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Background: Indeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and its sociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda., Methods: 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15-49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results., Results: The prevalence of HIV serologically indeterminate results was 4.9%. Indeterminate results were less likely among women than men (adjPR 0.76, 95% CI 0.71,0.81), in unmarried participants than married participants (adjPR 0.92, 95% CI 0.85,99), and in individuals with primary (adjPR 0.90, 95% CI 0.80,1.02), secondary (adjPR 0.83, 95% CI 0.73,0.96) and post-secondary (adjPR 0.75, 95% CI 0.60,0.94) education, relative to no education. The proportions of persons with indeterminate results progressing to HIV positive, negative or indeterminate results in subsequent visits was 5%, 71% and 24%, respectively., Conclusion: HIV serologically indeterminate results were associated with gender and marital status. HIV surveillance programs should develop a protocol for reporting individuals with mixed or persistently indeterminate HIV results on multiple follow-up visits. Most indeterminate results became HIV-negative over time, but follow-up is still needed to detect positive serologies., Competing Interests: The authors have declared that no competing interests exist.

Background: The rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment., Methods: We carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect of a family economic empowerment (EE) intervention on viral suppression in five districuts in Uganda. In total, 39 accredited health care clinics from study districts with existing procedures tailored to adolescent adherence were eligible to participate in the trial. We used data from 288 youth with detectable HIV viral loads (VL) at baseline (158 -intervention group from 20 clinics, 130 -non-intervention group from 19 clinics). The primary end point was undetectable plasma HIV RNA levels, defined as < 40 copies/ml. We used Kaplan-Meier (KM) analysis and Cox proportional hazard models to estimate intervention effects., Findings: The Kaplan-Meier (KM) analysis indicated that an incidence of undetectable VL (0.254) was significantly higher in the intervention condition compared to 0.173 (in non-intervention arm) translated into incidence rate ratio of 1.468 (CI: 1.064-2.038), p = 0.008. Cox regression results showed that along with the family-based EE intervention (adj. HR = 1.446, CI: 1.073-1.949, p = 0.015), higher number of medications per day had significant positive effects on the viral suppression (adj.HR = 1.852, CI: 1.275-2.690, p = 0.001)., Interpretation: A family economic empowerment intervention improved treatment success for ALWHIV in Uganda. Analyses of cost effectiveness and scalability are needed to advance incorporation of this intervention into routine practice in low and middle-income countries., Competing Interests: The authors have declared that no competing interests exist.

Background: Medical male circumcision (MC) of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda., Methods: 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE)., Results: Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧ 350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005). Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef.  = -0.134, p<0.001)., Conclusion: We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.

Previous studies demonstrated that individuals with subtype D HIV infection who had been infected for 2 or more years were frequently misclassified as assay positive using cross-sectional incidence assays. Samples from 510 subjects (212 subtype A, 298 subtype D) who were infected for 2.2 to 14.5 years (median 5.4 years) and were not virally suppressed were tested using an LAg-Avidity enzyme immunoassay (LAg-Avidity EIA), Bio-Rad Avidity assay, and BED capture enzyme immunoassay (BED-CEIA). The performance of these three assays was evaluated using various assay cutoff values [LAg-Avidity EIA: <1.0 OD-n and <2.0 OD-n; Bio-Rad Avidity assay: <40% avidity index (AI) and <80% AI; BED-CEIA: <0.8 OD-n]. The mean LAg-Avidity EIA result was higher for subtype A than D (4.54±0.95 vs. 3.86±1.26, p<0.001); the mean Bio-Rad Avidity assay result was higher for subtype A than D (88.9%±12.5% vs. 75.1±30.5, p<0.001); and the mean BED-CEIA result was similar for the two subtypes (2.2±1.2 OD-n for subtype A, 2.2±1.3 OD-n for subtype D, p<0.9). The frequency of misclassification was higher for individuals with subtype D infection compared to those with subtype A infection, using either the LAg-Avidity EIA with a cutoff of <2.0 OD-n or the Bio-Rad Avidity assay with cutoffs of <40% or <80% AI. No subtype-specific differences in assay performance were observed using the BED-CEIA. Sex and age were not significantly associated with misclassification by any assay. The LAg-Avidity EIA with a cutoff <1.0 OD-n had the lowest frequency of misclassification in this Ugandan population.

Background: Male circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners., Methods: Female partners of HIV-infected men (aged 15-49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878., Findings: 474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1·07, 95% CI 0·86-1·32, p=0·64). Incidence of high-risk HPV over 2 years was 32·0 per 100 person-years in the female partners of men in the intervention group and 30·6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1·05, 0·77-1·43, p=0·78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0·96, 0·83-1·12; p=0·61)., Interpretation: Because circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important., Funding: Bill & Melinda Gates Foundation and National Institutes of Health., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC., Methods and Findings: HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43-0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51-0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30-0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (chi(2)p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15-0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19-1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49-1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0-38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI -1.2 to 77.1)., Conclusions: Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.

Intimate partner violence (IPV) has been associated with delays throughout the HIV care continuum. This study explored prospective associations between experiences of past-year IPV and two HIV care outcomes in the context of current universal test and treat guidelines using two consecutive rounds of an ongoing HIV surveillance study conducted in the Rakai region of Uganda. Longitudinal logistic regression models examined associations between IPV, use of antiretroviral therapy (ART) and viral load suppression (VS), adjusting for outcome variables at baseline. To address differences in ART retention by IPV, propensity scores were used to create inverse-probability-of-treatment-and-censoring-weighted (IPTCW) models. At baseline, of 1923 women with HIV (WWH), 34.6%, 26.5%, 13.5% reported past-year verbal, physical and sexual IPV; a lower proportion of persons who experienced physical IPV (79.4%) were VS than those who did not (84.3%; p = 0.01). The proportion VS at baseline also significantly differed by exposure to verbal IPV (p = 0.03). However, in adjusted longitudinal models, IPV was not associated with lower odds of ART use or VS at follow-up. Among WWH in the Rakai region, IPV does not appear to be a barrier to subsequent ART use or VS. However, given the prevalence of IPV in this population, interventions are needed.

The syndemic relationship between harmful alcohol use, intimate partner violence (IPV), and HIV is well established across international settings. Less is known about how these health issues are perceived by women living with HIV (WLWH), who are disproportionately affected by these intertwined epidemics. A qualitative study was undertaken with 20 WLWH in Rakai, Uganda, to assess their perceptions of how these issues have affected their lives and their communities and to assess the acceptability of integrating a screening and brief intervention for alcohol use and IPV into HIV posttest counseling. Recommendations for intervention programming arising from the results are discussed.

The syndemic relationship between harmful alcohol use, intimate partner violence (IPV), and HIV is well established across international settings. Less is known about how these health issues are perceived by women living with HIV (WLWH), who are disproportionately affected by these intertwined epidemics. A qualitative study was undertaken with 20 WLWH in Rakai, Uganda, to assess their perceptions of how these issues have affected their lives and their communities and to assess the acceptability of integrating a screening and brief intervention for alcohol use and IPV into HIV posttest counseling. Recommendations for intervention programming arising from the results are discussed.

Transactional sex (TS) is prevalent in sub-Saharan Africa. Women's engagement in TS is linked with HIV infection; little is known about the relationship between TS, intimate partner violence (IPV) and alcohol use-established HIV risk behaviors. Using modified Poisson regression, we assessed associations between TS and physical, verbal and sexual IPV among 8248 women (15-49 years) who participated in the Rakai Community Cohort Study across forty communities in Uganda. An interaction term assessed moderation between alcohol use and TS and no significant interaction effects were found. In adjusted analysis, alcohol use and TS were significantly associated with all forms of IPV. In stratified analysis, TS was only associated with IPV in agrarian communities; alcohol use was not associated with physical IPV in trade communities or sexual IPV in trade and fishing communities. Identifying differences in IPV risk factors by community type is critical for the development of tailored interventions.

Background The impact of migration on HIV risk among non-migrating household members is poorly understood. We measured HIV incidence among non-migrants living in households with and without migrants in Uganda. Methods We used four survey rounds of data collected from July 2011 to May 2018 from non-migrant participants aged 15–49 years in the Rakai Community Cohort Study. Non-migrants were individuals with no-migration between surveys or at the prior survey. Household migration was defined as ≥1 household member migrating into or out of the house from another community between surveys (∼18 months). Incident HIV was defined as testing HIV seropositive following a negative result. Incidence rate ratios (IRRs) were estimated using Poisson regression with generalized estimating equations. Analyses were stratified by gender, migration into or out of the household and the relationship between non-migrants and migrants (e.g. spouse, child). Results About 11 318 non-migrants (5674 women) were followed for 37 320 person-years. Twenty-eight percent (6059/21 370) of non-migrant person-visits had recent migration into or out of the household, and 240 HIV incident cases were identified. Overall, non-migrants in migrant households were not at greater risk of acquiring HIV than non-migrants in households without any migration. However, men were significantly more likely to acquire HIV if their spouse had recently migrated in [adjusted IRR: 2.12; 95% confidence interval (CI): 1.05–4.27] or out (adjusted IRR: 4.01; 95% CI, 2.16–7.44) compared with men with no spousal migration. Conclusions HIV incidence is higher among non-migrant men with migrant spouses. Targeted HIV testing and prevention interventions like pre-exposure prophylaxis could be considered for men with migrant spouses. [ABSTRACT FROM AUTHOR]

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 (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population‐based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low‐level (200–999 copies/ml) or high‐level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit‐pairs; ∼18‐month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow‐up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community‐level prevalence and individual‐level predictors of persistent high‐level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. 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 <30 years (32.0%). 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. [ABSTRACT FROM AUTHOR]

Background Herpes simplex virus type 2 (HSV-2) is an incurable sexually transmitted infection associated with increased risk of acquiring and transmitting human immunodeficiency virus (HIV). HSV-2 is highly prevalent in sub-Saharan Africa, but population-level estimates of incidence are sparse. Methods We measured HSV-2 prevalence from cross-sectional serological data among adults aged 18–49 years in 2 south-central Uganda communities (fishing, inland). We identified risk factors for seropositivity, then inferred age patterns of HSV-2 with a Bayesian catalytic model. Results HSV-2 prevalence was 53.6% (n = 975/1819; 95% confidence interval, 51.3%–55.9%). Prevalence increased with age, was higher in the fishing community, and among women, reaching 93.6% (95% credible interval, 90.2%–96.6%) by age 49 years. Factors associated with HSV-2 seropositivity included more lifetime sexual partners, HIV positive status, and lower education. HSV-2 incidence peakied at age 18 years for women and 19–20 years for men. HIV prevalence was up to 10-fold higher in HSV-2–positive individuals. Conclusions HSV-2 prevalence and incidence were extremely high, with most infections occurring in late adolescence. Interventions against HSV-2, such as future vaccines or therapeutics, must target young populations. Remarkably higher HIV prevalence among HSV-2–positive individuals underscores this population as a priority for HIV prevention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Long-acting injectable antiretroviral treatment (LAI ART), such as a bimonthly injection of cabotegravir/rilpivirine, is a promising HIV treatment option. LAI ART may particularly benefit people who are reluctant to initiate or are poorly adherent to daily oral pills and not virally suppressed. However, the acceptability and feasibility of LAI ART among individuals with viremia in Africa has not been well studied. We conducted qualitative in-depth interviews with 38 people living with HIV with viral load ≥1000 copies/mL and 15 medical and nursing staff, and 6 focus group discussions with peer health workers, to examine acceptability and feasibility of LAI ART in south-central Uganda. Transcripts were thematically analyzed through a team-based framework approach. Most people living with HIV reacted positively toward LAI ART and endorsed interest in taking it themselves. Most felt LAI ART would make adherence easier by reducing the challenge with remembering daily pills, particularly in the context of busy schedules, travel, alcohol use, and dietary requirements. Participants also appreciated the privacy of injections, reducing the likelihood of stigma or inadvertent HIV serostatus disclosure with pill possession. Concerns about LAI ART included side effects, perceived medication effectiveness, fear of injection, and medical mistrust and conspiracy beliefs. Health workers and participants with viremia also noted health system challenges, such as stockouts and monitoring treatment failure. However, they felt the health system could overcome these challenges. Implementation complexities must be addressed as LAI ART is introduced and expanded in Africa to best support viral suppression and address HIV care continuum gaps. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa (SSA), disclosure of HIV status to children remains low. Few studies have examined how children navigate and come to terms with their HIV status. The aim of this study was to explore experiences of children about disclosure of their HIV status. Methods: Between October 2020 and July 2021, 18 purposively selected children aged between 12–17 whose HIV status had been disclosed to them by their caregivers or healthcare providers (HCPs) were recruited for this study. We conducted 18 in-depth interviews (IDIs) to collect data for this study. Data were analyzed using the semantic thematic analysis approach. Results: Primary data obtained through IDIs revealed that disclosure of HIV status to children occurred as a one-time event without pre—disclosure preparatory planning or focused post disclosure follow-up counseling irrespective of the discloser. Post disclosure psycho-social experiences elicited mixed responses. Some children experienced insults and belittlement and stigma and discrimination in the family and community for out-of-school children and at school for school-going children. Positive disclosure experiences involved receiving support to improve ART adherence through constantly being reminded to take their medications timely at the workplace, by supervisors, for working children and by teachers, at school for school-going children. Conclusions: This research contributes to knowledge about children' s experiences of being HIV infected and can specifically be used to improve disclosure strategies. [ABSTRACT FROM AUTHOR]

Point of care rapid recency testing for HIV-1 may be a cost-effective tool to identify recently infected individuals for incidence estimation, and focused HIV prevention through intensified contact tracing. We validated the Asante™ HIV-1 rapid recency® assay for use in Uganda. Archived specimens (serum/plasma), collected from longitudinally observed HIV-1 recently and long-term infected participants, were tested with the Asante HIV-1 rapid recency assay per manufacturer's instructions. Previously identified antiretroviral therapy (ART)-naive samples with known seroconversions within 6 months of follow-up were tested in independent laboratories: the Rakai Health Sciences Program (RHSP) and the Uganda Virus Research Institute HIV Reference Laboratory (UVRI-HRL). In addition, samples from participants who seroconverted within 6–18 months and samples from individuals with chronic HIV-1 infection of at least 18 months duration were classified into three categories: ART naive, ART exposed with suppressed viral loads, and ART exposed with detectable viremia. Of the 85 samples seroconverting in ≤6 months, 27 and 42 samples were identified as "recent" by the Asante HIV-1 rapid recency test at the RHSP laboratory and UVRI-HRL, corresponding to sensitivities of 32% and 49%, respectively. There was 72% agreement between the laboratories (Cohen's kappa = 0.481, 95% CI = 0.317–0.646, p < .0001). Specificity was 100% (200/200) among chronically infected ART-naive samples. The Asante HIV-1 rapid recency assay had low sensitivity for detection of recent HIV-1 infections in Uganda, with substantial interlaboratory variability due to differential interpretation of the test strip bands. Specificity was excellent. Assessment of assay performance in other settings is needed to guide decisions on test utility. [ABSTRACT FROM AUTHOR]

Background: There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa.Methods: Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression.Results: There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15-29 vs 40-49 years; adjRR = 1.80; 95% CI = 1.19-2.71), male sex (adjRR = 2.09, 95% CI = 1.47-2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34-2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34-2.73) were factors associated with persistent viremia.Conclusions: Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic. [ABSTRACT FROM AUTHOR]

Background: People living with HIV are at increased risk for cardiovascular disease (CVD). In sub-Saharan Africa, population-based data on major CVD events such as stroke and myocardial infarction are difficult to collect. The use of proxy measures could be a feasible way to better study CVD in such settings. This study aimed to determine the acceptance of incorporating ECG and arterial function measurements into a population-based cohort study and to assess the prevalence of ECG abnormalities and arterial stiffness. Methods: A pilot study was conducted within the Rakai Community Cohort Study in Uganda on two high-risk CVD populations; one determined by age (35-49) and Framingham CVD risk scores and the other by age alone (50+). Data on ECG, arterial function, blood pressure, and HIV status were collected. The acceptability of incorporating ECG and arterial function measurements was established as an acceptance rate difference of no more than 5% to blood pressure measurements. Results: A total of 118 participants were enrolled, 57 participants living with HIV and 61 HIVnegative participants. Both ECG measurements and arterial function were well accepted (2% difference). Left ventricular hypertrophy (LVH) and arterial stiffness (>10 m/s) were common in both participants living with HIV and HIV-negative participants across the two high-risk populations. Prevalence rates ranged from 30% to 53% for LVH and 25% to 58% for arterial stiffness. Arterial stiffness at the 11 m/s cutoff (p = 0.03) was found to be more common among participants living with HIV in the 35-49 population. Conclusions: The incorporation of ECG and arterial function measurements into routine activities of a population-based cohort was acceptable and incorporating these proxy measures into cohort studies should be explored further. LVH and arterial stiffness were both common irrespective of HIV status with arterial stiffness potentially more common among people living with HIV. [ABSTRACT FROM AUTHOR]

There are limited data on the impact of antiretroviral therapy (ART) on population-level adult mortality in sub-Saharan Africa. We analysed data for 2000-14 from the Rakai Community Cohort Study (RCCS) in Uganda, where free ART was scaled up after 2004. Using non-parametric and parametric (Weibull) survival analysis, we estimated trends in average person-years lived between exact ages 15 and 50, per capita life-years lost to HIV, and the mortality hazards of people living with HIV (PLHIV). Between 2000 and 2014, average adult life-years lived before age 50 increased significantly, from 26.4 to 33.5 years for all women and from 28.6 to 33.8 years for all men. As of 2014, life-years lost to HIV had declined significantly, to 1.3 years among women and 0.4 years among men. Following the roll-out of ART, mortality reductions among PLHIV were initially larger in women than men, but this is no longer the case. [ABSTRACT FROM AUTHOR]

HIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from ~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas. HIV prevalence varies throughout Africa, but the contribution of migration remains unclear. Using population-based data from ~22,000 persons, Grabowski et al. show that HIV-positive migrants selectively migrate to high prevalence areas and that out-migrants from these areas geographically disperse. [ABSTRACT FROM AUTHOR]

Introduction: Tetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV). Objective: To determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision. Methods: We enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response. Results: Mean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35–0.53) on day 0, 3.86IU/ml (CI 3.60–4.11) on day 14, 4.05IU/ml (CI 3.81–4.29) on day 28, and 4.48IU/ml (CI 4.28–4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years. Conclusion: Insufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years. [ABSTRACT FROM AUTHOR]

Introduction: To assess progress towards the UNAIDS 90-90-90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. Methods: Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ² test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART). Results: From September 2013 through December 2015, 3,666 HIV-positive participants were identified in the RCCS. As of December 2015, 98% had received HIV Counseling and Testing (HCT), 74% were enrolled in HIV care, and 63% had initiated ART of whom 92% were virally suppressed after 12 months on ART. Engagement in care was lower among men than women (enrolment in care: adjPRR 0.84, 95% CI 0.77-0.91; ART initiation: adjPRR 0.75, 95% CI 0.69-0.82), persons aged 15-24 compared to those aged 30-39 (enrolment: adjPRR 0.72, 95% CI 0.63-0.82; ART: adjPRR 0.69, 95%CI 0.60-0.80), unmarried persons (enrolment: adjPRR 0.84, 95% CI 0.71-0.99; ART adjPRR 0.80, 95% CI 0.66-0.95), and new in-migrants (enrolment: adjPRR 0.75, 95% CI 0.67-0.83; ART: adjPRR 0.76, 95% CI 0.67-0.85). This cohort achieved 98-65-92 towards the UNAIDS "90-90-90" targets with an estimated 58% of the entire HIV-positive RCCS population virally suppressed. Conclusions: This cohort achieved over 90% in both HCT and viral suppression among ART users, but only 65% in initiating ART, likely due to both an ART eligibility criterion of <500 CD4 cells/mL and suboptimal entry into care among men, younger individuals, and in-migrants. Interventions are needed to promote enrolment in HIV care, particular for hard-to-reach subpopulations. [ABSTRACT FROM AUTHOR]

Background: Although fishing communities have a significantly higher HIV prevalence than the general population, there is paucity of data on the burden of HIV and service utilization, particularly among the youth. We assessed the HIV prevalence and utilization of HIV prevention and treatment services among youth in Kasensero fishing community and the neighboring communities.Method: Data were derived from the Rakai Community Cohort Study (RCCS) surveys conducted between 2013 and 2014. The RCCS is a population-based household survey that collects data annually from individuals aged 15-49 years, resident in 48 communities in Rakai and neighboring districts in Uganda. For this analysis, socio-demographic, behavioral and HIV-related data were obtained for 792 individuals aged 15-24 years. We used logistic regression to conduct bivariate and multivariable analysis to determine the factors that are independently associated with HIV-positive status and their corresponding 95% confidence intervals. Data were analyzed using STATA version 13.Results: Overall HIV prevalence was 19.7% (n = 155); higher in Kasensero (n = 141; 25.1%) and Gwanda (n = 8; 11%) than in Kyebe (n = 6; 3.9%), p < 0.001 and among females (n = 112; 26.0%) than males (n = 43; 12.0%), p < 0.001. Uptake of HIV testing was high in both HIV-positive (n = 136; 89.5%) and HIV-negative youth (n = 435; 92%). Consistent condom use was virtually non-existent in HIV-positive youth (n = 1; 0.6%) compared to HIV-negative youth (n = 20; 4.2%). Only 22.4% (n = 34) of the HIV-positive youth were receiving antiretroviral therapy (ART) in 2013-2014; higher in the HIV-positive females (n = 31; 28.4%) than HIV-positive males (n = 03; 6.7%). Slightly more than half of males (n = 134; 53.8%) reported that they were circumcised; the proportion of circumcised youth was higher among HIV-negative males (n = 122; 58%) than HIV-positive males (n = 12; 27.9%). Factors significantly associated with HIV-positive status included living in Kasensero landing site (adjusted Odds Ratio [aOR] = 5.0; 95%CI: 2.22-13.01) and reporting one (aOR = 5.0; 95%CI: 1.33-15.80) or 2+ sexual partners in the past 12 months (aOR = 11.0; 95% CI; 3.04-36.72).Conclusion: The prevalence of HIV is high especially among young females and in landing site communities than in the peripheral communities. Uptake of HIV prevention and treatment services is very low. There is an urgent need for youth-friendly services in these communities. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-negative or HIV-positive couples followed longitudinally.Methods: Genital HPV was assessed in 725 concordant HIV-negative couples and 209 HIV-positive couples enrolled in a male circumcision trial in Rakai, Uganda, using the Roche Linear Array assay, which detects 37 HPV genotypes. Human papillomavirus prevalence and determinants of genotype-specific concordance were assessed at annual visits. Cumulative detection of HPV genotypes over 2 years was also assessed.Results: At enrollment, HPV infection was detected in 54% of HIV-negative women, 56% of HIV-negative men, and 93% of HIV-positive men and women. For HIV-negative couples, genotypic concordance was 30% at baseline (n = 219/725) and declined significantly with age (adjusted prevelance risk ratio [adjPRR] = 0.53; 95% confidence interval [CI] = 0.28-0.93 comparing women aged >40 years to those aged 15-19 years) and male circumcision (adjPRR = 0.60; 95% CI = 0.47-0.77) and increased among couples with recent intercourse (adjPRR = 1.26; 95% CI = 1.04-1.53). These associations were not seen in HIV-positive couples. Among couples with HPV results at all visits, ≥1 of the same genotypes were detected in both partners in 60% of HIV-negative couples and 96% of HIV-positive couples over 2 years.Conclusion: Human papillomavirus genotype-specific concordance is more common in HIV-positive couples, and irrespective of HIV status, the majority of couples exhibit HPV concordance over 2 years. [ABSTRACT FROM AUTHOR]

Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95%CI 1.04–6.40) and Monokine Induced by γ-interferon (MIG aOR 2.72, 95%CI 1.15–8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man’s female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95%CI 0.44–0.87), and continued to decline for at least two years (PRR 0.29, 95%CI 0.16–0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision. [ABSTRACT FROM AUTHOR]

