countries and age groups. A large proportion of AGYW across all countries and age groups examined have at least one risk factor making them eligible for DREAMS. Experiencing multiple risks is also common, suggesting that researchers and programs could work together to identify combinations of risk factors that put AGYW at greatest risk of HIV acquisition, or that explain most new HIV infections, to more precisely target the most vulnerable AGYW. The VACS provides important data for such analyses to refine DREAMS and other youth programming.

Understanding Gender-Based Violence Service Delivery in CDC-Supported Health Facilities: 15 Sub-Saharan African Countries, 2017-2021.

Gender-based violence (GBV) is a complex issue deeply rooted in social structures, making its eradication challenging. GBV increases the risk of HIV transmission and is a barrier to HIV testing, care, and treatment. Quality clinical services for GBV, which includes the provision of HIV postexposure prophylaxis (PEP), vary, and service delivery data are lacking. We describe GBV clinical service delivery in 15 countries supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Centers for Disease Control and Prevention. Through a descriptive statistical analysis of PEPFAR Monitoring, Evaluation, and Reporting (MER) data, we found a 252% increase in individuals receiving GBV clinical services, from 158,691 in 2017 to 558,251 in 2021. PEP completion was lowest (15%) among 15-19-year-olds. Understanding GBV service delivery is important for policy makers, program managers, and providers to guide interventions to improve the quality of service delivery and contribute to HIV epidemic control.

PEPFAR at 20—Looking Back and Looking Ahead

This Viewpoint looks at PEPFAR (the United States President’s Emergency Plan for AIDS Relief) from its inception to today, including successes and goals for the future to help care for people worldwide living with HIV.

An Evaluation of Local Implementing Partner Performance During the First 2 Years of the USAID/PEPFAR Transition.

Locally led and owned development is considered the best practice for international aid. As an implementing agency for the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the U.S. Agency for International Development (USAID) supported the goal of transitioning 70% of its portfolio funding directly to local organizations by 2020, including partner country governments. However, limited evidence or evaluation exists on how such a transition can help achieve HIV-related health outcomes. We evaluated monitoring, evaluation, and reporting performance; calculated indicators; and quality of service across the HIV/AIDS treatment cascade for local and international partners in the USAID/PEPFAR portfolio implementing similar programs during the U.S. Government fiscal years (FY) 2019 to 2020 (October 1, 2018-September 30, 2020). We compared results aggregated globally, by country, and across individual partners. Globally, local partners met a lower proportion of their treatment targets than international partners and did not meet targets for pre-exposure prophylaxis or voluntary medical male circumcision in FY2020. However, local partners exceeded targets in programs supporting orphans, vulnerable children, and key populations affected by HIV/AIDS. Local partners also had testing positivity, linkage rates, and viral load suppression that were equivalent to or higher than that of international partners. Based on available assessments, local partners displayed quality of service delivery comparable to international partners. Local partners faced challenges, including unfamiliarity with USAID funding, increasing targets across several indicators, and the syndemics of HIV/AIDS and COVID-19. A higher percentage of targets and funding led South African local partners to yield an outsized effect on global percent target achievement. While these findings should be interpreted cautiously due to limited sample size and short time horizon, they are a key first step in evaluating the local partner transition support of the long-term goal of sustained epidemic control of HIV/AIDS.

Geographic prioritisation in Kenya and Uganda: a power analysis of donor transition

Introduction Donor transition for HIV/AIDS programmes remains sensitive, marking a significant shift away from the traditional investment model of large-scale, vertical investments to control the epidemic and achieve rapid scaling-up...

The Status of Adolescent Testing and Treatment in PEPFAR-Supported Programs, October 2017 to September 2020.

Adolescents have poorer outcomes across the HIV cascade compared with adults. We aimed to assess progress in HIV case finding, antiretroviral treatment (ART), viral load coverage (VLC), and viral load suppression (VLS) among adolescents enrolled in the US President's Emergency Plan for AIDS Relief (PEPFAR)-supported programs over a 3-year period that included the beginning of the COVID-19 pandemic. We analyzed PEPFAR program data in 28 countries/regions for adolescents aged 10-19 years between year 1 (October 2017to September 2018), year 2 (October 2018 to September 2019), and year 3 (October 2019 to September 2020). We calculated the number and percent change for HIV tests, HIV-positive tests, and total number on ART. Calculated indicators included positivity, percent of positives newly initiated on ART (ART linkage), VLC (percent of ART patients on ART for ≥6 months with a documented viral load result within the past 12 months), and VLS (percent of viral load tests with <1000 copies/mL). Between years 1 and 3, the number of HIV tests conducted decreased by 44.2%, with a 29.1% decrease in the number of positive tests. Positivity increased from 1.3%-1.6%. The number of adolescents receiving ART increased by 10.4%. In addition, ART linkage increased (77.8%-86.7%) as did VLC (69.4%-79.4%) and VLS (72.8%-81.5%). Our findings demonstrate PEPFAR's success in increasing the adolescent treatment cohort. We identified ongoing gaps in adolescent case finding, linkage, VLC, and VLS that could be addressed with a strategic mix of testing strategies, optimal ART regimens, and adolescent-focused service delivery models.

