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Mobile women are at risk of HIV infection in sub-Saharan Africa, although we lack evidence for HIV risk among women in mobile partnerships, especially in the context of household food insecurity, a growing concern in the region.Women aged 15-59 years with a cohabitating male partner who participated in population-based HIV impact assessment surveys in Eswatini, Lesotho, Namibia, Tanzania, Uganda, and Zambia.We evaluated the association between women's and their partner's mobility (being away from home for more than 1 month or staying elsewhere) and transactional sex (selling sex or receiving money or goods in exchange for sex). We examined associations for effect measure modification by food insecurity level in the household in the past month. We used survey-weighted logistic regression, pooled and by country, adjusting for individual, partner, and household-level variables.Among women with a cohabitating male partner, 8.0% reported transactional sex, ranging from 2.7% in Lesotho to 13.4% in Uganda. Women's mobility [aOR 1.35 (95% CI: 1.08 to 1.68)], but not their partner's mobility [aOR 0.91 (0.74-1.12)], was associated with transactional sex. Food insecurity was associated with transactional sex independent of mobility [aOR 1.29 (1.10-1.52)]. Among those who were food insecure, mobility was not associated with increased odds of transactional sex.Food insecurity and women's mobility each increased the odds of transactional sex. Because transactional sex is associated with HIV risk, prevention programs can address the needs of mobile and food-insecure women, including those in cohabitating relationships.

Background Adolescents aged 10–19 years living with human immunodeficiency virus (HIV) (ALHIV), both perinatally infected adolescents (APHIV) and behaviorally infected adolescents (ABHIV), are a growing population with distinct care needs. We characterized the epidemiology of HIV in adolescents included in Population-based HIV Impact Assessments (2015–2017) in Zimbabwe, Malawi, Zambia, Eswatini, and Lesotho. Methods Adolescents were tested for HIV using national rapid testing algorithms. Viral load (VL) suppression (VLS) was defined as VL, Based on national surveys, fewer than half of adolescents living with human immunodeficiency virus (HIV) in 5 countries in southern Africa were virally suppressed, and 68.7% classified as perinatally infected had undiagnosed HIV or HIV diagnosed at age ≥10 years.

Supplemental Digital Content is Available in the Text., Background: HIV-1 risk scoring tools could help target provision of prevention modalities such as pre-exposure prophylaxis. Recent research suggests that risk scores for women aged 18–45 may not predict risk well among young women aged 18–24. We evaluated the predictive performance of age-specific risk scores compared with the existing non–age-specific VOICE risk score, developed for women aged 18–45. Methods: We conducted a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes Trial to develop and internally validate HIV-1 risk scores for women aged 18–24 and 25–35 in South Africa. Candidate predictors included baseline demographic, clinical, behavioral, and contextual characteristics readily available in clinical settings. The VOICE risk score was applied to women aged 18–35. We evaluated predictive performance of each risk score by area under the receiver operating characteristic curve (AUC). Results: Predictive performance of all risk scores was moderate, with AUC (95% confidence interval) of 0.64 (0.60 to 0.67) among women aged 18–24, 0.68 (0.62 to 0.73) among those aged 25–35, and 0.61 (0.58 to 0.65) for the VOICE risk score applied to women aged 18–35; The AUC was similar in internal validation. Among women aged 18–24, HIV-1 incidence was high even at low risk scores, at 3.9 per 100 person-years (95% confidence interval: 3.2 to 4.7). Conclusions: All risk scores were moderately predictive of HIV-1 acquisition, and age-specific risk scores performed only marginally better than the VOICE non–age-specific risk score. Approaches for targeted pre-exposure prophylaxis provision to women in South Africa may require more extensive data than are currently available to improve prediction.

