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BackgroundOrgan transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety.MethodsWe performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors.ResultsBetween March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL

: Introduction: Population‐level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale‐up. Methods: In 2015–2020, we measured VLS ( Results: Overall, 3080 participants contributed 4604 visit‐pairs over three survey rounds. Most visit‐pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow‐up, 91.3% of which was high‐level viraemia. One‐fifth (20.8%) of visit‐pairs exhibiting persistent high‐level viraemia self‐reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high‐level viraemia varied substantially across communities and was significantly elevated among young persons aged 15–29 years (vs. 40‐ to 49‐year‐olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21–3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87–3.07), persons reporting inconsistent condom use with non‐marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10–1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03–1.16). The prevalence of persistent high‐level viraemia was highest among males Conclusions: Following universal ART provision, most persons living with HIV in south‐central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high‐level viraemia for ≥12 months and reported higher‐risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control., INTRODUCTION Universal Test and Treat (UTT) signalled a global paradigm shift in HIV control efforts through expanded antiretroviral therapy (ART) eligibility. Randomized trials in sub‐Saharan Africa demonstrated population‐level benefits of [...]

: Introduction: Antiretroviral treatment (ART) sharing has been reported among fishermen and sex workers in Uganda and South Africa. However, no population‐based studies have documented ART diversion prevalence (including sharing [giving/receiving], buying and selling) or its relationship with viremia among men and women living with HIV in Africa. Methods: In 2018–2020, we surveyed people living with HIV aged 15–49 years in 41 communities in the Rakai Community Cohort Study, a population‐based cohort in south‐central Uganda. We assessed the prevalence and correlates of self‐reported lifetime and past‐year ART diversion, stratifying by age and gender and documenting sources of diverted drugs. We used log‐binomial regression to quantify the relationship between diversion patterns and viremia (viral load >40 copies/ml), reported as unadjusted and adjusted prevalence ratios (aPR) with 95% confidence intervals (CI). Results: Of 2852 people living with HIV and self‐reporting current ART use, 266 (9.3%) reported lifetime ART diversion. Giving/receiving drugs were most common; few participants reported buying, and none reported selling. Men (12.9%) were more likely to report lifetime diversion than women (7.4%), with men aged 25–34 reporting high levels of sharing (18.9%). Friends were the most common sources of shared drugs, followed by spouses/sexual partners. Patterns of lifetime and past‐year diversion were similar. Among participants with viral load results, 8.6% were viraemic. In adjusted analyses, people who reported only giving ART were nearly twice as likely to be viraemic than those who reported no diversion (aPR: 1.94, 95% CI: 1.10−3.44), and those reporting only receiving ART were less likely to exhibit viremia (aPR: 0.46, 95% CI: 0.12−1.79), although the latter was not statistically significant. Reporting both giving and receiving ART was not associated with viremia (aPR: 0.79, 95% CI: 0.43−1.46). Reporting buying ART, though rare, was also correlated with higher rates of viremia, but this relationship was not statistically significant (aPR: 1.98, 95% CI: 0.72−5.45). Conclusions: ART sharing is common among persons reporting ART use in rural Uganda, particularly among men. Sharing ART was associated with viremia, and receiving ART may facilitate viral suppression. HIV programmes may benefit from considering ART sharing in counselling messages., INTRODUCTION Drug diversion is broadly conceptualized as the transfer of prescribed medication from the individual to whom it was prescribed to a different individual [1]. Drug diversion may include sharing [...]

To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these 'source' populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8-28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.

The limiting antigen (LAg)-avidity assay is a serologic assay used for cross-sectional HIV incidence testing. We compared the results obtained with the LAg-avidity assay using dried blood spot (DBS) samples stored at room temperature (18°C-25°C) or stored frozen at -80°C with results obtained from matched plasma samples. Matched DBS and plasma samples (306 paired samples) were collected in the HIV Prevention Trials Network (HPTN) 068 trial in South Africa (2012-2014). The DBS were stored at room temperature before testing. Matched DBS and plasma samples (100 paired samples) from the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) were collected in 2016 and were stored at -80°C. All DBS testing was performed in 2017. Differences in normalized optical density (ODn) were compared between matched DBS and plasma samples. For DBS samples stored at room temperature (HPTN 068), the average difference in ODn values for plasma versus DBS was 1.49 (95% confidence intervals [CI]: 1.36-1.62). In contrast, when DBS samples were stored at -80°C (CEPHIA), the average difference in ODn values for plasma versus DBS was -0.22 (95% CI: -0.32 to -0.13). DBS samples stored at room temperature should not be used for cross-sectional HIV incidence testing with the LAg-avidity assay.