Vital Signs: Progress Toward Eliminating HIV as a Global Public Health Threat Through Scale-Up of Antiretroviral Therapy and Health System Strengthening Supported by the U.S. President’s Emergency Plan for AIDS Relief — Worldwide, 2004–2022

In 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), with CDC as a major U.S. government implementing agency, began providing HIV antiretroviral therapy (ART) worldwide. Through suppression of HIV viral load, effective ART reduces morbidity and mortality among persons with HIV infection and prevents vertical and sexual transmission. To describe program impact, data were analyzed from all PEPFAR programs and from six countries that have conducted nationally representative Population-based HIV Impact Assessment (PHIA) surveys, including PEPFAR programmatic data on the number of persons with HIV infection receiving PEPFAR-supported ART (2004-2022), rates of viral load coverage (the proportion of eligible persons with HIV infection who received a viral load test) and viral load suppression (proportion of persons who received a viral load test with <1,000 HIV copies per mL of blood) (2015-2022), and population viral load suppression rates in six countries that had two PHIA surveys conducted during 2015-2021. To assess health system strengthening, data on workforce and laboratory systems were analyzed. By September 2022, approximately 20 million persons with HIV infection in 54 countries were receiving PEPFAR-supported ART (62% CDC-supported); this number increased 300-fold from the 66,550 reported in September 2004. During 2015-2022, viral load coverage more than tripled, from 24% to 80%, and viral load suppression increased from 80% to 95%. Despite increases in viral load suppression rates and health system strengthening investments, variability exists in viral load coverage among some subpopulations (children aged <10 years, males, pregnant women, men who have sex with men [MSM], persons in prisons and other closed settings [persons in prisons], and transgender persons) and in viral load suppression among other subpopulations (pregnant and breastfeeding women, persons in prisons, and persons aged <20 years). Since 2004, PEPFAR has scaled up effective ART to approximately 20 million persons with HIV infection in 54 countries. To eliminate HIV as a global public health threat, achievements must be sustained and expanded to reach all subpopulations. CDC and PEPFAR remain committed to tackling HIV while strengthening public health systems and global health security.

Voluntary Medical Male Circumcisions for HIV Prevention — 13 Countries in Eastern and Southern Africa, 2017–2021

In 2007, voluntary medical male circumcision (VMMC) was endorsed by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS after it was found to be associated with approximately a 60% reduction in the risk for female-to-male transmission of HIV (1). As a result of this endorsement, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), through partnerships with U.S. government agencies, including CDC, the U.S. Department of Defense, and the U.S. Agency for International Development, started supporting VMMCs performed in prioritized countries in southern and eastern Africa. During 2010-2016, CDC supported 5,880,372 VMMCs in 12 countries (2,3). During 2017-2021, CDC supported 8,497,297 VMMCs performed in 13 countries. In 2020, the number of VMMCs performed declined 31.8% compared with the number in 2019, primarily because of COVID-19-related disruptions to VMMC service delivery. PEPFAR 2017-2021 Monitoring, Evaluation, and Reporting data were used to provide an update and describe CDC's contribution to the scale-up of the VMMC program, which is important to meeting the 2025 Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 90% of males aged 15-59 years having access to VMMC services in prioritized countries to help end the AIDS epidemic by 2030 (4).

Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa.

The integrase strand transfer inhibitor (INSTI) dolutegravir is recommended in World Health Organization guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy (ART) in Johannesburg, South Africa. We conducted a prospective cohort study of adults (≥16 years) of black African ancestry with HIV who initiated ART between January 2010-December 2020. Patients were propensity score-matched 1:1 (unexposed i.e. remaining on efavirenz: exposed i.e. switched from efavirenz to dolutegravir) on sex, age, months on ART, first ART regimen, haemoglobin, body mass index (BMI), blood pressure, viral load and CD4 count. We used linear regression to assess the effect of switching from efavirenz to dolutegravir on weight change and hypertension 12months after exposure. We matched 794 patients switching to dolutegravir to 794 remaining on efavirenz. Exposed patients had a higher mean change in weight (1.78kg; 95% confidence interval (CI):1.04,2.52kg) from start of follow-up to 12months vs. unexposed. We also found a 14.2 percentage point increase (95% CI: 10.6,17.7) in the risk of hypertension in those exposed to dolutegravir vs those that remained on efavirenz. In a real-world population, patients gained more weight and were at higher risk of hypertension after switching from efavirenz to dolutegravir than those remaining on efavirenz. Longer follow-up is needed, however, to determine if INSTI-associated weight gain is associated with changes in non-communicable disease risk over the long-term, or whether weight gain is sustained, as seen in clinical trials. This study has been made possible by the generous support of the American People and the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID), under the terms of cooperative agreement cooperative Agreement 72067419CA00004. In addition to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1K01MH105320-01A1.

Health Equity in Sickle Cell Research and Access to Therapy

Health Equity in Sickle Cell Research and Access to Therapy

Scale-Up of HIV Antiretroviral Therapy and Estimation of Averted Infections and HIV-Related Deaths - Uganda, 2004-2022.

On January 28, 2003, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the largest commitment by any nation to address a single disease in history, was announced.* In April 2004, the first person in the world to receive PEPFAR-supported antiretroviral therapy (ART) was a man aged 34 years in Uganda. Effective ART reduces morbidity and mortality among persons with HIV infection (1) and prevents both mother-to-child transmission (MTCT) (2) and sexual transmission once viral load is suppressed to undetectable levels (<200 viral copies/mL) (3). By September 2022, more than 1.3 million persons with HIV infection in Uganda were receiving PEPFAR-supported ART, an increase of approximately 5,000% from September 2004. As indicators of the ART program's effectiveness, a proxy MTCT rate decreased 77%, from 6.4% in 2010 to 1.5% in 2022, and the viral load suppression rate (<1,000 viral copies/mL) increased 3%, from 91% in 2016 to 94% in September 2022. During 2004-2022, ART scale-up helped avert nearly 500,000 HIV infections, including more than 230,000 infections among HIV-exposed infants, and approximately 600,000 HIV-related deaths. Going forward, efforts will focus on identifying all persons with HIV infection and rapidly linking them to effective ART. PEPFAR remains committed to continued strong partnership with the Government of Uganda, civil society, and other development partners toward sustainable solutions aligned with the Joint United Nations Programme on HIV/AIDS (UNAIDS) fast-track strategy to ending the global AIDS epidemic by 2030† and safeguarding impact achieved in the long term.

Epidemiology of Tuberculosis Among People Living With HIV in the African Cohort Study From 2013 to 2021.

The prevalence and incidence of tuberculosis (TB) is high among people living with HIV (PLWH) but is often underdiagnosed in HIV programmatic settings. President's Emergency Plan for AIDS Relief (PEPFAR)-supported research sites in Uganda, Kenya, Tanzania, and Nigeria. All patients underwent molecular testing at entry into a longitudinal cohort of PLWH and annually thereafter. We assessed the prevalence and incidence of TB and identified clinical and demographic factors associated with prevalent and incident TB using logistic regression and Cox proportional hazard models. From 21 January, 2013, to 1 December 2021, 3171 PLWH were enrolled with a TB prevalence of 3% (n = 93). Of the cases with prevalent TB, 66% (n = 61) were bacteriologically confirmed. The adjusted odds of prevalent TB were significantly higher among those with higher educational attainment, PLWH for 1-5 years since their HIV diagnosis, those who were underweight, and those with CD4 counts <200 cells/mm 3 . The overall TB incidence rate was 600 per 100,000 person-years (95% CI: 481-748). We found that shorter time since HIV diagnosis, being underweight, taking antiretroviral therapy <6 months, and having a CD4 count <200 cells/mm 3 were significantly associated with incident TB. PLWH on dolutegravir/lamivudine/tenofovir had a 78% lower risk of incident TB compared with those on tenofovir/lamivudine/efavirenz (hazard ratio: 0.22; 95% CI: 0.08-0.63). The prevalence and incidence of TB was notably high in this cohort sourced from PEPFAR clinics. Aggressive efforts to enhance HIV diagnosis and optimize treatment in programmatic settings are warranted to reduce the risk of HIV-TB co-occurrence in this cohort.

Gender-Based Violence Laws in Ten African Countries with High HIV Prevalence and Incidence Among Adolescent Girls and Young Women.

