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Nationally-representative surveys provide an opportunity to assess trends in recent HIV infection based on assays for recent HIV infection.We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012 and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design.Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 (95% confidence interval [CI] 0.057-0.23), representing 35,900 (95% CI 16,300-55,600) new infections per year in Kenya among persons aged 15-64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 (adjusted odds ratio [aOR]=0.31, p0.001). Compared to no HIV infection, being aged 25-34 versus 35-64 years (aOR=4.2, 95% CI 1.4-13), having more lifetime sex partners (aOR=5.2, 95% CI 1.6-17 for 2-3 partners and aOR=8.6, 95% CI 2.8-26 for ≥4 partners versus 0-1 partners), and never having tested for HIV (aOR=4.1, 95% CI 1.5-11) were independently associated with recent HIV infection.Though HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.

OBJECTIVE We present findings from the nationally representative Zimbabwe Population-based HIV Impact Assessment that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. DESIGN We conducted a cross-sectional household survey. METHODS Consenting adults and children in the household were eligible to participate in Zimbabwe Population-based HIV Impact Assessment (October 2015-August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. Viral load suppression (VLS) was defined as HIV RNA

Between 2010 and 2015, Eswatini conducted mass media health behavior campaigns (HBCs) designed to avert new HIV infections. Using longitudinal data from the nationally representative Swaziland HIV Incidence Measurement Survey of 2011, we describe the impact of exposure to HBCs on selected HIV risk behaviors and HIV incidence among sexually active, HIV-negative adults (n = 11,232). Exposure to partner reduction HBCs was significantly associated with reporting fewer (i.e., 1 versus 2, or 2 versus ≥ 3) sexual partners in the prior 6 months at baseline among women (aOR = 3.02; 95% CI 1.38, 6.62); and at both baseline and at 6-months follow-up for men (aOR = 2.26; 95% CI 1.49, 3.44; aOR = 1.95, 95% CI [1.26-3.00], respectively). Despite these reported partner reductions, there was no association between HBC exposure and prospectively observed HIV seroconversions (n = 121). This analysis strengthens the evidence that HIV prevention at the population level requires integrated strategies.

BACKGROUND HIV population viral load (PVL) can reflect antiretroviral therapy program effectiveness and transmission potential in a community. Using nationally representative data from household surveys conducted in Zimbabwe, Malawi, and Zambia in 2015-16, we examined the association between various VL measures and the probability of at least one recent HIV-1 infection in the community. METHODS We used limiting-antigen avidity enzyme immunoassay, viral load suppression (VLS) (HIV RNA

Background The population-based HIV impact assessment (population-based HIV impact assessments) surveys are among the first to estimate national adult HIV incidence, subnational prevalence of viral load suppression, and pediatric HIV prevalence. We summarize the survey methods implemented in Zimbabwe, Malawi, and Zambia, as well as response rates and quality metrics. Methods Each cross-sectional, household-based survey used a 2-stage cluster design. Survey preparations included sample design, questionnaire development, tablet programming for informed consent and data collection, community mobilization, establishing a network of satellite laboratories, and fieldworker training. Interviewers collected demographic, behavioral, and clinical information using tablets. Blood was collected for home-based HIV testing and counseling (HBTC) and point-of-care CD4+ T-cell enumeration with results immediately returned. HIV-positive blood samples underwent laboratory-based confirmatory testing, HIV incidence testing, RNA polymerase chain reaction (viral load), DNA polymerase chain reaction (early infant diagnosis), and serum antiretroviral drug detection. Data were weighted for survey design, and chi square automatic interaction detection-based methods were used to adjust for nonresponse. Results Each survey recruited a nationally representative, household-based sample of children and adults over a 6-10-month period in 2015 and 2016. Most (84%-90%) of the 12,000-14,000 eligible households in each country participated in the survey, with 77%-81% of eligible adults completing an interview and providing blood for HIV testing. Among eligible children, 59%-73% completed HIV testing. Across the 3 surveys, 97.8% of interview data were complete and had no errors. Conclusion Conducting a national population-based HIV impact assessment with immediate return of HIV and other point-of-care test results was feasible, and data quality was high.

Nationally representative household surveys of the general population can provide critical assessments of the status of HIV epidemics and the impact of national HIV programs. With lessons learned from earlier surveys, PEPFAR has supported HIV-focused surveys in high burden countries to measure known HIV status, access to HIV treatment, and viral suppression, and, by using novel HIV recency assays, to estimate HIV incidence. The results from the initial population-based HIV impact assessments have transformed global HIV programming, demonstrating unexpected progress in population viral suppression and the persistent burden of high HIV incidence among adolescent girls and young women. The findings highlight the importance of tailoring programs to engage men more effectively in HIV testing and treatment. The collection of manuscripts summarized in this overview of the Supplement describe the methods and selected key findings from the initial population-based HIV impact assessment surveys. Taken together, the efforts described in these manuscripts have advanced survey and laboratory capacity and guided HIV programs toward the goal of ending the global epidemic.

A long-acting injectable formulation of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor, is currently under investigation for use in human immunodeficiency virus (HIV) maintenance therapy. We previously characterized RPV metabolism after oral dosing and identified seven metabolites: four metabolites resulting from mono- or dioxygenation of the 2,6-dimethylphenyl ring itself or either of the two methyl groups located on that ring, one N-linked RPV glucuronide conjugate, and two O-linked RPV glucuronides produced via glucuronidation of mono- and dihydroxymethyl metabolites. However, as is true for most drugs, the metabolism of RPV after injection has yet to be reported. The phase II clinical trial HPTN 076 enrolled 136 HIV-uninfected women and investigated the safety and acceptability of long-acting injectable RPV for use in HIV pre-exposure prophylaxis. Through the analysis of plasma samples from 80 of these participants in the active product arm of the study, we were able to detect 2 metabolites after intramuscular injection of long-acting RPV, 2-hydroxymethyl-RPV, and RPV N-glucuronide. Of the total of 80 individuals, 72 participants exhibited detectable levels of 2-hydroxymethyl-RPV in plasma samples whereas RPV N-glucuronide was detectable in plasma samples of 78 participants. In addition, RPV N-glucuronide was detectable in rectal fluid, cervicovaginal fluid, and vaginal tissue. To investigate potential genetic variation in genes encoding enzymes relevant to RPV metabolism, we isolated genomic DNA and performed next-generation sequencing of CYP3A4, CYP3A5, UGT1A1 and UGT1A4. From these analyses, four missense variants were detected for CYP3A4 whereas one missense variant and one frameshift variant were detected for CYP3A5. A total of eight missense variants of UGT1A4 were detected, whereas two variants were detected for UGT1A1; however, these variants did not appear to account for the observed interindividual variability in metabolite levels. These findings provide insight into the metabolism of long-acting RPV and contribute to an overall understanding of metabolism after oral dosing versus injection. ClinicalTrials.gov Identifier: NCT02165202

Background Merely having the tools to end HIV is insufficient. Effectively ending the epidemic necessitates addressing barriers that impede engagement in biomedical and behavioral prevention and wide scale implementation and utilization of existing interventions. This qualitative study identifies suggestions for increasing access to, engagement in, and impact of HIV prevention among women living in cities in high HIV burden counties in the eastern US. Methods Data analyzed for the current study were collected via a qualitative sub-study within the HIV Prevention Trials Network Study 064 (HPTN 064), a multisite observational cohort study designed to estimate HIV incidence among women residing in communities with elevated HIV prevalence who also reported personal or partner characteristics associated with increased risk of HIV acquisition. Focus group and interview participants in the qualitative sub-study (N = 288) were from four cities in the eastern US. Results Thematic analyses revealed four themes describing women’s most frequently stated ideas for improving prevention efforts: 1) Promote Multilevel Empowerment, 2) Create Engaging Program Content, 3) Build “Market Demand”, and 4) Ensure Accessibility. We conducted additional analyses to identify contradictory patterns in the data, which revealed an additional three themes: 1) Address Structural Risk Factors, 2) Increase Engagement via Pleasure Promotion, 3) Expand Awareness of and Access to Prevention Resources. Conclusions Findings may be useful for enhancing women’s engagement in and uptake of behavioral and biomedical HIV prevention resources, improving policy, and addressing multilevel risk factors. Trial registration Clinicaltrials.gov: NCT00995176, prospectively registered.

Between October 2015 and August 2016, Zimbabwe conducted the Zimbabwe Population-Based HIV Impact Assessment (ZIMPHIA) cross-sectional survey to determine progress toward epidemic control. Of 25,131 eligible adults aged 15-64 years, 20,577 (81.8%) consented to face-to-face questionnaire and biomarker testing in this nationally representative household survey. Home-based rapid HIV testing was performed using Determine, First Response, and STAT-PAK as the tiebreaker. HIV-positive tests were confirmed in a laboratory using Geenius HIV-1/2; viral load (VL) was measured using Roche TaqMan and BioMerieux NucliSENS. Recency of infection was tested using Sedia HIV-1 Limiting Antigen (LAg)-Avidity. Presence of antiretroviral (ARV) drugs was detected using high performance liquid chromatography/mass spectrometry (HPLC/MS). The recent infection testing algorithm included LAg-avidity enzyme immunoassay [normalized optical density (ODn ≤1.5), VL ≥1,000 copies/mL, and absence of ARV drugs]. Weighted annual HIV incidence was compared with United Nations Joint Programme on HIV/AIDS (UNAIDS) Spectrum models estimates. Overall, 26 of 2,901 HIV-seropositive individuals had a recent infection (men, 8; women, 18). Overall weighted annual incidence among persons aged 15-64 years was 0.42% [95% confidence interval (CI): 0.25-0.59] and was 0.44% (95% CI: 0.25-0.62) for those aged 15-49 years, similar to 2016 Spectrum model estimate (0.54%, 95% CI: 0.49-0.66) for this age group. Among persons aged 15-49 years, HIV prevalence was 13.35% (95% CI: 12.71-14.02), estimated HIV-positive individuals were 968,951 (95% CI: 911,473-1,026,430), of these, 41,911 (95% CI: 37,412-44,787) were annual-new infections, and this was similar to 2016 Spectrum estimates. The observed HIV incidence in ZIMPHIA 2015-2016 validated the 2016 Spectrum estimates and Zimbabwe's progress toward epidemic control.

Background HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50–60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15–49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence. Methods We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15–49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units. Results We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas. Conclusions Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa.

The narrative is framed within the context of ways that public health interventions balance the rights of individuals and community when related to infectious diseases. This central example is from a community-based HIV testing program in an area with high HIV prevalence. We describe a breach of confidentiality resulting from an involuntary disclosure of a participant’s HIV status. This breach of confidentiality occurs within a family. The narrative considers the respective rights of individuals and community members related to disclosure of HIV status and pays attention to how roles (e.g., health care worker, sexual partner) influence decisions regarding disclosure of someone’s HIV status. There were clear testing program guidelines for how, when, and where to disclose HIV status of household members. Standard operating procedures and careful training were meant to protect data confidentiality and privacy of patients. In practice, things were messier and less clear. The narrative describes how this confidentiality breach occurred, what was done to ensure the participant was safe after the fact and ways to amend the breach on a systems level.

We aimed to measure social protection (SP) coverage among the general population and women and men living with HIV (WLHIV, MLHV), female and male sex workers (FSW, MSW), men who have sex with men (MSM), adolescent girls young women (AGYW), and orphans vulnerable children (OVC). We used Population-Based HIV Impact Assessments data from Eswatini, Malawi, Tanzania and Zambia. We generated survey-weighted proportions for each population group receiving any SP benefits, along with 95% confidence intervals (CI) using jackknife variance estimation. The proportion reported receiving SP benefits among the general population ranged from 7.7% (95% CI: 6.7%:8.8%) in Zambia to 39.6% (95% CI: 36.8%: 42.5%) in Eswatini. SP benefits by WLHIV, MLHIV, AGYW, OVC, SW and MSM were lower than the 2017-19 global average of 45%. Data on access to SP benefits by people living with or affected by HIV from other regions is needed to estimate their SP coverage better. Keywords social protection, cash transfers, people living with HIV, sex workers, adolescent girls and young women, men who have sex with men.

The emergence of new SARS-CoV-2 variants across the world has raised concerns about the effectiveness of available COVID-19 vaccines that were designed against the original Wuhan (wild type) variant. Critical questions have arisen regarding: (a) the effectiveness of various vaccines in preventing infection, symptomatic disease, hospitalization, intensive care unit (ICU) admission and death and (b) the magnitude and clinical consequences of post-vaccination infections in the context of emerging variants, especially the Delta variant of SARS-Cov2. While “real world” experiences with various vaccines have been reported, few have examined comparative effectiveness of various vaccines in one population, as new SARS-CoV-2 variants have emerged. Here we present an analysis of COVID-19 related outcomes from Bahrain, a country with a total population of 1.501 million, where four vaccines were deployed (total vaccinated =1,003,960), including Astra-Zeneca (AZ/Covishield), Pfizer/BioNtech, Sinopharm and Sputnik V. By analyzing individual histories of vaccinated versus unvaccinated cases, we provide a granular description of the effectiveness of the four vaccines, disease burden in unvaccinated versus vaccinated individuals over time, and the risk of four outcomes (infections, hospitalizations, ICU admissions and deaths) due to breakthrough infections among vaccinated individuals. We conclude that the four vaccines were effective in reducing all four outcomes in vaccinated compared to unvaccinated individuals, prior to, and during the period when the Delta variant became dominant in the country (May 2021 to the present). However, after censoring early vaccine recipients of Sinopharm vaccine, compared to Pfizer/BionTech recipients, individuals vaccinated with Sinopharm had a higher risk of post-vaccination infections, hospitalizations, ICU admissions and deaths, especially in those > 50 years old. Our overall findings support the value of vaccination in preventing COVID-19 related events even with the advent of the Delta variant. These data support the urgent need to expand vaccination access around the world, and may serve to guide the choice of vaccines in the context of the Delta variant.

BackgroundAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.ObjectiveTo evaluate the clinical efficacy and safety of convalescent plasma among adults hospitalized with severe and critical COVID-19.DesignRandomized, double-blind, controlled, multicenter, phase 2 trial conducted from April 21st to November 27th, 2020.SettingFive hospitals in New York City (NY, USA) and Rio de Janeiro (Brazil).ParticipantsHospitalized patients aged ≥18 years with laboratory-confirmed COVID-19, infiltrates on chest imaging and oxygen saturation ≤ 94% on room air or requirement for supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.InterventionParticipants were randomized 2:1 to a single transfusion of either 1 unit of convalescent or normal control plasma.MeasurementsThe primary outcome was clinical status at 28 days, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.ResultsOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to normal control plasma. At 28 days, no significant improvement in clinical status was observed in participants randomized to convalescent plasma (with an odds ratio (OR) of a 1-point improvement in the scale: 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180).However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22-0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples (n=40) from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected. Serious adverse events occurred in 39/147 (27%) participants who received convalescent plasma and 26/72 (36%) participants who received control plasma.LimitationsSome participants did not receive high-titer convalescent plasma.ConclusionIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in 28 days clinical status. The significant reduction in mortality associated with convalescent plasma, however, may warrant further evaluation.RegistrationClinicalTrials.gov, NCT04359810FundingAmazon FoundationClinical Trial RegistrationClinicalTrials.gov Identifier: NCT04359810

Reducing HIV-related morbidity and mortality, and effectively eliminating HIV transmission risk, depends on use of antiretroviral therapy (ART) to achieve and maintain viral load suppression (VLS)* (1,2). By 2020, sub-Saharan African countries are working to achieve VLS among 90% of persons using ART and 73% of all persons living with HIV infection (1). In Tanzania, a country with 1.4 million persons with HIV infection, 49.6% of HIV-positive persons aged 15-49 years had achieved VLS in 2017, including only 21.5% of men and 44.6% of women aged 25-29 years (3). To identify interventions that might increase VLS in Tanzania, and reduce VLS-associated sex and age-group disparities, the Bukoba Combination Prevention Evaluation (BCPE) scaled up new HIV testing, linkage to care, and retention on ART interventions throughout Bukoba Municipal Council (Bukoba), Tanzania, during October 2014-March 2017 (4,5). Located on the western shore of Lake Victoria, Bukoba is a mixed urban and rural municipality of 150,000 persons and capital of Kagera Region. Of the 31 regions of Tanzania, Kagera has the fourth highest prevalence of HIV infection (6.8%) among residents aged 15-49 years (3). CDC analyzed data from BCPE preintervention and postintervention surveys and found that VLS prevalence among HIV-positive Bukoba residents aged 18-49 years increased approximately twofold overall (from 28.6% to 64.8%) and among women (33.3% to 67.8%) and approximately threefold among men (20.5% to 59.1%) and young adults aged 18-29 years (15.6% to 56.7%). During 2017, BCPE facility-based testing and linkage interventions were approved as new service delivery models by the Tanzania Ministry of Health, Community Development, Gender, Elderly and Children (4,5). After a successful rollout to 208 facilities in 11 regions in 2018, BCPE interventions are being scaled up in all regions of Tanzania in 2019 with support from the United States President's Emergency Plan for AIDS Relief (PEPFAR).†.

Summary Background Observational and laboratory studies suggest that some hormonal contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM), might increase women's susceptibility to HIV acquisition. We aimed to compare DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant among African women seeking effective contraception and living in areas of high HIV incidence. Methods We did a randomised, multicentre, open-label trial across 12 research sites in eSwatini, Kenya, South Africa, and Zambia. We included HIV-seronegative women aged 16–35 years who were seeking effective contraception, had no medical contraindications to the trial contraceptive methods, agreed to use the assigned method for 18 months, and reported not using injectable, intrauterine, or implantable contraception for the previous 6 months. Participants were randomly assigned (1:1:1) to receive an injection of 150 mg/mL DMPA-IM every 3 months, a copper IUD, or a LNG implant with random block sizes between 15 and 30, stratified by site. Participants were assigned using an online randomisation system, which was accessed for each randomisation by study staff at each site. The primary endpoint was incident HIV infection in the modified intention-to-treat population, including all randomised participants who were HIV negative at enrolment and who contributed at least one HIV test. The primary safety endpoint was any serious adverse event or any adverse event resulting in method discontinuation, until the trial exit visit at 18 months and was assessed in all enrolled and randomly assigned women. This study is registered with ClinicalTrials.gov, number NCT02550067. Findings Between Dec 14, 2015, and Sept 12, 2017, 7830 women were enrolled and 7829 were randomly assigned to the DMPA-IM group (n=2609), the copper IUD group (n=2607), or the LNG implant group (n=2613). 7715 (99%) participants were included in the modified intention-to-treat population (2556 in the DMPA-IM group, 2571 in the copper IUD group, and 2588 in the LNG implant group), and women used their assigned method for 9567 (92%) of 10 409 woman-years of follow-up time. 397 HIV infections occurred (incidence 3·81 per 100 woman-years [95% CI 3·45–4·21]): 143 (36%; 4·19 per 100 woman-years [3·54–4·94]) in the DMPA-IM group, 138 (35%: 3·94 per 100 woman-years [3·31–4·66]) in the copper IUD group, and 116 (29%; 3·31 per 100 woman-years [2·74–3·98]) in the LNG implant group. In the modified intention-to-treat analysis, the hazard ratios for HIV acquisition were 1·04 (96% CI 0·82–1·33, p=0·72) for DMPA-IM compared with copper IUD, 1·23 (0·95–1·59, p=0·097) for DMPA-IM compared with LNG implant, and 1·18 (0·91–1·53, p=0·19) for copper IUD compared with LNG implant. 12 women died during the study: six in the DMPA-IM group, five in the copper IUD group, and one in the LNG implant group. Serious adverse events occurred in 49 (2%) of 2609 participants in the DMPA-IM group, 92 (4%) of 2607 participants in the copper IUD group, and 78 (3%) of 2613 participants in the LNG implant group. Adverse events resulting in discontinuation of the randomly assigned method occurred in 109 (4%) women in the DMPA-IM group, 218 (8%) women in the copper IUD group, and 226 (9%) women in the LNG implant group (p Interpretation We did not find a substantial difference in HIV risk among the methods evaluated, and all methods were safe and highly effective. HIV incidence was high in this population of women seeking pregnancy prevention, emphasising the need for integration of HIV prevention within contraceptive services for African women. These results support continued and increased access to these three contraceptive methods. Funding Bill & Melinda Gates Foundation, US Agency for International Development and the President's Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council, and UN Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.

HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15–49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa., Fine-scale estimates of the prevalence of HIV in adults across sub-Saharan Africa reveal substantial within-country variation and local differences in both the direction and rate of change in the prevalence of HIV between 2000 and 2017.

With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA

An amendment to this paper has been published and can be accessed via the original article.

Summary Background As oral pre-exposure prophylaxis (PrEP) becomes the standard of prevention globally, its potential effect on HIV incidence in clinical trials of new prevention interventions is unknown, particularly for trials among women. In a trial measuring HIV incidence in African women, oral PrEP was incorporated into the standard of prevention in the trial's last year. We assessed the effect of on-site access to PrEP on HIV incidence in this natural experiment. Methods We did a nested interrupted time-series study using data from the ECHO trial. At 12 sites in four countries (Eswatini, Kenya, South Africa, and Zambia), women (aged 16–35 years) were randomly assigned to receive one of three contraceptives between Dec 14, 2015, and Sept 12, 2017, and followed up quarterly for up to 18 months to determine the effect of contraceptive method on HIV acquisition. Women were eligible if they wanted long-acting contraception, were medically qualified to receive study contraceptives, and had not used any of the study contraceptives in the past 6 months. The present analyses are limited to nine South African sites where on-site access to oral PrEP was implemented between March 13 and June 12, 2018. Using an interrupted time-series design, we compared HIV incidence before versus after PrEP access, limited to quarterly study visits at which on-site PrEP access was available to at least some participants and, in a sensitivity analysis, to the 180 days before and after access. The outcome was incident HIV infection, detected using two rapid HIV tests done in parallel for each participant at every scheduled follow-up visit. This study is registered on ClinicalTrials.gov, NCT02550067. Findings 2124 women were followed up after on-site PrEP access began, of whom 543 (26%) reported PrEP use. A total of 12 HIV seroconversions were observed in 556 person-years (incidence 2·16%) after on-site PrEP access, compared with 133 HIV seroconversions in 2860 person-years (4·65%) before PrEP access (adjusted incidence rate ratio [IRR] 0·45, 95% CI 0·25–0·82, p=0·0085). Similar results were also observed when limiting the analysis to 180 days before versus after PrEP access. A total of 46 HIV seroconversions were observed in 919 person-years within 180 days before PrEP access, compared with 11 seroconversions in 481 person-years in the 180 days following PrEP access (incidence 5·00 vs 2·29 per 100 person-years; IRR 0·43, 95% CI 0·22–0·88, p=0·012). Interpretation On-site access to PrEP as part of standard of prevention in a clinical trial among women in South Africa was associated with halving HIV incidence, when approximately a quarter of women started PrEP. Providing access to on-site PrEP could decrease incidence in HIV prevention trials. These data are also among the first to show in any setting that access to PrEP is associated with decreased HIV acquisition among South African women. Funding Bill & Melinda Gates Foundation, United States Agency for International Development, President's Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency, South African Medical Research Council, and United Nations Population Fund.

Summary Background Community randomised trials have had mixed success in implementing combination prevention strategies that diagnose 90% of people living with HIV, initiate and retain on antiretroviral therapy (ART) 90% of those diagnosed, and achieve viral load suppression in 90% of those on ART (90-90-90). The Bukoba Combination Prevention Evaluation (BCPE) aimed to achieve 90-90-90 in Bukoba Municipal Council, Tanzania, by scaling up new HIV testing, linkage, and retention interventions. Method We did population-based, cross-sectional surveys before and after our community-wide intervention in Bukoba—a mixed urban and rural council of approximately 150 000 residents located on the western shore of Lake Victoria in Tanzania. BCPE interventions were implemented in 11 government-supported health-care facilities throughout Bukoba from Oct 1, 2014, to March 31, 2017, when national ART-eligibility guidelines expanded from CD4 counts of less than 350 cells per μL (Oct 1, 2014–Dec 31, 2015) and 500 or less cells per μL (Jan 1, 2016–Sept 30, 2016) to any CD4 cell count (test and treat, Oct 1, 2016–March 31, 2017). We used pre-intervention (Nov 4, 2013–Jan 25, 2014) and post-intervention (June 21, 2017–Sept 20, 2017) population-based household surveys to assess population prevalence of undiagnosed HIV infection and ART coverage, and progress towards 90-90-90, among residents aged 18–49 years. Findings During the 2·5-year intervention, BCPE did 133 695 HIV tests, diagnosed and linked 3918 people living with HIV to HIV care at 11 Bukoba facilities, and returned to HIV care 604 patients who had stopped care. 4795 and 5067 residents aged 18–49 years participated in pre-intervention and post-intervention surveys. HIV prevalence before and after the intervention was similar: pre-intervention 8·9% (95% CI 7·5–10·4); post-intervention 8·4% (6·9–9·9). Prevalence of undiagnosed HIV infection decreased from 4·7% to 2·0% (prevalence ratio 0·42, 95% CI 0·31–0·57), and current ART use among all people living with HIV increased from 32·2% to 70·9% (2·20, 1·82–2·66) overall, 23·0% to 62·1% among men (2·70, 1·84–3·96), and 16·7% to 64·4% among people aged 18–29 years (3·87, 2·54–5·89). Of 436 and 435 people living with HIV aged 18–49 years who participated in pre-intervention and post-intervention surveys, previous HIV diagnosis increased from 47·4% (41·3–53·4) to 76·2% (71·8–80·6), ART use among diagnosed people living with HIV increased from 68·0% (60·9–75·2) to 93·1% (90·2–96·0), and viral load suppression of those on ART increased from 88·7% (83·6–93·8) to 91·3% (88·6–94·1). Interpretation BCPE findings suggest scaling up recommended HIV testing, linkage, and retention interventions can help reduce prevalence of undiagnosed HIV infection, increase ART use among all people living with HIV, and make substantial progress towards achieving 90-90-90 in a relatively short period. BCPE facility-based testing and linkage interventions are undergoing national scale up to help achieve 90-90-90 in Tanzania. Funding US Presidents' Emergency Plan for AIDS Relief.

Africa in the Path of Covid-19 Despite intensive preparations by African countries that are no strangers to epidemics, we should have no illusions that Africa can confront the Covid-19 threat alone...

Background: Daily oral TDF/FTC is protective against HIV infection when used for pre-exposure prophylaxis (PrEP). However, daily adherence to oral PrEP is difficult for many; therefore, finding alternative PrEP strategies remains a priority. HPTN 076 evaluated the long-acting injectable form of rilpivirine (RPV), known as RPV LA for safety, pharmacokinetics and acceptability. Methods: HPTN 076 (NTC 02165202) was a phase 2, double-blind, 2:1 randomized trial comparing the safety of 1200mg RPV LA (LA) to placebo (P). The study included a 28-day oral run-in phase of daily, self- administered oral RPV (25 mg), with directly observed oral dosing about six times. Of 136 enrolled sexually active, HIV-uninfected, low HIV-risk African (100) and US (36) adult women, injectable product was administered in two gluteal, intramuscular (IM) injections once every eight weeks to 122 participants following the oral run-in phase. A maximum of six injection time points occurred over a 48-week period. Acceptability, safety, tolerability and pharmacokinetic (PK) data were collected throughout the study. This paper includes primary endpoint data collected up to the week 52 post enrollment. Findings: The median age of the enrolled population was 31 years (IQR: 25,38), median weight 75 kg (IQR: 64, 89), median body mass index (BMI) 30 (IQR: 27, 35), 46% married, 94% Black and 60% unemployed. A total of 122 (80 LA, 42 P) women received at least one injection and 98 (64 LA, 34 P) received all six injections. During the injection phase, three women withdrew from the study (2 LA, 1 P) and 16 women discontinued study product (10 LA, 6 P). Fourteen women (11 LA and 3 P) discontinued oral study product and did not enter the injection phase. Study product discontinuations were not significantly different between the two arms throughout. Of the product discontinuations in the injection phase, 8% in LA and 5% in P arm were due to adverse events (AEs), including one randomized to the P arm with prolonged QTc interval on EKG. The proportion of women who experienced Grade 2 or higher AEs during the injection phase as the primary outcome was not significantly different between the two arms [73.8%, 95% CI: (63.2%, 82.1%) for LA and 73.8%, 95% CI: (58.9%, 84.7%), p>0.99]. Transient Grade ≥2 liver abnormalities occurred in 14% of women in the LA arm compared with 12% in P arm. Three LA women (4%) developed Grade 3 injection site reactions compared with none in P arm. In participants who received at least 1 injection, the geometric mean of overall RPV trough concentrations (Ctrough) was 62.2 ng/mL. In participants who received all six injections, the geometric mean of CTrough through the injection phase and after the last injection were 72.8 ng/mL and 100.9 ng/mL, respectively. At week 52 (eight weeks after last injection), the geometric mean of RPV Ctrough was 75.0 ng/mL. At the last injection visit (Week 44), 80 % of women who answered acceptability questions strongly agreed that they would think about using- and 68% that they would definitely use a PrEP injectable in the future. Interpretation: RPV LA IM injections every eight weeks in African and US women were safe and acceptable. Overall, despite more injection site reactions and pain in the participants receiving RPV LA the injections were well tolerated. Data from this study support the further development of injectable PrEP agents. Keyword: RPV LA as Pre exposure prophylaxis

Objectives The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. Trial Design This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. Participants Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. Intervention and comparator The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 – 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 – 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. Main outcomes The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. Randomization Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. Blinding (masking) The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. Numbers to be randomized (sample size) We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. Trial Status Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. Trial registration ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

OBJECTIVE: The Lesotho Population-based HIV Impact Assessment survey was conducted nationally and designed to measure HIV prevalence, incidence, and viral load suppression (VLS). DESIGN: A nationally representative sample of 9403 eligible households was surveyed between November 2016 and May 2017; analyses account for study design. Consenting participants provided blood samples, socio-demographic, and behavioral information. METHODS: Blood samples were tested using the national rapid HIV testing algorithm. HIV-seropositive results were confirmed with Geenius supplemental assay. Screening for detectable concentrations of antiretroviral analytes was conducted on dried blood specimens from all HIV-positive adults using high-resolution liquid chromatography coupled with tandem mass spectrometry. Self-reported and/or antiretroviral biomarker data were used to classify individuals as HIV-positive and on treatment. Viral load testing was performed on all HIV-positive samples at central labs. VLS was defined as HIV RNA below 1000 copies/ml. RESULTS: Overall, 25.6% of adults aged 15–59 years were HIV-positive. Among seropositive adults, 81.0% (male 76.6%, female 84.0%) reported knowing their HIV status, 91.8% of people living with HIV (male 91.6%, female 92.0%) who reported knowing their status reporting taking antiretrovirals, and 87.7% (male and female 87.7%) of these had VLS. Younger age was significantly associated with being less likely to be aware of HIV status for both sexes. CONCLUSIONS: Findings from this population-based survey provide encouraging data in terms of HIV testing and treatment uptake and coverage. Specific attention to reaching youth to engage them in HIV-related interventions are critical to achieving epidemic control.

HIV Population Surveys The Population-based HIV Impact Assessment Project now has initial findings available from surveys in seven sub-Saharan African countries. The findings reveal both exceptional successes and common ongoing challenges in addressing heavy HIV burdens.

Reliable and accurate laboratory assays to detect recent HIV-1 infection have potential as simple and practical methods of estimating HIV-1 incidence in cross-sectional surveys. This study describes validation of the limiting-antigen (LAg) avidity enzyme immunoassay (EIA) in a cross-sectional national survey, conducted in Swaziland, comparing it to prospective follow-up incidence. As part of the Swaziland HIV-1 Incidence Measurement Survey (SHIMS), 18,172 individuals underwent counseling and HIV rapid testing in a household-based, population survey conducted from December 2010 to June 2011. Plasma samples from HIV-positive persons were classified as recent infections using an incidence testing algorithm with LAg-Avidity EIA (normalized optical density ≤1.5) followed by viral load (VL ≥1,000 copies/mL). All HIV-seronegative samples were tested for acute HIV-1 infection by nucleic acid amplification test (NAAT) pooling. HIV-seronegative individuals who consented to follow-up were retested ∼6 months later to detect observed HIV-1 seroconversion. HIV-1 incidence estimates based on LAg+VL and NAAT were calculated using assay-specific parameters and were compared with prospective incidence estimate. A total of 5,803 (31.9%) of 18,172 survey participants tested HIV seropositive; of these 5,683 (97.9%) were further tested with LAg+VL algorithm. The weighted annualized incidence from the longitudinal cohort study was 2.4% (95% confidence interval 2.0-2.7). Based on cross-sectional testing of HIV positives with LAg+VL algorithm, overall weighted annualized HIV-1 incidence was 2.5% (2.0-3.0), whereas NAAT-based incidence was of 2.6%. In addition, LAg-based incidence in men (1.8%; 1.2-2.5) and women (3.2%; 2.4-3.9) were similar to estimates based on observed incidence (men = 1.7%, women = 3.1%). Changes in HIV-1 incidence with age in men and women further validate plausibility of the algorithm. These results demonstrate that the LAg EIA, in a serial algorithm with VL, is a cost-effective tool to estimate HIV-1 incidence in cross-sectional surveys.

Background: In Tanzania, a country with 1.4 million persons living with HIV (PLHIV), information is needed on services that can help diagnose 90% of PLHIV, initiate and retain on antiretroviral therapy (ART) 90% of those diagnosed, and achieve viral load suppression (VLS) among 90% of those on ART (90-90-90). The Bukoba Combination Prevention Evaluation (BCPE) aimed to achieve 90-90-90 in Bukoba Municipal Council (Bukoba) by scaling up new HIV testing, linkage to care, and ART retention interventions. Method: Located on the western shore of Lake Victoria, Bukoba is a mixed urban and rural council of approximately 150,000 residents. BCPE interventions were implemented throughout Bukoba during October 2014 — March 2017 when national ART-eligibility guidelines expanded from CD4

Data suggest that pregnant women in some settings have high prevalence of HIV and other sexually transmitted infections (STI). We examined changes in sexual risk behaviors and intravaginal practices during pregnancy that may contribute to HIV and STI incidence using data from the Methods for Improved Reproductive Health in Africa study conducted in South Africa and Zimbabwe 2003–2006. We used a crossover design and modified Poisson regression to compare behaviors among HIV negative women 18–45 years during pregnant and non-pregnant periods. Among the 4802 women