IntroductionFood insecurity has a bidirectional relationship with HIV infection, with hunger driving compensatory risk behaviors, while infection can increase poverty. We used a laboratory recency assay to estimate the timing of HIV infection vis-à-vis the timing of severe food insecurity (SFI).MethodsData from population-based surveys in Zambia, Eswatini, Lesotho, Uganda, and Tanzania and Namibia were used. We defined SFI as having no food ≥three times in the past month. Recent HIV infection was identified using the HIV-1 LAg avidity assay, with a viral load (>1000 copies/ml) and no detectable antiretrovirals indicating an infection in the past 6 months. Logistic regression was conducted to assess correlates of SFI. Poisson regression was conducted on pooled data, adjusted by country to determine the association of SFI with recent HIV infection and risk behaviors, with effect heterogeneity evaluated for each country. All analyses were done using weighted data.ResultsOf 112,955 participants aged 15-59, 10.3% lived in households reporting SFI. SFI was most common in urban, woman-headed households. Among women and not men, SFI was associated with a two-fold increase in risk of recent HIV infection (adjusted relative risk [aRR] 2.08, 95% CI 1.09-3.97), with lower risk in high prevalence countries (Eswatini and Lesotho). SFI was associated with transactional sex (aRR 1.28, 95% CI 1.17-1.41), a history of forced sex (aRR 1.36, 95% CI 1.11-1.66), and condom-less sex with a partner of unknown or positive HIV status (aRR 1.08, 95% CI 1.02-1.14) in all women, and intergenerational sex (partner ≥10 years older) in women aged 15-24 (aRR 1.23, 95% CI 1.03-1.46), although this was heterogeneous. Recent receipt of food support was protective (aRR 0.36, 95% CI 0.14-0.88).ConclusionSFI increased risk for HIV acquisition in women by two-fold. Worsening food scarcity due to climactic extremes could imperil HIV epidemic control.SUMMARYWhat is already knownThe link between food insecurity and the adoption of high-risk sexual behaviors as a coping mechanism has been shown in several settings.HIV infection can also drive food insecurity due to debilitating illness reducing productivity, the costs of treatment diverting money from supplies, and potentially reduced labor migration.Food insecurity has been associated with chronic HIV infection, but it has not been linked with HIV acquisition.What are the new findingsThis study of 112,955 adults across six countries in sub-Saharan Africa provides unique information on the association between acute food insecurity and recent HIV infection in women, as well as the potential behavioral and biological mediators, including community viremia as a measure of infectiousness.The data enabled a comprehensive analysis of factors associated with risk of infection, and how these factors differed by country and gender. Women living in food insecure households had a two-fold higher risk of recent HIV acquisition, and reported higher rates of transactional sex, early sexual debut, forced sex, intergenerational sex and sex without a condom with someone of unknown or positive HIV status. This pattern was not seen in men.This study is also the first to demonstrate a protective association for food support, which was associated with a lower risk of recent HIV infection in women.What do the new findings implyIn light of worsening food insecurity due to climate change and the recent COVID-19 pandemic, our results support further exploration of gender-specific pathways of response to acute food insecurity, particularly how women’s changes in sexual behavior heighten their risk of HIV acquisition.These and other data support the inclusion of food insecurity in HIV risk assessments for women, as well as the exploration of provision of food support to those households at highest risk based on geographic and individual factors.

Prior HIV testing and awareness of HIV-positive status were assessed among HIV-positive adults at 20 clinics in Eswatini. Of 2196 HIV-positive adults, 1183 (53.8%) reported no prior HIV testing, and 1948 (88.7%) were unaware of their HIV-positive status. Males [adjusted odds ratio, AOR, (95% confidence interval): 0.7 (0.5–0.9)], youth 18–25 years [AOR 0.6 (0.4–0.95)], adults ≥ 50 years [AOR 0.5 (0.3–0.9)], those needing family support [AOR 0.6 (0.5–0.8)], and those living ≥ 45 min from clinic [AOR 0.5 (0.4–0.8)] were less likely to know their HIV-positive status. More HIV testing is needed to achieve 95-95-95 targets, with targeted strategies for those less likely to test for HIV.

Globally, women have higher herpes simplex virus type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM).Within a randomized trial of the effect of 3 contraceptive methods-DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant-on human immunodeficiency virus (HIV) acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015 to 2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method.At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI], .65-.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI, .71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI, .89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55; 95% CI, 2.78-4.48).In a randomized trial, we found no association between HSV-2 acquisition and use of 3 contraceptive methods.ClinicalTrials.gov number NCT02550067.

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

BACKGROUND High response rates in surveys are critical to ensuring that findings are unbiased and representative of the target population. Questionnaire length affects response rates, with long interviews associated with partially complete surveys, higher item nonresponse ("don't know" and "refuse" responses), and willingness to participate in future surveys. Our aim is to determine the impact of questionnaire length on blood test participation in population-based HIV surveys. METHODS Data are from population-based HIV impact assessments conducted in Zambia, Eswatini, and Lesotho in 2016-2017. The population-based HIV impact assessments consist of an interview followed by a blood draw. Consent for blood draw was obtained before the interview in Eswatini and after the interview in Zambia and Lesotho. Interview length was measured by the survey tablet as the time to complete the survey (interview duration) and the number of questions answered by the participant (questionnaire length). We assessed the effects of questionnaire length and interview duration on blood test participation using logistic regression. RESULTS Across all 3 surveys, the median interview duration was 16 minutes and the median number of questions was 77. In adjusted analyses, there was a negative impact of interview duration on blood draw consent for individuals with unknown status in Lesotho and a positive relationship between questionnaire length and blood draw consent in Zambia for those with HIV-negative and unknown status. CONCLUSION Although interview length is an important consideration to reduce respondent burden, a longer questionnaire does not necessarily result in lower consent rates for blood testing.

Background: Conflicting evidence obscures the role of partnerships with older men in the HIV epidemic in adolescent girls and young women (AGYW, aged 15-24) in sub-Saharan Africa. We assessed the effect of partner age and potential mediators on AGYW HIV infection using data from Population-based HIV Impact Assessments in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe. Methods: PHIA surveys collect data on HIV-related outcomes. Recent infection was estimated using an HIV-1 LAg avidity assay algorithm. We examined the association between reported partner age and recent AGYW HIV infection, incorporating population-level HIV prevalence and viremia from the reported male age-band. Logistic regression analyses compared the odds of recent infection in AGYW with older male partners to those reporting same-age male partner, adjusting for AGYW age, country, and urban/rural residence. Dyadic analysis examined observed cohabitating partner age, HIV status, and viremia to assess associations with recent and prevalent infection in their AGYW spouses. Findings: Among 17,813 AGYW, increasing reported partner age was associated with higher odds of recent infection, with the highest odds for partners aged 35-44 years (adjusted odds ratio (aOR) 8·94, 95% CI 2·63-30·37) compared to partners aged 15-24. Population-level viremia was highest in this male age-band. Dyadic analyses of 5,432 partnerships confirmed the association between partner age-band of 35-44 and prevalent HIV infection (aOR 3·82, 95% CI 2·17-6·75). However, most new infections were in AGYW with partners aged 25-34, as the majority of AGYW had partners in this age-band. Interpretation: These results provide evidence that men aged 25-34 drive most AGYW infections, but partners over 9 years older than AGYW in the 35-44 age-band confer greater risk. Population-level infectiousness and male age should be incorporated into identifying high-risk typologies. Funding Information: This research publication has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the US Centers for Disease Control and Prevention (CDC) under the terms of cooperative agreements U2GGH001226 and U2GGH001271. Joanne Mantell and Susie Hoffman were supported by a NIMH Center Grant P30-MH43520 (Principal Investigator: Robert H. Remien, PhD). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies. Declaration of Interests: Authors declare that they have no competing interests. Ethics Approval Statement: A guardian or parent provided permission for interviewers to approach 10-17-year-olds who then assented. Informed consent/assent was documented via electronic signature, with witnesses verifying consent for illiterate individuals The PHIA protocols were approved by national ethics committees, and the institutional review boards at Columbia University Irving Medical Center, the University of California in San Francisco for Namibia, and the US Centers for Disease Control and Prevention.