To understand laws pertaining to gender-based violence (GBV) in countries with high HIV prevalence particularly among adolescent girls and young women (AGYW), we reviewed GBV laws and regulations from initial ten eastern and southern African countriesparticipating in the United States President's Emergency Plan for AIDS Relief (PEPFAR) Determined, Resilient, AIDS-free, Mentored, and Safe (DREAMS) Initiative and highlighted similarities and differences across these jurisdictions. All ten countries (Eswatini, Kenya, Lesotho, Malawi, Mozambique, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe) have GBV legislation in place but lack robust information on its implementation and enforcement. Given the known association between GBV and HIV acquisition among AGYW, an increased understanding of GBV laws, their variation across countries and respective gaps, as well as the interplay between enabling, protective, and punitive laws can strengthen policy environments for improved GBV prevention and response, which in turn can lower incidental HIV acquisition among AGYW. For greater impact, GBV policies would require reform, implementation, monitoring, and enforcement.

Pharmacokinetics and efficacy of topical inserts containing tenofovir alafenamide fumarate and elvitegravir administered rectally in macaques.

Topical on-demand forms for HIV pre-exposure prophylaxis (PrEP) may be a desirable alternative for people that prefer not to use daily PrEP. CONRAD has developed inserts containing tenofovir alafenamide (TAF) and elvitegravir (EVG) for on-demand vaginal or rectal pericoital use. We assessed the pharmacokinetics (PK) and pre-exposure efficacy of rectally applied TAF/EVG inserts in macaques. PK was assessed in 12 pigtailed macaques. Tenofovir (TFV) and EVG levels were assayed in rectal biopsies and secretions, and tenofovir-diphosphate (TFV-DP) levels in biopsies and peripheral blood mononuclear cells (PBMC). Drug biodistribution was evaluated in 10 animals at necropsy 4 h post-dosing. For efficacy assessments, one or two TAF/EVG inserts were administered to macaques (n=6) 4 h before repeated rectal SHIV162p3 challenges. One TAF/EVG insert resulted in rapid and high EVG and TFV-DP in rectal tissue 4 h after application. Adding a second insert led to a 10-fold increase in EVG and TFV-DP in rectal tissue. Efficacy of one and two TAF/EVG inserts were 72.6% (CI 24.5%-92.6%) and 93.1% (CI 73.3%-99.2%), respectively. Although high TFV-DP and EVG levels were observed with one rectal TAF/EVG insert, it only conferred partial protection from rectal SHIV challenges. Adding a second insert led to an increase in TFV and EVG in rectal tissues resulting in higher (>90%) efficacy. These results highlight the high efficacy of TAF/EVG inserts as topical on-demand rectal PrEP, as well as the need for appropriate drug coverage in the deep rectum and colon to achieve high protection. The work related to animal studies was funded by CDC intramural funds and an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002). The work related to the insert formulation was funded by U.S. PEPFAR through USAID under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School. The findings and conclusions of this manuscript are those of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC), USAID, President's Emergency Plan for AIDS Relief (PEPFAR), Eastern Virginia Medical School (EVMS), or the US government.

Single dose topical inserts containing tenofovir alafenamide fumarate and elvitegravir provide pre- and post-exposure protection against vaginal SHIV infection in macaques.

Vaginal products for HIV prevention that can be used on-demand before or after sex may be a preferable option for women with low frequency or unplanned sexual activity or who prefer not to use daily or long-acting pre-exposure prophylaxis (PrEP). We performed dose ranging pharmacokinetics (PK) and efficacy studies of a vaginally applied insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) in macaques under PrEP or post-exposure prophylaxis (PEP) modalities. PK studies were performed in 3 groups of pigtailed macaques receiving inserts with different fixed-dose combinations of TAF and EVG (10/8, 20/16 and 40/24mg). PrEP and PEP efficacy of a selected insert was investigated in a repeat exposure vaginal SHIV transmission model. Inserts were administered 4 h before (n=6) or after (n=6) repeated weekly SHIV exposures. Infection outcome was compared with macaques receiving placebo inserts (n=12). Dose ranging studies showed rapid and sustained high drug concentrations in vaginal fluids and tissues across insert formulations with minimal dose proportionality. TAF/EVG (20/16mg) inserts were selected for efficacy evaluation. Five of the 6 animals receiving these inserts 4 h before and 6/6 animals receiving inserts 4 h after SHIV exposure were protected after 13 challenges (p=0.0088 and 0.0077 compared to placebo, respectively). The calculated PrEP and PEP efficacy was 91.0% (95% CI=32.2%-98.8%) and 100% (95% CI=undefined), respectively. Inserts containing TAF/EVG provided high protection against vaginal SHIV infection when administered within a 4 h window before or after SHIV exposure. Our results support the clinical development of TAF/EVG inserts for on-demand PrEP and PEP in women. Funded by CDC intramural funds, an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002), and by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID) under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School.

Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics.

Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics.