Ronald Moses Galiwango

Background: Laboratory testing is critical for diagnosis and treatment management for people with HIV, but is costly. When HIV resources are constrained, even before recent disruptions in US funding for the global HIV response, user fees have been used for cost recovery. We describe availability and charging of user fees for routine HIV laboratory testing globally. Methods: Routine test availability and charging of user fees were examined via an HIV clinic survey conducted September 2020–March 2021; responses reflected clinical practices in 2019. HIV clinics came from 42 low-, middle-, and high-income countries from the International epidemiology Databases to Evaluate AIDS (IeDEA) global research consortium. Results: Across 199 clinics, on-site test availability was generally limited, reflecting constraints in routine test availability across health conditions more broadly. Over 90% of clinics did not report charging of user fees. A higher percentage reporting user fees were from middle-income countries and from countries receiving Global Fund or PEPFAR country support, which may reflect settings with ongoing health funding gaps. Conclusions: Availability and user fees for essential HIV-related laboratory tests were limited in 2019. Monitoring user fees may provide insights about how national health systems are responding to steep reductions in global donor funding.

Specific anaerobic species within the penile microbiome – Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) – have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells.The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-/CD4+/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density).Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption.

SUMMARY: Background: Novel HIV prevention interventions such as long-acting pre-exposure prophylaxis (PrEP) could substantially reduce HIV transmission in Africa. However, efficient implementation in high-prevalence settings where incidence has declined requires an understanding of the contemporary dynamics driving new infections. Methods: We identified incident HIV cases from a longitudinal, population-based cohort in Uganda. We individually matched cases to HIV-negative controls; traced and enrolled reported sexual partners; and enrolled female sex workers (FSWs) from reported venues. Conditional logistic regression, transmission modeling, and phylogenetics were used to characterize transmission networks. Findings: From 2021-2024, 38,899 HIV tests among 22,255 people identified 187 people with incident infections (47.6% male); 164 (88%) were enrolled and matched to 164 HIV-negative controls. Overall, 593 non-sex-worker partners (371 enrolled,62.6%), 146 FSW partners (21 enrolled,14.4%), and 28 venues (208 FSWs enrolled) were reported. Incident infection was most strongly predicted by partnership with a FSW (odds ratio:15.5; 95%CI:3.7-64.8), identified in 43.0% of male cases versus 6.3% of controls. Men with FSW partners had larger sexual networks than men without (median:6 vs 2 partners), and 91.2% of men with FSW partners also had non-sex-worker partners. Transmission modeling attributed 34.4% (95%CI:31.5-36.8%) of all male infections and 80.0% (95%CI:73.2-84.4%) of infections among male clients to sex with FSWs. Oral PrEP use among HIV-negative partners of incident cases was low (8.9% in women; 2.1% in men). Interpretation: Men with FSW partners accounted for a substantial share of incident HIV infections and had markedly higher odds of infection than men without such partnerships. Together with the high potential for onward transmission within male client networks, these findings suggest that inclusion of male clients in long-acting HIV prevention strategies could be highly efficient and impactful. Funding: National Institutes of Health, United States; Gates Foundation; National Health and Medical Research Council, Australia

Background: Data on the population-scale impact of dolutegravir (DTG)-based HIV regimens in sub-Saharan Africa are extremely limited. We used data from a surveillance cohort in southern Uganda to assess viral suppression and antiretroviral (ART) resistance over 10-years alongside DTG scale-up. Methods: Consenting participants in the population-based Rakai Community Cohort Study between August 2011 and March 2023 aged 15–49 completed questionnaires and provided samples for HIV testing, viral load quantification, and viral deep-sequencing. We collected data on DTG utilization at HIV care clinics. We estimated the prevalence of HIV suppression and ART resistance using robust Poisson regression. Bayesian logistic regression quantified associations between resistance and individual-level suppression across surveys. Results: Among 8781 people with HIV (PWH), suppression increased from 57.1% (2014, 95% confidence interval [CI], 55.4%–58.8%) to 90.3% (2022, 95% CI, 89.2%–91.4%). By 2020 84.4% (95% CI, 83.7%–85.2%) and 64.6% (95% CI, 63.9%–65.3%) of men and women on ART were on DTG. Among treatment-experienced viremic PWH, any intermediate/high resistance decreased from 51.1% (95% CI, 40.7%–64.2%, 2014) to 27.9% (95% CI, 21.3%–36.5%, 2022). Two of 258 (0.8%) 2022 participants harbored intermediate/high-level DTG resistance (inQ148R, inE138K, and inG140A). inS153Y (2-fold INSTI resistance) was observed in 23/306 (7.5%) of viremic individuals, with evidence of transmission. By 2022, NNRTI/NRTI resistance was not associated with a reduction in individual-level suppression (risk ratios: 1.15, 95% HPD: 0.93–1.39; 1.14, 0.86–1.42). Conclusions: Viral suppression increased during the DTG transition with minimal emerging intermediate/high-level resistance. Falling resistance among treatment-experienced PWH underscores the role of ART adherence in reducing viremia. The emergence of inS153Y justifies continued surveillance.

Objective: Partner-level sexually transmitted infection (STI) data from eastern Africa are rare, despite high STI burden. To address this gap, we examined STI prevalence and clustering among cohabiting couples in two high HIV-burden Ugandan communities, representing the largest population-based, couple-level STI study in the region. Methods: We analysed data from the Sexually Transmitted Infection Prevalence Study (STIPS), a cross-sectional, population-based study in southern Uganda which tested participants for chlamydia, gonorrhoea, trichomonas, syphilis, high-titre syphilis and herpes simplex virus-2 (HSV-2). We restricted the present analysis to STIPS participants in a cohabiting sexual relationship. Poisson regression with robust standard errors was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs) of all STIs by partner’s infection status. Results: Among 423 cohabiting heterosexual couples, at least one partner tested positive for a curable STI (chlamydia, gonorrhoea, trichomonas or high-titre syphilis) in 37% of couples. STIs were strongly clustered within partner dyads. For example, female participants with male partners with gonorrhoea had increased prevalence of not only gonorrhoea (PR 10.4, 95% CI 6.4 to 16.8) but also HIV (PR 2.2, 95% CI 1.5 to 3.2), chlamydia (PR 2.5, 95% CI 1.1 to 5.7), trichomonas (PR 2.4, 95% CI 1.2 to 4.7) and HSV-2 (PR 1.3, 95% CI 1.1 to 1.7). Conclusion: Partners of individuals with an STI are more likely to have a curable STI, which may be the same or may be a different pathogen; broad screening of partners could be essential to curbing transmission and preventing reinfection. Comprehensive couple-based approaches, including partner notification, treatment and counselling strategies, are critical for reducing STI disease burden.

Objectives Migration is associated with increased risk of HIV infection in Africa, but evidence about non-HIV sexually transmitted infection (STI) burden among African migrants is limited. Methods We used data from the Sexually Transmitted Infection Prevalence Study, a cross-sectional population-based study of chlamydia, gonorrhoea, trichomoniasis, syphilis and herpes simplex virus type 2 prevalence in southern Uganda, to compare STI prevalence between adults aged 18 and 49 years with and without a recent history of migration. Migration status was determined using household census data, with a recent migration history defined as having moved into one’s community of current residence within the last ~18 months. Unadjusted and adjusted modified Poisson regression models were used to compare individual STI prevalence risk by recent migration status with associations reported as adjusted prevalence risk ratios (adjPRRs) with 95% CIs. Adjusted models included participants’ sex, age, community type, education, occupation and marital status. Results Among 1825 participants, 358 (19.6%) had a recent migration history. Overall, migrants exhibited a significantly higher combined prevalence of curable STIs (gonorrhoea, chlamydia, high-titre syphilis (rapid plasma regain ≥1:8) and trichomoniasis) as compared with long-term residents (34.4% vs 24.2%; adjPRR=1.23; 95% CI 1.03 to 1.47). Significant differences in curable STI prevalence by migration status were concentrated among persons living with HIV (49.4% prevalence in migrants vs 32.6% in long-term residents; adjPRR=1.42; 95% CI 1.10 to 1.85) and among women (38.8% in migrants vs 27.8% in long-term residents; adjPRR=1.26; 95% CI 1.01 to 1.58). High-titre syphilis prevalence was especially elevated among male migrants (11.2% in migrants vs 4.9% in long-term residents; adjPRR=1.82; 95% CI 1.06 to 3.13). Conclusions The prevalence of non-HIV STIs is higher among migrants. Tailored outreach and service delivery approaches that address the needs of mobile populations are crucial for integrated HIV and STI epidemic control in Uganda to optimise resources and reduce transmission risks.

Objective Voluntary medical male circumcision (MC) is a critical tool in combination HIV prevention programmes in Africa. Self-reported MC (SrMC) status is used in HIV epidemiological surveys to assess MC coverage but is subject to response bias with limited validation. This study evaluated the utility of SrMC status as a marker of MC as well as self-reported genital lesions for genital ulcer disease (GUD) among Ugandan men. Methods Male participants aged 18–49 years in the cross-sectional Sexually Transmitted Infection Prevalence study, conducted between May and October 2019, responded to a questionnaire capturing SrMC status and current genital ulcer symptoms followed by clinical assessment to verify MC and presence of GUD. Sensitivity, specificity, positive predictive value, negative predictive value and corresponding CIs (95% CI) for SrMC status and GUD were estimated. Results There were 853 male participants, of whom 470 (55.1%) self-reported being circumcised and 23 (2.7%) self-reported GUD (SrGUD). MC was clinically confirmed in 50.2% (n=428) of participants with sensitivity of SrMC status at 99% (95% CI: 98% to 100%) and specificity 89% (95% CI: 86% to 92%). Specificity of SrMC was lowest among persons living with HIV and viremic (>1000 copies/mL) at 72% (95% CI: 46% to 90%). 18 participants had clinically confirmed GUD, but only 12 SrGUD symptoms, corresponding to a sensitivity and specificity of 67% (95% CI: 41% to 87%) and 99% (95% CI: 98% to 99%), respectively. Conclusions SrMC status is a robust proxy for clinically confirmed MC status and may reliably be used to assess MC coverage in this setting. Conversely, GUD symptoms were under-reported, which may impact effective syndromic management of sexually transmitted infections and warrants further examination.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15–24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15–24 years) from older men declined by about one-third, transmission to women (aged 25–34 years) from men that were 0–6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa.

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.

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years, but as new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance and longitudinal deep- sequence viral phylogenetics to assess how HIV incidence and the population groups driving transmission have evolved over a 15-year period from 2003 to 2018 in Uganda. HIV viral suppression increased more rapidly in women than men, resulting in 1.5-2 fold higher suppression rates in women with HIV by 2018 across age groups. Incidence declined more slowly in women than men, increasing pre-existing gender imbalance in HIV burden. Age-specific transmission flows shifted; the share of transmission to girls and women aged 15-24 years from older men declined by approximately one third, whereas the contribution of transmission to women aged 25-34 years from men aged 0-6 years older doubled from 2003 to 2018. We estimated closing the gender gap in viral sup- pression could have reduced HIV incidence in women by half in 2018 and ended gender disparities in incidence. This study suggests that male-targeted HIV pro- grams to increase HIV suppression are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa.