Background: There is limited information on factors that influence oral pre-exposure prophylaxis (PrEP) uptake and adherence among adolescent girls and young women (AGYW). We conducted a qualitative methods study to explore experiences, facilitators and barriers of PrEP uptake and adherence to PrEP among AGYW at risk of Human Immunodeficiency Virus (HIV) infection in Kampala, Uganda. Methods: This study was nested in a prospective cohort study that offered daily oral PrEP to AGYW. Between April 2019 and October 2020 we conducted in-depth interviews with 26 AGYW aged 14–24 years who had been offered or had been using PrEP for at least 6 months, including PrEP adherers (8), non-adherers (8) and those who had declined PrEP (10). After 12 months, follow-up interviews were conducted with 12 AGYW who had adhered to PrEP and those who had dropped it. Thematic analysis was conducted and data were further examined and categorized into the 5 constructs of the Socio-Ecological Model (SEM). Results: PrEP uptake and adherence were facilitated by factors including: perceptions that one’s own or partner’s sexual behaviour was high risk, a negative attitude towards condoms, social support and wanting to maintain a negative HIV status after receiving a negative HIV test result. Good adherence to PrEP was enabled by effective counselling, support tools such as alarms and phone reminders and incentives like free treatment for STIs and other illnesses during study visits. Barriers to uptake included: anxiety about the pill burden, perceptions of being too young for PrEP and fear of being labelled `prostitute’ or `HIV positive’. Poor adherence was attributed to doubt over the efficacy of PrEP as a result of beliefs that because HIV was incurable, no medicine could prevent it. Alcohol use, side effects experienced, and mobility all had a negative impact on adherence. The majority of PrEP users reported feeling safe as a result of using PrEP which had both good and negative implications on their sexual behaviour, specifically the number of sexual partners and condom use. Conclusion: Addressing community misconceptions to maximize uptake of PrEP among AGYW is important. Targeted education messages, and counselling to address misconceptions in ways that capture the attention of AGYW in communities are required.

Introduction: Oral pre‐exposure prophylaxis (PrEP) has been scaled up; however, data from real‐world settings are limited. We studied oral PrEP preference, uptake, adherence and continuation among adolescent girls and young women (AGYW) vulnerable to HIV in sub‐Saharan Africa.Methods: We conducted a prospective cohort study among 14‐ to 24‐year‐old AGYW without HIV who were followed for 12 months in Kampala, Uganda. Within at least 14 days of enrolment, they received two education sessions, including demonstrations on five biomedical interventions that are; available (oral PrEP), will be available soon (long‐acting injectable PrEP and anti‐retroviral vaginal ring) and in development (PrEP implant and HIV vaccine). Information included mode and frequency of delivery, potential side effects and method availability. Volunteers ranked interventions, 1 = most preferred to 5 = least preferred. Oral PrEP was “preferred” if ranked among the top two choices. All were offered oral PrEP, and determinants of uptake assessed using Poisson regression with robust error variance. Adherence was assessed using plasma tenofovir levels and self‐reports.Results: Between January and October 2019, 532 volunteers were screened; 285 enrolled of whom 265 received two education sessions. Mean age was 20 years (SD±2.2), 92.8% reported paid sex, 20.4% reported ≥10 sexual partners in the past 3 months, 38.5% used hormonal contraceptives, 26.9% had chlamydia, gonorrhoea and/or active syphilis. Of 265 volunteers, 47.6% preferred oral PrEP. Willingness to take PrEP was 90.2%; however, uptake was 30.6% (n = 81). Following enrolment, 51.9% started PrEP on day 14 (same day PrEP offered), 20.9% within 30 days and 27.2% after 30 days. PrEP uptake was associated with more sexual partners in the past 3 months: 2–9 partners (aRR = 2.36, 95% CI: 1.20–4.63) and ≥10 partners (aRR 4.70, 95% CI 2.41–9.17); oral PrEP preference (aRR 1.53, 95% CI 1.08–2.19) and being separated (aRR 1.55, 95% CI 1.04–2.33). Of 100 samples from 49 volunteers during follow up, 19 had quantifiable tenofovir levels (>10 μg/L) of which only three were protective (>40 μg/L).Conclusions: Half of AGYW preferred oral PrEP, uptake and adherence were low, uptake was associated with sexual behavioural risk and oral PrEP preference. Development of alternative biomedical products should be expedited to meet end‐user preferences and, community delivery promoted during restricted movement.

Across sub-Saharan Africa, key populations with elevated HIV-1 incidence and/or prevalence have been identified, but their contribution to disease spread remains unclear. We performed viral deep-sequence phylogenetic analyses to quantify transmission dynamics between the general population (GP), fisherfolk communities (FF), and women at high risk of infection and their clients (WHR) in central and southwestern Uganda. Between August 2014 and August 2017, 6185 HIV-1 positive individuals were enrolled in 3 GP and 10 FF communities, 3 WHR enrollment sites. A total of 2531 antiretroviral therapy (ART) naïve participants with plasma viral load >1000 copies/mL were deep-sequenced. One hundred and twenty-three transmission networks were reconstructed, including 105 phylogenetically highly supported source–recipient pairs. Only one pair involved a WHR and male participant, suggesting that improved population sampling is needed to assess empirically the role of WHR to the transmission dynamics. More transmissions were observed from the GP communities to FF communities than vice versa, with an estimated flow ratio of 1.56 (95% CrI 0.68–3.72), indicating that fishing communities on Lake Victoria are not a net source of transmission flow to neighboring communities further inland. Men contributed disproportionally to HIV-1 transmission flow regardless of age, suggesting that prevention efforts need to better aid men to engage with and stay in care.

Background: Although cervical cancer is preventable, most women in sub-Saharan Africa (SSA) do not receive routine screening and few treatment options exist. Female Sex Workers (FSWs) are among the Ugandan female population at highest risk of acquiring sexually transmitted infections (STIs) including HIV and human papilloma viruses (HPV), the cause of cervical cancer. We report one-year experiences of visual inspection with acetic acid (VIA) positivity among FSWs in the early detection of pre-cancerous and cancerous cervical lesions in Kampala, Uganda. Methods: Between June 2014 and July 2015, we enrolled FSWs into a cross-sectional study at a research clinic. The women were screened using the VIA method (application of 3–5 % acetic acid to the cervix). All VIA positive women were referred to a tertiary hospital for colposcopy, biopsy, and immediate treatment (if indicated) at the same visit according to national guidelines. Data on socio-demographic, sexual behaviour, sexual reproductive health and clinical characteristics were collected. We used logistic regression to identify factors associated with VIA positivity. Results: Of 842 women assessed for eligibility, 719 (85 %) of median age 30 (IQR 26, 35) were screened, and 40 (6 %) women were VIA positive. Of the 24 histology specimens analysed, 6 showed inflammation, only 1 showed cervical intraepithelial neoplasia (CIN) 1, 13 women showed CIN2/3, while 4 women already had invasive cervical cancer. The overall prevalence of HIV was 43 %, of whom only 35 % were receiving ART. In the age-adjusted analysis, VIA positivity was more likely among women who reported having > 100 life-time partners (aOR = 3.34, 95 %CI: 1.38–8.12), and HIV positive women (aOR = 4.55; 95 %CI: 2.12–9.84). Conclusions: We found a relatively low proportion of VIA positivity in this population. The experience from our program implies that the VIA results are poorly reproducible even among a category of trained professional health workers. VIA positivity was more likely among women with a high number of sexual partners and HIV infection. Interventions for improving cervical cancer screening should be recommended as part of HIV care for FSWs to reduce the disease burden in this population.

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vaccines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vaccination serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4⁺ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abrogated vaccine responses in communities with endemic infections.

Alcohol-related harms may be increased among adolescent girls and young women (AGYW) involved in sex work, yet data on alcohol misuse among AGYW in sub-Saharan Africa are still scarce. We conducted a cross-sectional study among 15–24-year-old AGYW from January 2013 to December 2018 in Kampala, Uganda and used the Alcohol Use Disorder Identification Test (AUDIT) to study alcohol use patterns and dependence symptoms (dependence score ≥4). Of 1440 participants (median age 21 years), 83.1% had less than secondary education, 79.8% reported ≥10 paying sexual partners in the past month, 46.0% had ever experienced intimate partner violence (IPV), and 20.6% were living with HIV. Overall, 59.9% scored ≥8 and 29.4% scored ≥16 on the AUDIT. Of 277 (15.8%) with dependence symptoms, 69.1% were screened alcohol dependent. An AUDIT score ≥8 was associated with older age, illicit drug use, experiencing IPV, inconsistent condom use with paying partners, and HIV sero-negativity. All factors remained associated with a higher score ≥16 except HIV status. Similarly, illicit drug use, experiencing IPV and inconsistent condom use were associated with dependence symptoms and, in addition, a higher number of paying sexual partners. Alcohol misuse is high in this population, they urgently need harmful substance use reduction interventions.