Background Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. Method A cross-sectional analysis of 5496 20–59-year-old participants in the 2009–2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for β-diversity (between-sample heterogeneity). Results Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] =.992–.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI =.90–.99) were associated with high-risk oral HPV infection. β-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R 2 = 0.054%; P =.029) and unweighted UniFrac distance (R 2 = 0.046%; P =.045). There were differential associations when stratified by sex. Conclusions Both oral microbiome α-diversity and β-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the association between cytomegalovirus (CMV) IgG antibody levels, HIV disease progression, and immune activation markers.DesignA prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda.MethodsThe primary endpoints were progression to a CD4 T-cell count less than 250 cells/μl, nontraumatic death, or initiation of antiretroviral therapy (ART). CD4 T-cell counts, HIV viral load, C-reactive protein (CRP), and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibodies were measured at baseline among all women and annually among a subset of women who initiated ART.ResultsThere were 300 HIV/CMV-coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared with the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4 T-cell count, and HIV viral load at baseline [adjusted hazard ratio = 1.59; (95% CI = 1.05-2.39); P = 0.027]. Among pre-ART visits (n = 1200), women in the highest baseline CMV IgG tertile had increasing annual rates of soluble CD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared with pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with soluble CD14 and CRP during suppressive ART (n = 88 person-visits).ConclusionThe magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest. Most studies on HIV-1 proviruses that persist during antiretroviral therapy have focused on males with HIV-1 subtype B, even though the majority of people living with HIV globally have non-B subtypes. Here, the authors describe the proviral genetic landscape of HIV-1 subtypes A1 and D in Ugandan females and males using near-full-length proviral sequencing. The authors also describe a molecular assay for intact proviral quantification of these HIV-1 subtypes. [ABSTRACT FROM AUTHOR]

Background A substantial proportion of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their human immunodeficiency virus (HIV) care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. Methods We used data from 40 communities (2015–2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15–49 years with serologically confirmed HIV who self-reported ART use and contributed ≥1 follow-up visit were included. Facility switching and virologic outcomes were assessed between 2 consecutive study visits (ie, index and follow-up visits, interval of approximately 18 months). Those who reported different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. Results Overall, 2257 persons who self-reported ART use (median age, 35 years; 65% female, 92% initially suppressed) contributed 3335 visit-pairs and 5959 person-years to the analysis. Facility switching was common (4.8 per 100 person-years; 95% confidence interval [CI], 4.2–5.5) and most pronounced in persons aged <30 years and fishing community residents. Among persons suppressed at their index visit (n = 2076), incidence of viral rebound was more than twice as high in persons who switched facilities (adjusted incidence rate ratio = 2.27; 95% CI, 1.16–4.45). Conclusions Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity. [ABSTRACT FROM AUTHOR]

Convalescent plasma is a leading treatment for coronavirus disease 2019 (COVID-19), but there is a paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus neutralization assay with Vero-E6- TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor-binding domain (S-RBD); and an IgG avidity assay. We used multiple linear regression and predictive models to assess the correlations between antibody responses and demographic and clinical characteristics. IgG titers were greater than either IgM or IgA titers for S1, full-length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing antibody (nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed 95%-98% of the nAb-positive samples, but 20%-32% of the nAb-negative samples were still IgG ELISA positive. Male sex, older age, and hospitalization for COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses., Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. Following the rapid, global spread of SARS-CoV-2 [...]

Vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (ART). Vaginal swabs were screened for levels of cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ. The relative risk (RR) of herpes simplex virus-2 or cytomegalovirus (CMV) shedding being associated with cytokine levels above the median were estimated. Herpes simplex virus-2 shedding was significantly associated with higher levels of IL-6 (RR = 1.4, P = .003) and TNF-α (RR = 1.3, P = .010), whereas CMV shedding was associated with higher IL-6 (RR = 1.3, P = .006) and IL-2 (RR = 1.4, P = .01). The association of viral shedding with higher IL-6 levels suggests that herpes virus reactivation may be playing a role in immune activation after ART initiation.

Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding.