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Introduction: Voluntary medical male circumcision (VMMC) reduces the risk of heterosexual acquisition of HIV by 50%–60%. The Uganda Ministry of Health recommends abstinence of sex for 42 days after VMMC to allow complete wound healing. However, some men resume sex early before the recommended period. We estimated trends in prevalence and risk factors of early sex resumption (ESR) among VMMC clients in Rakai, Uganda, from 2013–2020. Methods: Data from the Rakai Community Cohort Study (RCCS), a cross-sectional study, were analyzed. Data included consenting males aged 15–49 years in RCCS who self-reported having received VMMC between the period of 2013 to 2020. ESR prevalence and associated risk factors were assessed using modified Poisson regression to estimate adjusted prevalence ratios (aPR). Results: Overall, 1,832 participants were included in this study. ESR decreased from 45.1% in 2013 to 14.9% in 2020 (p<0.001). Across the first three surveys, ESR prevalence was consistently higher among the married participants than the never married participants, aPR = 1.83, 95% CI: [1.30,2.57]; aPR = 2.46, 95% CI: [1.50,4.06]; aPR = 2.22, 95% CI: [1.22,4.03]. ESR prevalence was higher among participants who reported to have more than one sexual partner than participants with one partner, aPR = 1.59, 95% CI: [1.16,2.20]. In the fourth survey from 2018–2020, ESR prevalence was significantly higher among participants with primary education than participants with post-primary, aPR = 2.38, 95% CI: [1.31, 4.30]. However, ESR prevalence was lower among participants aged at least 45 years than participants aged 15–19 years, aPR = 0.0, 95% CI: [1.86e-07, 2.69e-06]. Overall, participants who reported primary school as their highest level of education reported ESR more often than those with post-primary education aPR = 2.38, 95% CI: [1.31, 4.30]. Occupation and known HIV status were not associated with ESR. Conclusions: Self-reported ESR after VMMC declined between 2013 and 2020. Targeted efforts for counseling focusing on married men, men who had multiple sex partners, and men with lower levels of education may decrease ESR. [ABSTRACT FROM AUTHOR]

Background: Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence and lockdown and a severe lake flooding event, both of which occurred in 2020. Methods: We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda. The data were collected both prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence and a severe flooding event. Households impacted by flooding were identified via drone data and through consulting village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-differences statistical modeling approach. Findings: A total of 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. After the COVID-19 pandemic and lockdown, we observed a decline in HIV-associated risk behaviors: transactional sex declined from 29.4% to 24.8% (p = 0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p = 0.021). ART coverage increased from 91.6% to 97.2% (p<0.001). There was 17% decline in transactional sex (aPR = 0.83, 95% CI: 0.75–0.92) and 28% decline in the overall HIV risk score (aPR = 0.83, 95% CI: 0.75–0.92) among HIV-seronegative participants. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes when comparing those affected by floods to those not affected by floods, in the periods before and after COVID-19, based on difference-in-differences analyses. Interpretation: Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and/or population resilience. Understanding exactly what HIV programs and personal or community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events. [ABSTRACT FROM AUTHOR]