Background: The association between partner human papillomavirus (HPV) viral load and incident HPV detection in heterosexual couples is unknown.Methods: HPV genotypes were detected in 632 human immunodeficiency virus (HIV)-negative couples followed for 2 years in a male circumcision trial in Rakai, Uganda, using the Roche HPV Linear Array. This assay detects 37 genotypes and provides a semiquantitative measure of viral load based on the intensity (graded 1-4) of the genotype-specific band; a band intensity of 1 indicates a low genotype-specific HPV load, whereas an intensity of 4 indicates a high load. Using Poisson regression with generalized estimating equations, we measured the association between partner's genotype-specific viral load and detection of that genotype in the HPV-discordant partner 1 year later.Results: Incident detection of HPV genotypes was 10.6% among men (54 of 508 genotype-specific visit intervals) and 9.0% among women (55 of 611 genotype-specific visit intervals). Use of male partners with a baseline genotype-specific band intensity of 1 as a reference yielded adjusted relative risks (aRRs) of 1.14 (95% confidence interval [CI], .58-2.27]) for incident detection of that genotype among women whose male partner had a baseline band intensity of 2, 1.75 (95% CI, .97-3.17) among those whose partner had an intensity of 3, and 2.52 (95% CI, 1.40-4.54) among those whose partner had an intensity of 4. Use of female partners with a baseline genotype-specific band intensity of 1 as a reference yielded an aRR of 2.83 (95% CI, 1.50-5.33) for incident detection of that genotype among men whose female partner had a baseline band intensity of 4. These associations were similar for high-risk and low-risk genotypes. Male circumcision also was associated with significant reductions in incident HPV detection in men (aRR, 0.53 [95% CI, .30-.95]) and women (aRR, 0.42 [95% CI, .23-.76]).Conclusions: In heterosexual couples, the genotype-specific HPV load in one partner is associated with the risk of new detection of that genotype in the other partner. Interventions that reduce the HPV load may reduce the incidence of HPV transmission. [ABSTRACT FROM AUTHOR]

Objectives: To assess the safety and acceptance of the PrePex device for medical male circumcision (MMC) in rural Uganda. Methods: In an observational study, HIV-uninfected, uncircumcised men aged 18 and older who requested elective MMC were informed about the PrePex and dorsal slit methods and offered a free choice of their preferred procedure. 100 men received PrePex to assess preliminary safety (aim 1). An additional 329 men, 250 chose PrePex and 79 chose Dorsal slit, were enrolled following approval by the Safety Monitoring Committee (aim 2). Men were followed up at 7 days to assess adverse events (AEs) and to remove the PrePex device. Wound healing was assessed at 4 weeks, with subsequent weekly follow up until completed healing. Results: The PrePex device was contraindicated in 5.7% of men due to a tight prepuce or phimosis/adhesions. Among 429 enrolled men 350 (82.0%) got the PrePex device and 79 (18.0%) the dorsal slit procedure. 250 of 329 men (76.0%) who were invited to choose between the 2 procedures chose Prepex. There were 9 AEs (2.6%) with the PrePex, of which 5 (1.4%) were severe complications, 4 due to patient self-removal of the device leading to edema and urinary obstruction requiring emergency surgical circumcision, and one due to wound dehiscence following device removal. 71.8% of men reported an unpleasant odor prior to PrePex removal. Cumulative rates of completed wound healing with the PrePex were 56.7% at week 4, 84.8% week 5, 97.6% week 6 and 98.6% week 7, compared to 98.7% at week 4 with dorsal slit (p<0.0001). Conclusion: The PrePex device was well accepted, but healing was slower than with dorsal slit surgery. Severe complications, primarily following PrePex self-removal, required rapid access to emergency surgical facilities. The need to return for removal and delayed healing may increase Program cost and client burden. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus (HIV)–infected (HIV+) men are more susceptible to sexually transmitted infections, and may be superinfected by HIV. We hypothesized that HIV induces immune alterations in the foreskin that may impact the subsequent acquisition/clearance of genital coinfections.Methods. Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men undergoing circumcision. T cells were characterized by flow cytometry, immunohistochemistry, and polymerase chain reaction.Results. There was substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1 cells/mm2; P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm2; P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/µL; P < .001). While frequencies of foreskin C-C chemokine receptor type 5+ (CCR5+) T cells, T regulatory cells, and T-helper 17 cells were unaltered in HIV+ men, CD8 T-cell production of tumor necrosis factor α (TNFα) was decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men, although their frequency and function was reduced compared to the blood.Conclusions. Foreskin CD4 T-cell density and CCR5 expression were not reduced during HIV infection, perhaps explaining susceptibility to HIV superinfection. Foreskin CD8 T-cell density was increased, but decreased production of TNFα may enhance susceptibility to genital coinfections in HIV+ men. [ABSTRACT FROM AUTHOR]

Introduction: Targeting most-at-risk individuals with HIV preventive interventions is cost-effective. We developed gender-specific indices to measure risk of HIV among sexually active individuals in Rakai, Uganda. Methods: We used multivariable Cox proportional hazards models to estimate time-to-HIV infection associated with candidate predictors. Reduced models were determined using backward selection procedures with Akaike's information criterion (AIC) as the stopping rule. Model discrimination was determined using Harrell's concordance index (c index). Model calibration was determined graphically. Nomograms were used to present the final prediction models. Results: We used samples of 7,497 women and 5,783 men. 342 new infections occurred among females (incidence 1.11/100 person years,) and 225 among the males (incidence 1.00/100 person years). The final model for men included age, education, circumcision status, number of sexual partners, genital ulcer disease symptoms, alcohol use before sex, partner in high risk employment, community type, being unaware of a partner's HIV status and community HIV prevalence. The Model's optimism-corrected c index was 69.1 percent (95% CI = 0.66, 0.73). The final women's model included age, marital status, education, number of sex partners, new sex partner, alcohol consumption by self or partner before sex, concurrent sexual partners, being employed in a high-risk occupation, having genital ulcer disease symptoms, community HIV prevalence, and perceiving oneself or partner to be exposed to HIV. The models optimism-corrected c index was 0.67 (95% CI = 0.64, 0.70). Both models were well calibrated. Conclusion: These indices were discriminative and well calibrated. This provides proof-of-concept that population-based HIV risk indices can be developed. Further research to validate these indices for other populations is needed. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety of medical male circumcision (MMC) among human immunodeficiency virus (HIV)–infected men with CD4 levels <350 cells/mm3, CD4 counts ≥350 cells/mm3, and HIV-negative men. Methods: Two hundred forty-two HIV-infected men and a sample of 262 HIV-negative consenting men aged 12 years or older who requested free MMC were enrolled in a prospective study. Blood for HIV testing and a CD4 count were collected before surgery. During weekly follow-up over 6 weeks, data were collected on wound healing and adverse events (AEs) by examination, and resumption of sex and condom use ascertained by interview. Surgery-related AEs were characterized by type, severity, management, and resolution. Chi-square and Fisher's exact tests were used to test for differences in AE proportions. Results: Overall, only 2 of the 453 men experienced moderate AEs, a rate of 0.44 per 100 surgeries. No AE occurred among HIV-negative men, whereas the AE rate among HIV-infected men with CD4 counts ≥350 cells/mm3 was 0.79 per 100 surgeries, and among men with CD4 counts <350 cells/mm3 the rate was 1.19 per 100 surgeries (P = .214). AE rates were comparable for all characteristics (P >.05). Conclusion: HIV-positive men can be safely included in MMC roll out programs without necessitating presurgery CD4 counts determination. [Copyright &y& Elsevier]

Objective To assess completed wound healing after medical male circumcision ( MMC) among human immunodeficiency virus ( HIV)-negative and HIV-positive men with cluster of differentiation 4 (CD4) counts of <350 and ≥350 cells/mm3, as minimal data are available on the safety of MMC among HIV-positive men with low CD4 counts., Patients and Methods In all, 262 HIV-negative and 177 HIV-positive consenting males aged ≥12 years accepted MMC using the dorsal slit procedure and were enrolled in the study., Socio-demographic and behavioural data and blood for HIV testing and CD4 counts were collected at baseline., Participants were followed weekly to collect information on resumption of sex, condom use and both self-reported and clinically assessed wound healing., The proportions healed among HIV-positive men were compared with HIV-negative men. Time to complete wound healing was assessed by Kaplan-Meier survival analysis., Results There were no statistically significant differences in the proportion of men healed by HIV status., At 4 weeks, the proportions healed were 85.9% in HIV-negative men, 77.4% in HIV-positive men with a CD4 count of ≥350 cells/mm3 and 87.1% in HIV-positive men with a CD4 count of <350 cells/mm3., The median time to healing was 4 weeks and did not vary by HIV or CD4 status., All men had certified complete wound healing at 6 weeks after MMC. In all, 1.4% of HIV-positive men with a CD4 count of <350 cells/mm3 resumed sex before healing, compared with 8.5% among HIV-positive men with a CD4 count of ≥350 cells/mm3 ( P = 0.052) and 7.8% ( P = 0.081) among HIV-negative men., Conclusion Inclusion of HIV-positive men with low CD4 counts in MMC services is not deleterious to postoperative wound healing. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data on malaria among hospitalized children in malaria endemic areas. We determined the prevalence, presentation and treatment outcomes of malaria and anemia among children in two hospitals in Rakai, Uganda. Methods: Children under five years hospitalized in Kalisizo hospital or Bikira health center in Rakai district, Uganda between May 2011 and May 2012 were enrolled and followed-up until discharge, death or referral. Data were collected on social-demographic characteristics, current and past illnesses and clinical signs and symptoms. Blood smears, hemoglobin (Hgb) levels and HIV testing were performed from finger/heel prick blood. The associations between malaria infection and other factors were estimated using log-binomial regression to estimate adjusted prevalence risk ratios (aPRR) and 95% confidence intervals (CIs), controlling for clustering at health facilities. Results: 2471 children were enrolled. The most common medical presentations were fever (96.2%), cough (61.7%), vomiting (44.2%), diarrhea (20.8%), and seizures (16.0%). The prevalence of malaria parasitemia was 54.6%. Children with malaria were more likely to present with a history of fever (aPRR 2.23; CI 1.18–4.24) and seizures (aPRR 1.12; CI 1.09–1.16). Confirmed malaria was significantly lower among girls than boys (aPRR 0.92; CI 0.91–0.93), HIV infected children (aPRR 0.60 CI 0.52–0.71), and children with diarrhea (aPRR 0.76; CI 0.65–0.90). The overall prevalence of anemia (Hgb<10 g/dl) was 56.3% and severe anemia (Hgb<6 g/dL) was 17.8%. Among children with severe anemia 76.8% had malaria parasitemia, of whom 93.1% received blood transfusion. Malaria associated mortality was 0.6%. Conclusion: There was a high prevalence of malaria parasitemia and anemia among inpatient children under five years. Malaria prevention is a priority in this population. [ABSTRACT FROM AUTHOR]

Male circumcision (MC) reduces high-risk human papillomavirus (HR-HPV) infection in female partners. We evaluated the intensity of HR-HPV viral DNA load in HIV-negative, HR-HPV-positive female partners of circumcised and uncircumcised men. HIV-negative men and their female partners were enrolled in randomized trials of MC in Rakai, Uganda. Vaginal swabs were tested for HR-HPV genotypes by Roche HPV Linear Array which provides a semi-quantitative measure of HPV DNA by the intensity of genotype-specific bands (graded:1-4). We assessed the effects of MC on female HR-HPV DNA load by comparing high intensity linear array bands (3-4) to low intensity bands (1-2) using an intention-to-treat analysis. Prevalence risk ratios (PRR) of high intensity bands in partners of intervention versus control arm men were estimated using log-binomial regression with robust variance. The trial included 335 women with male partners in the intervention arm and 340 in the control arm. At enrollment, the frequency of HR-HPV high intensity linear array bands was similar in both study arms. At 24 months follow-up, the prevalence of high intensity bands among women with detectable HR-HPV was significantly lower in partners of intervention arm (42.7%) than control arm men (55.1%, PRR = 0.78, 95%CI 0.65-0.94, p = 0.02), primarily among incident HR-HPV infections (PRR = 0.66, 95% CI 0.50-0.87, p = 0.003), but not persistent infections (PRR = 1.02, 95% CI 0.83-1.24). Genotypes with high HR-HPV band intensity were more likely to persist (adjHR = 1.27 95% CI 1.07-1.50), irrespective of male partner circumcision status. MC reduces HR-HPV DNA load in newly infected female partners. [ABSTRACT FROM AUTHOR]