Background: Globally, women have higher herpes simplex type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of certain contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM). Methods: Within a randomized trial of the effect of three contraceptive methods – DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant – on HIV acquisition, we assessed HSV-2 acquisition. We followed women who were HSV-2 and HIV seronegative, aged 16-35 years, and seeking effective contraception for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015-2018. HSV-2 serologic testing was done at enrollment and final study visits according to a standardized algorithm. Intention–to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. Findings: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI] 0.65-0.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI 0.71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI 0.89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55, 95% CI 2.78-4.48). Interpretation: In a randomized trial, DMPA-IM was not associated with increased risk of HSV-2 acquisition. HSV-2 incidence was >10% per year, emphasizing the need for development of novel HSV-2 prevention strategies for African women. Clinical Trial Registration Details: ClinicalTrials.gov number NCT02550067. Funding Information: The ECHO Trial was made possible by the combined generous support of the Bill & Melinda Gates Foundation, the American people through the United States Agency for International Development and the President’s Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency as part of the EDCTP2 programme supported by the European Union, the South African Medical Research Council, and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and United States Agency for International Development. Additional funding for testing for herpes simplex type 2 infection was provided in part by the US Centers for Disease Control and Prevention (U48 DP 005013 SIP 14-023) and the University of Washington/Fred Hutch Center for AIDS Research (US National Institutes of Health P30 AI057757). Declaration of Interests: None. Ethics Approval Statement: Ethics review committees at each study site approved the study protocol. All participants provided written informed consent, which included counseling about randomization, each study contraceptive method, and their rights as research participants.

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

Background: We assessed the associations between severe food insecurity (SFI) and HIV risk in six sub-Saharan African countries. Methods: Data from nationally representative Population-based HIV Impact Assessments (PHIAs) in Zambia, Eswatini, Lesotho, Uganda, and Tanzania and Namibia were used. SFI was defined as having no food in the house at least three times in the past month. Recent HIV infection was identified using the HIV-1 LAg avidity assay, with viral load (>1000 copies/ml) and antiretroviral data. Logistic regression was conducted to assess correlates of SFI. Poisson regression was conducted on pooled data, stratified by sex and adjusted by country, urbanicity, wealth quintile and age, to determine the association of SFI with recent HIV infection and risk behaviors. All analyses were done using weighted data. Findings: Of the 112,955 survey participants aged 15-59, 10·3% lived in households reporting SFI. SFI was most common in poor, urban, woman-headed households with many dependents. Among women, SFI was associated with a two-fold increase in risk of recent HIV infection (adjusted relative risk [aRR] 2·04, 95% CI 1·04-3·98), and receipt of food support was protective (aRR 0·36, 95% CI 0·14-0·91), associations not observed among men. SFI was also associated with transactional sex (aRR 1·29, 95% CI 1·17-1·41), a history of forced sex (aRR 1·42, 95% CI 1·16-1·74), and condom-less sex with a partner of unknown or positive HIV status (aRR 1·08, 95% CI 1·02-1·14) in all women, and intergenerational sex (sexual partner ≥10 years older) in women aged 15-24 (aRR 1·23, 95% CI 1·03-1·46). Interpretation: The findings demonstrate that food insecurity increases risk for HIV acquisition. Worsening food scarcity due to climactic extremes could imperil HIV epidemic control, while food support programs might mitigate this risk. Funding Information: President’s Emergency Plan for AIDS Relief (PEPFAR) through the US Centers for Disease Control and Prevention under the terms of cooperative agreement #U2GGH001226. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: Written informed consent/assent was documented via electronic signature, with witnesses verifying consent for illiterate individuals. The PHIA protocol and data collection tools were approved by national ethics committees for each country, and the institutional review boards at Columbia University Irving Medical Center, the US Centers for Disease Control and Prevention (CDC) and the University of California, San Francisco in the case of Namibia.

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

IntroductionThe Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a target of ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) to have viral load suppression (VLS). We examined factors associated with nonsuppressed viral Load (NVL).MethodsWe included PLHIV receiving ART aged 15–59 years from Eswatini, Lesotho, Malawi, Zambia, and Zimbabwe. Blood samples from PLHIV were analyzed for HIV RNA and recent exposure to antiretroviral drugs (ARVs). Outcomes were NVL (viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL), and receiving second-line ART. We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART.ResultsThe prevalence of NVL was 11.2%: 8.2% experienced VF, and 3.0% interrupted ART. Younger age, male gender, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married, and residing in Zimbabwe, Lesotho, or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female gender, shorter ART duration, higher CD4 count, and alcohol use were associated with higher odds for interrupted ART and lower odds for VF. Many people with VF (44.8%) had CD4 counts ConclusionsCountries are approaching UNAIDS VLS targets for adults. Treatment support for people initiating ART with asymptomatic HIV infection, scale-up of viral load monitoring, and optimized ART regimens may further reduce NVL prevalence.

ObjectivesReproductive aged women are at risk of pregnancy and sexually transmitted infections (STI). Understanding drivers of STI acquisition, including any association with widely used contraceptives, could help us to reduce STI prevalence and comorbidities. We compared the risk of STI among women randomised to three contraceptive methods.MethodsWe conducted a secondary analysis to assess the risk of chlamydia and gonorrhoea in a clinical trial evaluating HIV risk among 7829 women aged 16–35 randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) or a levonorgestrel (LNG) implant. We estimated chlamydia and gonorrhoea prevalences by contraceptive group and prevalence ratios (PR) using log-binomial regression.ResultsAt baseline, chlamydia and gonorrhoea prevalences were 18% and 5%, respectively. Final visit chlamydia prevalence did not differ significantly between DMPA-IM and copper IUD groups or between copper IUD and LNG implant groups. The DMPA-IM group had significantly lower risk of chlamydia compared with the LNG implant group (PR 0.83, 95% CI 0.72 to 0.95). Final visit gonorrhoea prevalence differed significantly only between the DMPA-IM and the copper IUD groups (PR 0.67, 95% CI 0.52 to 0.87).ConclusionsThe findings suggest that chlamydia and gonorrhoea risk may vary with contraceptive method use. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use.

Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD), and the levonorgestrel (LNG) implant on markers of HIV disease progression at the time of HIV detection and 3 months postdetection and time from detection to CD4 count

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.

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.

Objective: Early initiation of antiretroviral treatment (ART) at CD4+ cell count greater or equal to 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. Design: A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. Methods: Eight to 12 months after a national survey to determine adult HIV prevalence 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4+ cell enumeration VL measurements and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (greater than or equal to 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. Results: Of the 927 (87% of 1067) participants enrolled 466 (50%) reported no ART use. Among them 424 (91%) had VL greater than or equal to 1000 copies per milliliter; of these 148 (35%) were eligible for ART at the then existing CD4+ count threshold of less than 350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4+ criterion of less than 500 cells per microliter; and 169 (40%) remained ART ineligible. Thus 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4+ criterion of less than 500 cells per microliter. Conclusions: A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART. Copyright © 2015 Wolters Kluwer Health Inc.

In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load

Swaziland has the highest national HIV prevalence worldwide. The Swaziland HIV Incidence Measurement Survey (SHIMS) provides the first national HIV incidence estimate based on prospectively observed HIV seroconversions.A two-stage survey sampling design was used to select a nationally representative sample of men and women aged 18-49 years from 14 891 households in 575 enumeration areas in Swaziland, who underwent household-based counselling and rapid HIV testing during 2011. All individuals aged 18-49 years who resided or had slept in the household the night before and were willing to undergo home-based HIV testing, answer demographic and behavioural questions in English or siSwati, and provide written informed consent were eligible for the study. We performed rapid HIV testing and assessed sociodemographic and behavioural characteristics with use of a questionnaire at baseline and, for HIV-seronegative individuals, 6 months later. We calculated HIV incidence with Poisson regression modelling as events per person-years × 100, and we assessed covariables as predictors with Cox proportional hazards modelling. Survey weighting was applied and all models used survey sampling methods.Between Dec 10, 2010, and June 25, 2011, 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232 (94%) were re-tested. Of these, 145 HIV seroconversions were observed, resulting in a weighted HIV incidence of 2·4% (95% CI 2·1-2·8). Incidence was nearly twice as high in women (3·1%; 95% CI 2·6-3·7) as in men (1·7%; 1·3-2·1, p0·0001). Among men, partner's HIV-positive status (adjusted hazard ratio [aHR] 2·67, 1·06-6·82, p=0·040) or unknown serostatus (aHR 4·64, 2·32-9·27, p0·0001) in the past 6 months predicted HIV seroconversion. Among women, significant predictors included not being married (aHR 2·90, 1·44-5·84, p=0·0030), having a spouse who lives elsewhere (aHR 2·66, 1·29-5·45, p=0·0078), and having a partner in the past 6 months with unknown HIV status (aHR 2·87, 1·44-5·84, p=0·0030).Swaziland has the highest national HIV incidence in the world. In high-prevalence countries, population-based incidence measures and programmes that further expand HIV testing and support disclosure of HIV status are needed.President's Emergency Plan for AIDS Relief (PEPFAR) by the Centers for Disease Control and Prevention.

The human immunodeficiency virus (HIV) epidemic has had an extraordinary global impact. Even as it has devastated societies, it has also inspired community empowerment, motivated impressive scientific discoveries, and provoked an unprecedented mobilization of vast resources for a single health condition. Not yet fully realized, however, is the epidemic's potential for expanding the core mission of academic institutions to include the pursuit of a wider range of research. Most universities focus on three core missions: transmitting knowledge to undergraduate students, developing the next generation of scholars through graduate education, and producing new discoveries through research. In both education and research, . . .

This article presents results from a small, introductory clinical study offering a simplified regimen medical abortion to women in Turkey. A total of 208 women from five sites were recruited from July 2000 through March 2001. All eligible consenting women were given 200 mg oral mifepristone at the clinic followed by 400 microg oral misoprostol 2 days later either at home or at the clinic. The overall success rate of 84.1% is lower than in previous studies of this regimen, and a surprisingly high proportion of women (9.1%) were diagnosed with incomplete abortion. In spite of the higher than expected failure rate, women expressed a high degree of satisfaction. Several challenges were faced during this study, providing valuable insights about ways to introduce medical abortion into new settings with the best chances for success.

Medical abortion regimens have become widely used, but the frequency of infection after medical abortion is not well documented. This systematic review provides data on infectious complications after medical abortion. We searched Medline for articles written before July 2003 to determine the frequency of infection after medical abortion up to 26 weeks of gestation. We reviewed all articles and extracted data on the frequency of infection from 65 studies. The frequency of diagnosed and/or treated infection after medical abortion was very low (0.92%, N = 46,421) and varied among regimens. Results of this review confirm that, with respect to infectious complications, medical abortion is a safe and effective option for first- and second-trimester pregnancy termination. After accounting for regional variations in diagnosis, there is little difference in frequency of infection among the regimens reviewed. Future studies should report clear diagnosis and treatment standards for infection so that more precise information becomes available.

