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BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

We evaluated the efficacy of a brief motivational intervention (MI) counseling in reducing alcohol consumption among persons living with HIV/AIDS in Kampala, Uganda. Persons living with HIV/AIDS with Alcohol Use Disorders Identification Tool (AUDIT) score ≥3 points were randomized to either standardized positive prevention counseling alone or in combination with alcohol brief MI counseling. The mean change in AUDIT-C scores over 6 months was compared by treatment arm. The mean (standard deviation [SD]) AUDIT-C scores were 6.3 (2.3) and 6.8 (2.3) for control and MI arms ( P = .1) at baseline, respectively, and change in mean AUDIT-C score was not statistically different between arms over the 6 months ( P = .8). However, there was a statistically significant decrease in mean AUDIT-C score (-1.10; 95% confidence interval: -2.19 to -0.02, P = .046) among women in the MI arm. There was a nondifferential reduction in alcohol consumption overall, but MI appeared effective among women only. Studies with more than 1 counseling session and evaluation of gender differences in treatment response are needed.

BackgroundImmune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2).MethodsWe evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated.ResultsGUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups.ConclusionsInitiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.

BackgroundThe efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis.MethodsWe examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts.ResultsTransmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060).ConclusionsCondoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.

BackgroundA heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission - both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.MethodsUsing prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1-susceptible and HIV-1-infected partners. Plasma was collected before seroconversion for cases.ResultsFor both HIV-1-infected and HIV-1-susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T(2) test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1-susceptible and HIV-1-infected case partners, compared with HIV-1-susceptible and HIV-1-infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1-susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1-infected partners (P = .02).ConclusionsImmune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.

H3Africa is developing capacity for health-related genomics research in Africa

Introduction: Women in fishing communities have both high HIV prevalence and incidence, hence they are a priority population for HIV prevention and treatment interventions. However, their mobility is likely to compromise the effectiveness of interventions. We assessed the acceptability, feasibility and of using phones and global positioning system (GPS) devices for tracking mobility, to inform future health research innovations. Methods: A mult-site formative qualitative study was conducted in six purposively selected Fishing Communities on the shores of Lake Victoria in Kenya, Tanzania, and Uganda. Participants were selected based on duration of stay in the community and frequency of movement. Sixty-four (64) women participated in the study (16 per fishing community). Twenty-four (24) participants were given a study phone; 24 were asked to use their own phones and 16 were provided with a portable GPS device to understand what is most preferred. Women were interviewed about their experiences and recommendations on carrying GPS devices or phones. Twenty four (24) Focus Group Discussions with 8–12 participants were conducted with community members to generate data on community perceptions regarding GPS devices and phones acceptability among women. Data were analyzed thematically and compared across sites/countries. Results: Women reported being willing to use tracking devices (both phones and GPS) because they are easy to carry. Their own phone was preferred compared to a study phone and GPS device because they were not required to carry an additional device, worry about losing it or be questioned about the extra device by their sexual partner. Women who carried GPS devices suggested more sensitization in communities to avoid domestic conflicts and public concern. Women suggested changing the GPS colour from white to a darker colour and, design to look like a commonly used object such as a telephone Subscriber Identity Module (SIM) card, a rosary/necklace or a ring for easy and safe storage. Conclusion: Women in the study communities were willing to have their movements tracked, embraced the use of phones and GPS devices for mobility tracking. Devices need to be redesigned to be more discrete, but they could be valuable tools to understanding movement patterns and inform design of interventions for these mobile populations. [ABSTRACT FROM AUTHOR]

BackgroundPreexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others.MethodsIn this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety.ResultsHIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P

BackgroundThe Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort.MethodsHIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed.ResultsOf the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to

Background: Routine adolescent health screening aiming at the detection of unnoticed medical problems may increase awareness among policy makers and contribute to improved health in this population. Research is needed to inform the World Health Organization (WHO) and national health programs to provide evidence-based guidance on whether public health systems should offer comprehensive adolescent health screening, what should be included in different contexts, and how it should be delivered. We conducted formative research to define the content and delivery strategies for health check-ups to be performed in young (10–14 years) and older (15–19 years) adolescents, and to assess whether such services are likely to be acceptable and feasible in Tanzania. Methods: As part of a collaborative research program coordinated by WHO in Chitungwiza, Zimbabwe; Mwanza City, Tanzania; and Cape Coast, Ghana a series of key informant interviews were conducted from April to July 2020, using a semi-structured guide with purposively selected stakeholders from government departments, non-governmental and community-based organisations, schools and health facilities. Data transcripts were coded using NVivo 12 software and thematic analysis was performed. Results: We report results from 31 key informant interviews to address four main domains: proposed health conditions for routine health check-ups, health interventions to be combined with such check-ups, preferable venues, and the mode for delivering such screening activities. Stakeholders were supportive of introducing routine health check-ups among adolescents. They recommended focusing on non-communicable diseases, physical disabilities, common mental health problems, reproductive health problems, specific communicable diseases, and hygiene-related problems. They also recommended combining counselling and family planning information with these check-ups. Three venues were proposed: schools, community settings (to reach out-of-school adolescents), and youth-friendly health facilities (for conditions requiring a high level of confidentiality). Conclusions: Stakeholders were supportive of the proposed routine health check-ups for adolescents, recommending specific health conditions to be screened for in both community and school settings. Based on the above, we plan to conduct implementation research to determine the number of new treatable conditions detected, and the costs of offering such services. In the longer term, evaluation of their health impact and cost-effectiveness will be required to guide policy. [ABSTRACT FROM AUTHOR]