Background: Globally, the prevalence of chronic non-communicable diseases (C-NCDs) and occurrence of multi-morbidity specifically, has been increasing and will continue to rise as life expectancy increases. The burden of mental health disorders has also been rising globally. In sub-Saharan Africa (SSA), literature on these health issues, which are interrelated, is scarce. This study assesses the prevalence of C-NCDs, and depressive and anxiety symptomology and examines the relationship between these issues among a sample of older adults in Uganda. Methods: Between 2021–2022, 604 consenting adults aged 35 years and older were surveyed on a broad range of health issues for the ongoing AMBSO Population Health Surveillance (APHS) cohort study in Wakiso district. Descriptive analyses were performed to characterize the burden of C-NCDs (e.g. diabetes, hypertension), depression (PHQ-9 using a cutoff of <5 scores for minimal/no and 5+ for mild to severe symptomology) and anxiety (GAD-7 using a cutoff of 5+ scores for mild to severe symptomology). Bivariate analysis and multivariable logistic regression models were built using STATA software version 16.0 to examine associations between mental health disorders and having at least one C-NCD. Our exposures of interest were depressive and anxiety symptoms and our outcomes of interest was presence of C-NCDs. Results: Majority of participants were females (63.6%), median age was 46 (IQR: 39–54). Any C-NCDs prevalence was 18.7%, while 18.9% and 11.4%, had screening scores indicative of depressive and anxiety symptomology, respectively. Three percent (3.2%) had PHQ-9 scores indicative of moderate to severe depressive symptomology. In models adjusted for sociodemographic characteristics, there was 12% increased odds of suffering from C-NCDs for every unit increase in PHQ-9 score (AOR = 1.12, 95% CI: 1.10–1.20). Participants with any anxiety symptoms had 2.1 greater odds of suffering from C-NCD compared to those who did not have anxiety symptoms (AOR = 2.10, 95% CI: 1.21–3.70). Conclusion: C-NCDs were prevalent in older adults, particularly among those experiencing mental health symptoms. Screening for C-NCDs and mental health disorders should be integrated into routine health care for older adults in the country. Early screening and identification of these health issues through primary health care could significantly reduce the public health burden attributable to mental health disorders and the incidence of multi-morbidity in Uganda. [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]

Background The objective of the study was to compare rates of adverse events (AEs) related to male circumcision (MQ in HIV-positive and HIV-negative men in order to provide guidance for MC programs that may provide services to HIV-infected and uninfected men. Methods and Findings A total of 2,326 HIV-negative and 420 HIV-positive men (World Health Organization [WHO] stage I or II and CD4 counts > 350 cells/m[m.sup.3]) were circumcised in two separate but procedurally identical trials of MC for HIV and/or sexually transmitted infection prevention in rural Rakai, Uganda. Participants were followed at 1-2 d and 5-9 d, and at 4-6 wk, to assess surgery-related AEs, wound healing, and resumption of intercourse. AE risks and wound healing were compared in HIV-positive and HIV-negative men. Adjusted odds ratios (AdjORs) were estimated by multiple logistic regression, adjusting for baseline characteristics and post-operative resumption of sex. At enrollment, HIV-positive men were older, more likely to be married, reported more sexual partners, less condom use, and higher rates of sexually transmitted disease symptoms than HIV-negative men. Risks of moderate or severe AEs were 3.1/100 and 3.5/100 in HIV-positive and HIV-negative participants, respectively (AdjOR 0.91, 95% confidence interval [CI] 0.47-1.74). Infections were the most common AEs (2.6/100 in HIV-positive versus 3.0/100 in HIV-negative men). Risks of other complications were similar in the two groups. The proportion with completed healing by 6 wk postsurgery was 92.7% in HIV-positive men and 95.8% in HIV-negative men (p = 0.007). AEs were more common in men who resumed intercourse before wound healing compared to those who waited (AdjOR 1.56,95% Cl 1.05-2.33). Conclusions Overall, the safety of MC was comparable in asymptornatic HIV-positive and HIV-negative men, although healing was somewhat slower among the HIV infected. All men should be strongly counseled to refrain from intercourse until full wound healing is achieved. Trial registration: http://www.ClinicalTrials.gov; for HIV-negative men #NCT00425984 and for HIV-positive men, #NCT00124878. The Editors'Summory of this article follows the references., Introduction Three randomized trials have shown that male circumcision (MC) reduces the risk of male HIV acquisition in men by 50%-60% [1-3]. This finding suggests that the procedure may be [...]

Introduction: Uganda confirmed its first COVID-19 case in March 2020, leading to country-wide closures and a stay-at-home order. Infectious disease pandemics can overwhelm adaptive coping capacity (e.g., general self-efficacy and resilience) and increase the risk for mental distress. For individuals experiencing intimate partner violence (IPV) and cohabitating with a perpetrator, stay-at-home orders can also increase risk of violence, which can further exacerbate mental distress. The present study explores women's perceived self-efficacy and resilient coping, mental health outcomes (depression and COVID-19 related anxiety), hazardous alcohol use and IPV in the context of Uganda's national 2020 lockdown. Methods: A phone-based survey was undertaken from June-August of 2020 in Wakiso District, Uganda. The study sample consisted of Africa Medical and Behavioral Sciences Organization (AMBSO) Population Health Surveillance (APHS) study participants who agreed to be contacted for future research. The analytic sample was restricted to women aged 13–80 years. Bivariate analysis and multivariable models explored associations between experiences of IPV and measures of adaptive coping, mental health and alcohol use. Results: A total of 556 women aged 13–79 years (mean age of 33.4 years) participated. Over half (55%) were currently married. The majority (60%) reported a decrease in alcohol use during the lockdown. Nearly half of the sample were experiencing physical or verbal IPV and reported an increase in violence during the lockdown. In adjusted analysis, alcohol use was associated with four times greater odds of recent physical IPV (aOR 4.06, 95% CI = 1.65–10.02, p = 0.0024), while participants had lower odds of experiencing any form of IPV as general self-efficacy increased (aOR 0.95, 95% CI = 0.91–0.99, p = 0.0308). Conclusion: Lockdown measures in Uganda may have mitigated increased alcohol consumption. IPV was exacerbated during lockdown; more than 2 in 5 IPV victims experienced increased physical or verbal violence. Development of programming and policies aimed at mitigating women's risk of IPV during future lockdowns are needed. [ABSTRACT FROM AUTHOR]

Background A randomized trial of voluntary medical male circumcision (MC) of HIV--infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC. Methods and Findings HIV shedding was evaluated among 223 HIV--infected men (183 self--reported not receiving antiretroviral therapy [ART], 11 self--reported receiving ART and had a detectable plasma viral load [VL], and 29 self--reported receiving ART and had an undetectable plasma VL [ 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART--induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow--up for those who were not on ART at enrollment. Conclusion Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC., Introduction Three randomized trials demonstrated that voluntary medical male circumcision, hereafter referred to as male circumcision (MC), significantly decreases heterosexual HIV acquisition in men by 50%-60% [1-3]. MC of HIV-negative [...]

Introduction: Antenatal alcohol use is linked to adverse maternal and neonatal outcomes. Uganda has one of the highest rates of alcohol use in sub-Saharan Africa, but the prevalence of antenatal alcohol use has not been reported in the Rakai region. Methods: We used cross-sectional data from pregnant women in the Rakai Community Cohort Study between March 2017 and September 2018. Using bivariate and multivariable analyses, we assessed associations between self-reported antenatal alcohol use and sociodemographic characteristics, intimate partner violence (IPV), and HIV status. Results: Among 960 pregnant women, the median age was 26 years, 35% experienced IPV in the past 12 months, 13% were living with HIV, and 33% reported alcohol use during their current pregnancy. After adjusting for marital status, education, smoking, and HIV status; Catholic religion (AOR: 3.54; 95% CI: 1.89–6.64; compared to other), bar/restaurant work (AOR: 2.40; 95% CI: 1.17–4.92; compared to agriculture), >one sex partner in past year (AOR: 1.92; 95% CI: 1.17–3.16), a partner that drank before sex in past year (AOR: 2.01; 95% CI: 1.48–2.74), and past year IPV (AOR: 1.55; 95% CI: 1.14–2.11) were associated with antenatal alcohol use. Conclusion: We found that alcohol use during pregnancy was common and associated with religion, occupation, higher numbers of past year sex partners, having a partner who drank before sex in the past 12 months, and IPV experience. More research is needed to understand the quantity, frequency, and timing of antenatal alcohol use; and potential impacts on neonates; and to identify services that are acceptable and effective among pregnant women. [ABSTRACT FROM AUTHOR]

Introduction: Uganda has one of the highest rates of alcohol use in sub-Saharan Africa but prevalence and correlates of drinking are undocumented in the Rakai region, one of the earliest epicenters of the HIV/AIDS epidemic in East Africa. Methods: We analyzed cross-sectional data from 18,700 persons (8,690 men, 10,010 women) aged 15–49 years, living in agrarian, trading and fishing communities and participating in the Rakai Community Cohort Study (RCCS) between March 2015 and September 2016. Logistic regression models assessed associations between past year alcohol use and sociodemographic characteristics, other drug use and HIV status, controlling for age, religion, education, occupation, marital status, and household socioeconomic status. Results: Past year alcohol prevalence was 45%. Odds of drinking were significantly higher in men (versus women) and fishing communities (versus agrarian areas). Odds of drinking increased with age, previous (versus current) marriage and past year drug use. By occupation, highest odds of drinking were among fishermen and (in women) bar/restaurant workers. Alcohol-related consequences were more commonly reported by male (vs. females) drinkers, among whom up to 35% reported alcohol dependence symptoms (e.g., unsteady gait). HIV status was strongly associated with alcohol use in unadjusted but not adjusted models. Conclusions: Alcohol use differed by gender, community type and occupation. Being male, living in a fishing community and working as a fisherman or restaurant/bar worker (among women) were associated with higher odds of drinking. Alcohol reduction programs should be implemented in Uganda's fishing communities and among people working in high risk occupations (e.g., fishermen and restaurant/bar workers). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Male circumcision (MC) reduces acquisition of HIV-1 in heterosexual men by at least 60%, but the biological mechanism for this protection is incompletely understood. Previous studies have shown that a larger foreskin size, increased abundance of anaerobic bacteria in the sub-preputial space, and higher levels of pro-inflammatory cytokines on the penis are all prospectively associated with risk of HIV-1 acquisition. Since coverage of the glans on the non-erect penis is dependent on foreskin size, a larger foreskin could result in a less aerobic environment that might preferentially support anaerobic bacterial growth and induce inflammation. We therefore assessed the relationship between foreskin size, penile microbiome composition and local inflammation. Methods: This is a retrospective, cross-sectional analysis of 82 HIV-uninfected men who participated in a randomized trial of MC for HIV-1 prevention in Rakai, Uganda between 2003–2006. Sub-preputial swabs were collected prior to MC and assessed for cytokines (multiplexed immunosorbent assay) and bacterial load (qPCR) and taxon abundance (sequencing). Foreskin size was measured immediately after MC. Results: Foreskin surface area did not correlate with total bacterial load (rho = 0.05) nor the abundance of key taxa of bacteria previously associated with HIV-1 risk (rho = 0.04–0.25). Foreskin surface area also did not correlate with sub-preputial cytokine concentrations previously associated with HIV-1 risk (IL-8 rho = 0.05). Conclusions: Larger foreskin size is not associated with either increased penile anaerobes or pro-inflammatory cytokines. These data suggest that foreskin size does not increase HIV-1 risk through changes in penile microbiome composition or penile inflammation. [ABSTRACT FROM AUTHOR]

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. [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]

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: In Kasensero fishing community, home of the first recorded case of HIV in Uganda, HIV transmission is still very high with an incidence of 4.3 and 3.1 per 100 person-years in women and men, respectively, and an HIV prevalence of 44%, reaching up to 74% among female sex workers. We explored drivers for the high HIV transmission at Kasensero from the perspective of fishermen and other community members to inform future policy and preventive interventions. Methods: 20 in-depth interviews including both HIV positive and HIV negative respondents, and 12 focus-group discussions involving a total of 92 respondents from the Kasensero fishing community were conducted during April-September 2014. Content analysis was performed to identify recurrent themes. Results: The socio-economic risk factors for high HIV transmission in Kasensero fishing community cited were multiple and cross-cutting and categorized into the following themes: power of money, risk denial, environmental triggers and a predisposing lifestyle and alcoholism and drug abuse. Others were: peer pressure, poor housing and the search for financial support for both the men and women which made them vulnerable to HIV exposure and or risk behavior. Conclusions: There is a need for context specific combination prevention interventions in Kasensero that includes the fisher folk and other influential community leaders. Such groups could be empowered with the knowledge and social mobilization skills to fight the negative and risky behaviors, perceptions, beliefs, misconceptions and submission attitudes to fate that exposes the community to high HIV transmission. There is also need for government/partners to ensure effective policy implementation, life jackets for all fishermen, improve the poor housing at the community so as to reduce overcrowding and other housing related predispositions to high HIV rates at the community. Work place AIDS-competence teams have been successfully used to address high HIV transmission in similar settings. [ABSTRACT FROM AUTHOR]

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. [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]

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]

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]

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]

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-odifyin 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 (x2 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 21.2 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. [ABSTRACT FROM AUTHOR]

Background: Data comparing survival of formula-fed to breast-fed infants in programmatic settings are limited. We compared mortality and HIV-free of breast and formula-fed infants born to HIV-positive mothers in a program in rural, Rakai District Uganda. Methodology/Principal Findings: One hundred eighty two infants born to HIV-positive mothers were followed at one, six and twelve months postpartum. Mothers were given infant-feeding counseling and allowed to make informed choices as to whether to formula-feed or breast-feed. Eligible mothers and infants received antiretroviral therapy (ART) if indicated. Mothers and their newborns received prophylaxis for prevention of mother-to-child HIV transmission (pMTCT) if they were not receiving ART. Infant HIV infection was detected by PCR (Roche Amplicor 1.5) during the follow-up visits. Kaplan Meier time-to-event methods were used to compare mortality and HIV-free survival. The adjusted hazard ratio (Adjusted HR) of infant HIV-free survival was estimated by Cox regression. Seventy-five infants (41%) were formula-fed while 107 (59%) were breast-fed. Exclusive breast-feeding was practiced by only 25% of breast-feeding women at one month postpartum. The cumulative 12-month probability of infant mortality was 18% (95% CI = 11%-29%) among the formula-fed compared to 3% (95% CI = 1%-9%) among the breast-fed infants (unadjusted hazard ratio (HR) = 6.1(95% CI = 1.7-21.4, P-value,0.01). There were no statistically significant differentials in HIV-free survival by feeding choice (86% in the formula-fed compared to 96% in breast-fed group (Adjusted RH = 2.8[95%CI = 0.67-11.7, P-value = 0.16] Conclusions/Significance: Formula-feeding was associated with a higher risk of infant mortality than breastfeeding in this rural population. Our findings suggest that formula-feeding should be discouraged in similar African settings. [ABSTRACT FROM AUTHOR]

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: Drs. Wawer and Gray are paid consultants to the Rakai Health Sciences Program and serve on its Board of Directors. These arrangements have been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Modern contraceptive use has increased globally, but unmet needs persist in low- and middle-income countries. This study in Uganda aimed to examine the prevalence and factors influencing the use of short-acting reversible contraceptives (SARC) like pills and long-term methods such as intrauterine devices. Limited evidence exists on the use of SARC and long-term methods in Uganda. Data from the Africa Medical and Behavioural Sciences Organization (AMBSO) Population Health Surveillance (APHS) in Hoima and Wakiso districts were analysed. Among the 1642 women aged 15-49 years, the prevalence of modern contraceptive use was 30% for SARC, and 18% for long-term method. Women with formal education were three times more likely to use long-term methods than those without formal education, relative risk ratios (RRR), 3.1-3.4, (95%CI 1.2-8.2). Joint decision-making for contraceptive use increased SARC usage, RRR 1.4 (95%CI 1.1-1.8). Urbanization played a role, with women in more urbanized Wakiso district less likely to use any modern contraception, RRR 0.6-0.7 (95%CI 0.5-0.9) compared to those living in the less urbanized Hoima. About half of the women in the study used modern contraceptives and the use of SARC was almost twice that of long-term methods. Increased access to contraception education for all women of reproductive age could significantly improve the use of long-term methods which offer more reliable protection against unintended pregnancies. The findings shed light on the need to strengthen both general and sexuality education to girls and women and to tailor contraception access for all in need, for mobile semi-urban as well as rural women. Well-informed strategies that engage young men and male partners in informed decision-making for contraceptive use could enhance progress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Arunda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Understanding treatment-seeking behavior is critical to the treatment and control of sexually transmitted infections (STIs), yet current data on STI treatment seeking in low-resource settings is rare. This population-based study aimed to describe STI treatment-seeking behavior and identify factors associated with seeking treatment at a clinic among adults with STI-related symptoms in rural Uganda. The STI prevalence study (STIPS) conducted a survey and STI testing among all consenting adults aged 18-49 in two communities in rural south-central Uganda. Of 1,825 participants, 962 individuals self-reported STI symptoms in the past six months; we present descriptive data on treatment seeking and STI prevalence among these individuals. We used multivariable Poisson regressions with robust variance to determine the sociodemographic and symptom-related factors independently associated with seeking STI treatment at a clinic and assessed the association with previous clinic treatment seeking and current STI diagnosis. Forty-three percent of adults who reported STI-related symptoms in the past six months said they did not seek any treatment. Among those who did, 58% sought treatment at a private clinic, 28% at a government clinic, 9% at a pharmacy/drug store, 3% at a traditional healer, 2% at a market/shop, and 5% at another location. Among both males and females, having multiple STI related symptoms was positively associated with clinic treatment seeking (males = PRR: 1.73, 95%CI: 1.36-2.21; females = PR: 1.41, 95%CI: 1.12-1.78). Approximately one-third of males and females who reported previously seeking clinic treatment for their symptoms were diagnosed with a curable STI at the time of the survey. In this setting, nearly half of adults with STI-related symptoms are not seeking clinical care and many who report having sought treatment for recent STI symptoms have curable STIs. Future studies should explore barriers to care-seeking and strategies to improve STI services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ogale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Obesity is a rapidly growing global health challenge, but there are few population-level studies from non-urban settings in sub-Saharan Africa. We evaluated the prevalence of overweight (body mass index (BMI)>25 kg/m2), obesity (BMI>30 kg/m2), and associated factors using data from May 2018 to November 2020 from the Rakai Community Cohort Study, a population-based cohort of residents aged 15 to 49 living in forty-one fishing, trading, and agrarian communities in South Central Uganda. Modified Poisson regression was used to estimate adjusted prevalence risk ratios (PRR) and 95% confidence intervals (CI) in 18,079 participants. The overall mean BMI was 22.9 kg/m2. Mean BMI was 21.5 kg/m2 and 24.1 kg/m2 for males and females, respectively. The prevalence of overweight and obesity were 22.8% and 6.2%, respectively. Females had a higher probability of overweight/obesity (PRR: 4.11, CI: 2.98-5.68) than males. For female participants, increasing age, higher socioeconomic status, residing in a trading or fishing community (PRR: 1.25, CI 1.16-1.35 and PRR: 1.17, CI 1.10-1.25, respectively), being currently or previously married (PRR: 1.22, CI 1.07-1.40 and PRR: 1.16, CI 1.01-1.34, respectively), working in a bar/restaurant (PRR: 1.29, CI 1.17-1.45), trading/shopkeeping (PRR: 1.38, CI 1.29-1.48), and reporting alcohol use in the last year (PRR: 1.21, CI 1.10-1.33) were risk factors for overweight/obese. For male participants, increasing age, higher socioeconomic status, being currently married (PRR: 1.94, CI 1.50-2.50), residing in a fishing community (PRR: 1.68, CI 1.40-2.02), working in a bar/restaurant (PRR: 2.20, CI 1.10-4.40), trading/shopkeeping (PRR: 1.75, CI 1.45-2.11), or fishing (PRR: 1.32, CI 1.03-1.69) increased the probability of overweight/obesity. Non-Muslim participants, male smokers, and HIV-positive females had a lower probability of overweight/obese. The prevalence of overweight/obesity in non-urban Ugandans is substantial. Targeted interventions to high-risk subgroups in this population are needed., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2022 Ayoola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)