OBJECTIVE: Medical abortion regimens have become more widely used to terminate early pregnancies. Medical abortion providers are concerned to diagnose and exclude women with ectopic pregnancy before initiating treatment, as with any early pregnancy termination. Yet, there is little information about whether the various pretreatment screening methods used are adequate. We reviewed published literature to determine the overall success of screening for ectopic pregnancy before medical abortion treatment. DATA SOURCES: We searched MEDLINE for articles on medical abortion regimens published before July 2003. METHODS OF STUDY SELECTION: We selected English language articles of studies of medical abortion with sample sizes greater than 100, which reported on ectopic pregnancy diagnosed after medical abortion treatment. Fifty-seven of 85 prospective studies and randomized trials (69%) met these inclusion criteria. We also included data from 2 unpublished studies because they were large and well-controlled and because they included serious adverse events known to us, which we did not deem fair to exclude from our analysis. TABULATION, INTEGRATION, AND RESULTS: Each article was reviewed by one author. Data from selected studies were compiled, and the frequency of ectopic pregnancy diagnosed after medical abortion treatment was calculated. Ectopic pregnancy was diagnosed very infrequently following medical abortion procedures, occurring in only 10 of 44,789 (0.02%) women. CONCLUSION: The very low frequency of ectopic pregnancies diagnosed after medical abortion treatment demonstrates that the various pretreatment screening methods that providers use to exclude patients with ectopic pregnancies are successful. Further, there is no evidence to suggest that medical abortion treatment leads to unusual complications for women with ectopic pregnancies.

Background The 2011 Swaziland HIV Incidence Measurement Survey (SHIMS) was conducted as part of a national study to evaluate the scale up of key HIV prevention programs. Methods From a randomly selected sample of all Swazi households, all women and men aged 18-49 were considered eligible, and all consenting adults were enrolled and received HIV testing and counseling. In this analysis, population-based measures of HIV prevalence were produced and compared against similarly measured HIV prevalence estimates from the 2006-7 Swaziland Demographic and Health. Also, measures of HIV service utilization in both HIV infected and uninfected populations were documented and discussed. Results HIV prevalence among adults aged 18-49 has remained unchanged between 2006-2011 at 31-32%, with substantial differences in current prevalence between women (39%) and men (24%). In both men and women, between since 2006-7 and 2011, prevalence has fallen in the young age groups and risen in the older age groups. Over a third (38%) of the HIV-infected population was unaware of their infection status, and this differed markedly between men (50%) and women (31%). Of those aware of their HIV-positive status, a higher percentage of men (63%) than women (49%) reported ART use. Conclusions While overall HIV prevalence remains roughly constant, age-specific changes strongly suggest both improved survival of the HIV-infected and a reduction in new HIV infections. Awareness of HIV status and entry into ART services has improved in recent years but remains too low. This study identifies opportunities to improve both HIV preventive and care services in Swaziland.

Background Gaps in the HIV care continuum contribute to suboptimal individual health outcomes and increased risk of HIV transmission at the population level. Implementation science studies are needed to evaluate clinic-based interventions aimed at improving retention of patients across the continuum. Methods/design Link4Health uses an unblended cluster site-randomized design to evaluate the effectiveness of a combination intervention strategy (CIS) as compared to standard of care on linkage to and retention in care among HIV-diagnosed adults in Swaziland. The CIS intervention targets a multiplicity of structural, behavioral, and biomedical barriers through five interventions: (1) point-of-care CD4 testing at time of HIV testing, (2) accelerated antiretroviral therapy (ART) initiation for eligible patients, (3) mobile phone appointment reminders, (4) care and prevention packages, and (5) non-cash financial incentives for linkage and retention. The unit of randomization is a network of HIV clinics inclusive of a secondary facility coupled with an affiliated primary facility. Ten study units were randomized based on implementing partner, geographic location, and historic volume of HIV patients. Target enrollment was 2200 individuals, each to be followed for 12 months. Eligibility criteria includes HIV-positive test, age >18 years, willing to receive HIV care at a clinic in the study unit and consent to study procedures. Exclusion criteria included previous HIV care in the past 6 months, planning to leave the community, and current pregnancy. The primary study outcome is linkage within 1 month and retention at 12 months after testing HIV positive. Secondary outcomes include viral load suppression at 12 months, time to ART eligibility and initiation, participant acceptability, and cost-effectiveness. The trial status is that study enrollment is complete and follow-up procedures are ongoing. Discussion Link4Health evaluates a novel and pragmatic combination intervention strategy to improve linkage to and retention in care among adults with HIV in Swaziland. If the strategy is found to be effective, this study has the potential to inform HIV service delivery in resource-limited settings. Trial registration Clinicaltrials.gov NCT01904994