Background. The association between human papillomavirus (HPV) infection and the risk of human immunodeficiency virus (HIV) seroconversion is unclear, and the genital cellular immunology has not been evaluated.Methods. A case-control analysis nested within a male circumcision trial was conducted. Cases consisted of 44 male HIV seroconverters, and controls were 787 males who were persistently negative for HIV. The Roche HPV Linear Array Genotype Test detected high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Generalized estimating equations logistic regression was used to estimate adjusted odds ratios (aORs) of HIV seroconversion. In addition, densities of CD1a+ dendritic cells, CD4+ T cells, and CD8+ T cells were measured using immunohistochemistry analysis in foreskins of 79 males randomly selected from participants in the circumcision trial.Results. HR-HPV or LR-HPV acquisition was not significantly associated with HIV seroconversion, after adjustment for sexual behaviors. However, HR-HPV and LR-HPV clearance was significantly associated with HIV seroconversion (aOR, 3.25 [95% confidence interval {CI}, 1.11–9.55] and 3.18 [95% CI, 1.14–8.90], respectively). The odds of HIV seroconversion increased with increasing number of HPV genotypes cleared (P < .001, by the test for trend). The median CD1a+ dendritic cell density in the foreskin epidermis was significantly higher among males who cleared HPV (72.0 cells/mm2 [interquartile range {IQR}, 29.4–138.3 cells/mm2]), compared with males who were persistently negative for HPV (32.1 cells/mm2 [IQR, 3.1–96.2 cells/mm2]; P = .047), and increased progressively with the number of HPV genotypes cleared (P = .05).Conclusions. HPV clearance was associated with subsequent HIV seroconversion and also with increased epidermal dendritic cell density, which potentially mediates HIV seroconversion. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: We conducted a retrospective population-based study to describe longitudinal patterns of prevalence, incidence, discontinuation, resumption, and durability of substantial HIV risk behaviors (SHR) for pre-exposure prophylaxis (PrEP) eligibility. Methods: The study was conducted among HIV-negative study participants aged 15–49 years who participated in survey rounds of the Rakai Community Cohort Study between August 2011 and June 2018. Substantial HIV risk was defined based on the Uganda national PrEP eligibility as reporting sexual intercourse with >1 partner of unknown HIV status, nonmarital sex without a condom, having genital ulcers, or having transactional sex. Resumption of SHR meant resuming of SHR after stopping SHR, whereas persistence of SHR meant SHR on >1 consecutive visit. We used generalized estimation equations with log-binomial regression models and robust variance to estimate survey-specific prevalence ratios; Generalized estimation equations with modified Poisson regression models and robust variance to estimate incidence ratios for incidence, discontinuation, and resumption of PrEP eligibility. Findings: Incidence of PrEP eligibility increased from 11.4/100 person-years (pys) in the first intersurvey period to 13.9/100 pys (adjusted incidence rate ratios = 1.28; 95%CI = 1.10–1.30) and declined to 12.6/100 pys (adjusted incidence rate ratios = 1.06; 95%CI = 0.98–1.15) in the second and third intersurvey periods, respectively. Discontinuation rates of SHR for PrEP eligibility were stable (ranging 34.9/100 pys–37.3/100 pys; P = 0.207), whereas resumption reduced from 25.0/100 pys to 14.5/100 pys (P < 0.001). PrEP eligibility episodes lasted a median time of 20 months (IQR = 10–51). Interpretation: Pre-exposure prophylaxis use should be tailored to the dynamic nature of PrEP eligibility. Preventive-effective adherence should be adopted for assessment of attrition in PrEP programs. [ABSTRACT FROM AUTHOR]

It has been hypothesized that increased HIV acquisition in uncircumcised men may relate to a more thinly keratinized inner foreskin. However, published data are contradictory and potentially confounded by medical indications for circumcision. We tested the hypothesis that the inner foreskin was more thinly keratinized than the outer foreskin using tissues from 19 healthy, HIV-uninfected men undergoing routine prophylactic circumcision in Rakai, Uganda. Sections from 3 foreskin anatomic sites (inner, outer, and frenar band) were snap-frozen separately. Two independent laboratories each separately stained, imaged, and measured keratin thicknesses in a blinded fashion. There was no significant difference in keratin thickness between the inner (mean = 14.67±7.48 μm) and outer (mean = 13.3±8.49 μm) foreskin, or between the inner foreskin and the frenar band (mean = 16.91±12.42 μm). While the frenar band showed the greatest intra-individual heterogeneity in keratin thickness, there was substantial inter-individual variation seen in all regions. Measurements made by the two laboratories showed high correlation (r = 0.741, 95% CI, 0.533-0.864). We conclude that, despite inter- and intra-individual variability, keratin thickness was similar in the inner and outer foreskin of healthy Ugandan men, and that reduced keratin thickness is not likely to make the inner foreskin more susceptible to HIV acquisition. [ABSTRACT FROM AUTHOR]

Methods. Uncircumcised human immunodeficiency virus (HIV)-negative men aged 15-49 years were randomized to immediate circumcision (intervention arm, 441 subjects) or delayed circumcision (control arm, 399 subjects). Human papillomavirus (HPV) was detected by Roche HPV Linear Array at enrollment, and at 6, 12, and 24 months. Incident high-risk HPV (HR-HPV) was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RRs) and 95% confidence intervals (CIs) of HR-HPV acquisition were estimated by Poisson multiple regression. Results. Enrollment characteristics were comparable between study groups. HR-HPV incidence was 19.7 cases per 100 person-years (PYs) in the intervention arm (70 cases per 355.8 PYs) and 29.4 cases per 100 PYs (125 cases per 424.8 PYs) in the control arm (RR, 0.67; 95% CI, 0.51-0.89; Pp.006). The incidence of multiple HRHPV infections was 6.7 cases per 100 PYs in the intervention arm and 14.8 cases per 100 PYs in the control arm (RR, 0.45; 95% CI, 0.28-0.73), but there was no significant effect on single infections (RR, 0.89; 95% CI, 0.60- 1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of preexisting HR-HPV infections was 215.8 cases per 100 PYs (205 cases per 95 PYs) in the intervention arm and 159.1 cases per 100 PYs (255 cases per 160.25 PYs) in the control arm (adjusted RR, 1.39; 95% CI, 1.17-1.64). Conclusions. Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men. Trial Registration. ClinicalTrials.gov identifier: NCT00425984. [ABSTRACT FROM AUTHOR]

In Rakai, Uganda, human immunodeficiency virus (HIV)-positive men were randomized to undergo either immediate circumcision (intervention arm) or delayed circumcision (control arm). Penile swab samples were assayed for high-risk human papillomavirus (HR-HPV) by Roche HPV Linear Array at enrollment and at 24 months (intervention arm, 103 subjects; control arm, 107 subjects). Rate ratios (RRs) of HR-HPV were estimated by Poisson regression. At 24 months, HR-HPV prevalence was found in 57 (55.3%) of 103 subjects in the intervention arm and in 77 (71.7%) of 107 subjects in the control arm (RR, 0.77; 95% confidence interval [CI], 0.62-0.97). Multiple HR-HPV infections were found in 19 (22.4%) of 85 subjects in the intervention arm and in 45 (42.5%) of 106 subjects in the control arm (RR, 0.53; 95% CI, 0.33-0.83). New HR-HPV genotypes were acquired by 34 (42.0%) of 81 subjects in the intervention arm and by 53 (57.0%) 85 subjects in the control arm (RR, 0.74; 95% CI, 0.54-1.01; Pp.06). Multiple new HR-HPV genotypes were acquired by 8 (9.9%) of 81 subjects in the intervention arm and by 23 (24.7%) of 93 subjects in the control arm (RR, 0.40; 95% CI, 0.19-0.84; Pp.01). Circumcision did not affect the acquisition of single HR-HPV infections (RR, 1.00; 95% CI 0.65-1.53) or clearance of HR-HPV infections (RR, 1.09; 95% CI 0.94-1.27). Circumcision of HIV-positive men reduced the prevalence and incidence of multiple HR-HPV infections. Trial Registration. ClinicalTrials.gov identifier: NCT00124878. [ABSTRACT FROM AUTHOR]

Little is known about risk factors for incident herpes simplex virus type 2 (HSV-2) infection among men in Africa. In a trial in Rakai, Uganda, 6396 men aged 15-49 years were evaluated for serological evidence of HSV-2, human immunodeficiency virus (HIV), and syphilis infections at enrollment and at 6, 12, and 24 months. The prevalence of HSV-2 infection was 33.76%, and the incidence was 4.90 cases per 100 person-years. HSV-2 incidence increased with alcohol use with sexual intercourse (adjusted incidence rate ratio [adjIRR], 1.92 [95% confidence interval {CI}, 1.46 -2.53]), decreased with consistent condom use (adjIRR, 0.56 [95% CI, 0.36-0.89]) and male circumcision (adjIRR, 0.70 [95% CI, 0.55- 0.91]), and was not significantly affected by enrollment HIV status. Education on modifiable behavioral changes may reduce the acquisition of HSV-2. (ClinicalTrials.gov identifiers: NCT00425984 and NCT00124878.) [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. Methods. We determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4+ cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4+ cell count of ⩽250 cells/mm³) and to AIDS-associated death. Results. A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D (6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years; P = .022). Relative to subtype A, adjusted HRs of progression to AIDS were 2.13 [95% confidence interval {CI}, 1.10-4.11] for subtype D, 2.16 [95% CI, 1.05-4.45] for recombinant subtypes, and 4.40 [95% CI, 1.71-11.31 for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR, 5.65; 95% CI, 1.37-23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27-46.3), compared with subtype A. Conclusions. HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression. [ABSTRACT FROM AUTHOR]

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands OBJECTIVE To investigate the relationship between adult male circumcision and sexual satisfaction and function in men, as observational studies on the effect of adult male circumcision on sexual satisfaction show conflicting results. SUBJECTS AND METHODS We investigated self-reported sexual satisfaction and function among men enrolled in a randomized trial of male circumcision for human immunodeficiency virus (HIV) prevention conducted in Rakai, Uganda. In all, 4456 sexually experienced HIV-negative males aged 15–49 years were enrolled; 2210 were randomized to receive immediate circumcision (intervention arm) and 2246 to circumcision delayed for 24 months (control arm). Men were followed up at 6, 12 and 24 months, and information on sexual desire, satisfaction and erectile dysfunction was collected. These variables were compared between the study arms and over time within the study arms, using chi-square or Fisher’s exact tests. The trial registration number is NCT00425984. RESULTS There were no differences between the study arms at enrolment and problems with sexual satisfaction and function were reported by <2% of participants in both study arms at all time points. At 6 months, no difficulty with penetration was reported by 98.6% of circumcised men and 99.4% of controls ( P = 0.02), and no pain on intercourse was reported by 99.4% circumcised and 98.8% of uncircumcised men ( P = 0.05). There were no differences between the study arms in penetration or dyspareunia at later visits. Sexual satisfaction increased from 98.0% at enrolment to 99.9% at 2 years among the controls ( P < 0.001), but there was no trend in satisfaction among circumcised men (enrolment 98.5%, 2 years 98.4%, P = 0.8). CONCLUSION Adult male circumcision does not adversely affect sexual satisfaction or clinically significant function in men. [ABSTRACT FROM AUTHOR]

The article presents a study on the mortality rates in human immunodeficiency virus (HIV)-1-infected and uninfected infants born to HIV-infected and uninfected mothers in rural Uganda. The study used the data from a prospective study in rural Rakai District. The results of the study was discussed and concluded that more than half of HIV-infected infants died at less than two years of age. In addition, it suggests that antiretroviral therapy may need to be initiated earlier in infected patients.

In developing countries, Mother-to-Child Transmission-Plus programmes propose to identify lifelong antiretroviral therapy (ART)-eligible women during antenatal care. Identification using AIDS-related symptoms is the most feasible screening procedure in resource-limited settings. It is not known if symptomatology in pregnant women is correlated with clinical criteria for ART initiation based on CD4+ cell count or HIV-1 viral load. In this population of HIV-positive pregnant women from Rakai District, Uganda, 8–23% were eligible for treatment by CD4+ cell count criteria, and <1% met WHO staging criteria for AIDS. Using one or more symptoms to predict CD4+ cell count <350 cells/mm3, sensitivity was 100%, specificity 11%, positive predictive value (PPV) 25%, and negative predictive value (NPV) 100%. When using one or more symptoms to predict viral load ≥100,000 cps/mL, sensitivity was 100%, specificity 10%, PPV 6%, and NPV 100%. Initiation of treatment based on self-reported symptoms will over-treat because the majority of pregnant women with symptoms would not be eligible for treatment under current guidelines, but asymptomatic pregnant women are unlikely to require ART. [ABSTRACT FROM AUTHOR]