Preference for novel biomedical HIV pre-exposure prophylaxis methods among adolescent girls and young women in Kampala, Uganda: a mixed methods study.

Background: Novel HIV pre-exposure prophylaxis (PrEP) methods including a potential future HIV vaccine, will increase prevention options for adolescent girls and young women (AGYW) at high risk of HIV infection in Eastern and Southern Africa, yet data on AGYW's preferences for various PrEP methods is limited. We investigated preferences for five biomedical PrEP methods (oral, injectable, vaginal ring, implant, HIV vaccine) among 14-24-years-old AGYW in Kampala, Uganda. Methods: From January to December 2019, we conducted a mixed methods study including 265 high-risk AGYW. After receiving two education sessions on the five PrEP methods, participants were asked about their "most preferred PrEP method." Multinomial logistic regression (oral PrEP as reference category) was used to determine participant characteristics associated with method preference. Results are presented as adjusted relative risk ratios (aRRR) with 95% confidence intervals (CI). In-depth interviews were conducted with 20 selected participants to examine reasons influencing PrEP preferences and suggestions for method improvements. Transcripts were analyzed thematically. Results: Participants preferred methods were: HIV vaccine (34.7%), oral PrEP (25.7%), injectable PrEP (24.9%), PrEP implant (13.6%), and vaginal ring (1.1%). Preference for injectable PrEP increased with every year of age (aRRR 1.22; 95% CI 1.04-1.44) and among participants with chlamydia or gonorrhoea (aRRR 2.53; 95% CI 1.08-5.90), while it was lower among participants having sexual partner(s) living with HIV or of unknown HIV status (aRRR 0.30; 95% CI 0.10-0.91). Preference for PrEP implants also increased with age (aRRR 1.42; 95% CI 1.14-1.77) and was strong among participants having ≥10 sexual partners in the past 3 months (aRRR 3.14; 95% CI 1.16-8.55), while it was lower among those with sexual partner(s) living with HIV or of unknown HIV status (aRRR 0.25; 95% CI 0.07-0.92). PrEP method preference was influenced by product attributes and prior experiences with similar product forms commonly used in health care. Conclusion: AGYW have varied preferences for biomedical PrEP method and those with higher sexual behavioral risk prefer long-acting methods. As we anticipate more available PrEP options, oral PrEP use should be supported among AGYW, especially for those with sexual partners living with HIV or of unknown HIV status.

Prevalence and Factors Associated with Illicit Drug and High-Risk Alcohol Use among Adolescents Living in Urban Slums of Kampala, Uganda.

Background; Illicit drug and high risk alcohol use among adolescents leads to poor health outcomes. We enrolled adolescents from urban slums in Kampala, Uganda, to assess baseline prevalence, and factors associated with illicit drug and high-risk alcohol consumption. Methods; We conducted a cross-sectional study using data collected in a cohort that enrolled 14-19-year-old male and female participants from 25-March-2019 to 30-March 2020. Data was collected on social-demographics, sexual behavior and reproductive health using interviewer administered questionnaires. The main outcomes were illicit drug use and high-risk alcohol use. Data on alcohol use was collected using the Alcohol Use Disorder Identification Test (AUDIT); results were dichotomized. Factors associated with each outcome were analyzed using multivariable logistic regression. Results; We enrolled 490 participants (60.6% female) with median age 18 (IQR 17-18) years, 91.0% had less than secondary education, 48.4% had their sexual debut before 15years, 47.1% reported paid sex in the past 3 months and 24.7% had a sexually transmitted infection (chlamydia, gonorrhea and/ or active syphilis) at enrolment. The prevalence of illicit drug use was 34.9% while 16.1% were screened as high-risk alcohol users. Illicit drug use was associated with being male (aOR 9.62; 95% CI 5.74-16.11), being married (aOR 2.24; 95%CI 1.07-4.68) and having ≥10 paying sexual partners in the past 3 months (aOR 3.13; 95%CI 1.40-6.98). High risk alcohol use was associated with reporting sex work as the main job (aOR 3.19; 95%CI 1.02-9.94) and having experienced physical (aOR 1.96 95%CI 1.01-3.81) or emotional violence (aOR 2.08; 95%CI 1.14-3.82) from sexual partners. Conclusion: Illicit drug and high-risk alcohol use are prevalent among adolescents involved in high risk sexual behavior and living in urban slums of Kampala. Comprehensive interventions that target substance use among this group of young people are needed and should include measures against intimate partner violence.

"I fear those things": non-uptake of contraceptives, and barriers to use among adolescent girls and young women at high risk of HIV infection in Kampala, Uganda.

Background: Adolescent girls and young women involved in risky behaviors are vulnerable to multiple health problems, yet sexual and reproductive health services remain underutilized. We evaluated factors associated with non-uptake of contraceptives and barriers to use among adolescent girls and young women (14-24 years old) at high risk of HIV infection in an environment where contraceptives were provided at no cost. Methods: We conducted a mixed methods study, utilizing data from a baseline cross sectional survey and qualitative in-depth interviews. Survey participants tested negative for pregnancy and reported willingness to use contraception. Non-uptake of contraceptives was defined as not taking contraception at any study visit (baseline and throughout the study). Logistic regression model was used to assess factors associated with non-uptake of contraceptives. We purposively selected participants for interviews to discuss their knowledge and experiences with contraceptives and make suggestions to improve uptake. Qualitative data were analyzed thematically. Results: All 285 participants were included in the analysis. Out of the 285 participants 127 were not using contraceptives and of the 127, 44 (34.6%) did not take up any method throughout the study while 43 of the 83 remaining participants (who took up a method) chose male condoms only. Non-uptake of contraceptives was less likely among older women (20-24 years) (aOR = 0.32, 95% CI 0.16-0.89) compared to younger women (less than 20 years). Qualitative data showed that concerns about future fertility, fear of associated side effects and influence from close relations contributed to non-uptake of contraception. Conclusion: Non-uptake of contraceptives was common despite the promotion and provision of contraceptives in the context of a research study mainly because adolescents lack autonomy while making contraceptive decisions. Identifying and addressing their concerns and continued counselling on contraceptive use alongside condom promotion may improve uptake and utilization of contraceptives.

The bacterial profile and antibiotic susceptibility pattern in respiratory tract samples from art-experienced HIV-positive adults in Uganda.

INTRODUCTION: Microbial infections are a major cause of morbidity and mortality among people living with HIV (PLWH). Respiratory tract infections (RTIs) are responsible for approximately 70% of illnesses among PLWH. Drug resistant bacteria are highly prevalent among PLWH and this is a public health concern. METHODS: This is a retrospective analysis of data collected during the COSTOP trial between 2011 and 2013. Sputum collected on spot from participants presenting with a productive cough was examined using Gram, Ziehl-Neelsen stains and cultured on suitable bacteriological media. Antimicrobial sensitivity testing was done on isolated pathogens, by disc diffusion technique. RESULTS: We included 687 participants with mean age 41.3 (SD 8.2) years of whom 76.4% were female. Two hundred one sputum samples grew bacteria; Moraxella species (27.4%), Streptococcus pneumoniae(25.4%), Haemophilus influenza(22.4%), Mycobacterium species(4.5%), Pseudomonas species(4.0%), Staphylococcus aureus(4.0%), Escherichia coli (1.0%), Klebsiella species (1.0%), other bacteria (10.4%). A higher monthly income greater than or equal to 30$ (aOR = 0.63, 95%CI: 0.40-0.99) and longer duration since HIV diagnosis (aOR = 1.06, 95%CI: 1.0-1.11) were found to be independently associated with a positive bacterial culture. Moraxella sp, H. influenza and Pseudomonas had zero sensitivity towards cotrimoxazole. Sensitivity to erythromycin was low among Moraxella sp (28.6%), H. influenza (31.6%) and S. aureus(42.9%) and other bacteria (42.9%). Most isolates were sensitive to Amoxicillin + Clavulanic acid and ceftriaxone. CONCLUSION: There is a very low sensitivity of isolated bacteria to commonly prescribed antibiotics that are more available through the national supply chain, which is of public health concern. Urgent steps to tackle the high antimicrobial resistance among PLWH is required.

Prevalence and Factors Associated with Illicit Drug and High-Risk Alcohol Use among Adolescents Living in Urban Slums of Kampala, Uganda.

Background: Illicit drug and high risk alcohol use among adolescents leads to poor health outcomes. We enrolled adolescents from urban slums in Kampala, Uganda, to assess baseline prevalence, and factors associated with illicit drug and high-risk alcohol consumption. Methods: We conducted a cross-sectional study using data collected in a cohort that enrolled 14-19-year-old male and female participants from 25-March-2019 to 30-March 2020. Data was collected on social-demographics, sexual behavior and reproductive health using interviewer administered questionnaires. The main outcomes were illicit drug use and high-risk alcohol use. Data on alcohol use was collected using the Alcohol Use Disorder Identification Test (AUDIT); results were dichotomized. Factors associated with each outcome were analyzed using multivariable logistic regression. Results: We enrolled 490 participants (60.6% female) with median age 18 (IQR 17-18) years, 91.0% had less than secondary education, 48.4% had their sexual debut before 15years, 47.1% reported paid sex in the past 3 months and 24.7% had a sexually transmitted infection (chlamydia, gonorrhea and/ or active syphilis) at enrolment. The prevalence of illicit drug use was 34.9% while 16.1% were screened as high-risk alcohol users. Illicit drug use was associated with being male (aOR 9.62; 95% CI 5.74-16.11), being married (aOR 2.24; 95%CI 1.07-4.68) and having ≥10 paying sexual partners in the past 3 months (aOR 3.13; 95%CI 1.40-6.98). High risk alcohol use was associated with reporting sex work as the main job (aOR 3.19; 95%CI 1.02-9.94) and having experienced physical (aOR 1.96 95%CI 1.01-3.81) or emotional violence (aOR 2.08; 95%CI 1.14-3.82) from sexual partners. Conclusion: Illicit drug and high-risk alcohol use are prevalent among adolescents involved in high risk sexual behavior and living in urban slums of Kampala. Comprehensive interventions that target substance use among this group of young people are needed and should include measures against intimate partner violence.

Hepatitis B status and associated factors among participants screened for simulated HIV vaccine efficacy trials in Kenya and Uganda.

INTRODUCTION: Hepatitis B (HBV) prevalence remains high in Sub Saharan Africa and among some key populations such as those with continued exposure through sexual contact. We assessed the HBV status among potential participants who were screened for simulated HIV vaccine efficacy trials in Kenya and Uganda. METHODS: We conducted a cross sectional analysis of data collected from individuals who were screened in Kenya (Nairobi) and Uganda (Entebbe and Kampala). The studies followed hypothetical procedures of an HIV vaccine efficacy trial and aimed to enroll HIV negative key and vulnerable populations at elevated risk of HIV acquisition. HBV status was the main outcome categorized using Hepatitis B surface antigen (HBsAg) and total Hepatitis B core antibody (HBcAb). Baseline characteristics potentially associated with never being infected were analyzed using logistic regression. RESULTS: We screened 1,366 participants with mean age (SD) 28.7 (7.3) years. Overall, 46.6% were from Entebbe, 50.7% had secondary or higher level of education, 76.4% had informal high-risk jobs and 56.3% were male. Kampala had only female participants contributing 60.6% of females screened. Of the screened participants, 94.7% and 3.4% were negative and positive for HBsAg respectively. The prevalence on HBV infection was 3.9% among males and 2.8% among females while prevalence by site was: Entebbe (4.9%); Kampala (4.1%) and Nairobi (0.3%). The highest HBV prevalence was found among participants aged 25-29-years (5.2%), those with primary level education (4.5%), and those in informal low risk jobs (6.5%). Considering 1265 participants with complete data on HBsAg and HBcAb-Total, HBV status was never infected (67.9%), past infection (28.5%), chronic infection (3.2%) and acute infection (0.5%). Of 859 who were never infected, 685 (79.7%) were tested for anti-HBs titers of whom 60 (8.8%) had titers >10IU/L (immune due to vaccination). The odds of never being HBV infected were lower among older individuals 25-29 years (AOR 0.51; 95%CI 0.36-0.71) and ≥30 years (AOR 0.35; 95% CI 0.25-0.49). The odds were higher among participants with informal high-risk jobs from Kampala (AOR 2.21; 95% CI 1.41-3.47) and Nairobi (AOR 2.61; 95% CI 1.72-4.00) compared to those from Entebbe. CONCLUSION: HBV prevalence and immunity due to vaccination were low among HIV negative individuals who are eligible for HIV vaccine trials and prevalence varies by age, education level and main occupation. Younger individuals and those recruited from existing cohorts/ clinics have a higher likelihood of having no prior HBV infection. HIV prevention intervention trials are a platform to identify individuals that need HBV vaccination.

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.

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-1ß, 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.

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.

The impact of endemic infections on protective immunity is critical to inform vaccination strategies. In this study, we assessed the influence of Schistosoma mansoni infection on host responses in a Ugandan fishing cohort given a Hepatitis B (HepB) vaccine. Concentrations of schistosome-specific circulating anodic antigen (CAA) pre-vaccination showed a significant bimodal distribution associated with HepB titers, which were lower in individuals with high CAA. We established that participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination and higher regulatory T cells (Tregs) post-vaccination. Polarization towards higher frequencies of Tregs: cTfh cells can be mediated by changes in the cytokine environment favoring Treg differentiation. In fact, we observed higher levels of CCL17 and soluble IL-2R pre-vaccination (important for Treg recruitment and development), in individuals with high CAA that negatively associated with HepB titers. Additionally, alterations in pre-vaccination monocyte function correlated with HepB titers, and changes in innate-related cytokines/chemokine production were associated with increasing CAA concentration. We report, that by influencing the immune landscape, schistosomiasis has the potential to modulate immune responses to HepB vaccination. These findings highlight multiple Schistosoma -related immune associations that could explain abrogated vaccine responses in communities with endemic infections. Author Summary: Schistosomiasis drives host immune responses for optimal pathogen survival, potentially altering host responses to vaccine-related antigen. Chronic schistosomiasis and co-infection with hepatotropic viruses are common in countries where schistosomiasis is endemic. We explored the impact of Schistosoma mansoni ( S. mansoni ) infection on Hepatitis B (HepB) vaccination of individuals from a fishing community in Uganda. We demonstrate that high schistosome-specific antigen (circulating anodic antigen, CAA) concentration pre-vaccination, is associated with lower HepB antibody titers post-vaccination. We show higher pre-vaccination levels of cellular and soluble factors in instances of high CAA that are negatively associated with HepB antibody titers post-vaccination, which coincided with lower frequencies of circulating T follicular helper cell populations (cTfh), proliferating antibody secreting cells (ASCs), and higher frequencies of regulatory T cells (Tregs). We also show that monocyte function is important in HepB vaccine responses, and that high CAA is associated with alterations in the early innate cytokine/chemokine microenvironment. Our findings suggest that in individuals with high CAA and likely high worm burden, schistosomiasis creates and sustains an environment that is polarized against optimal host immune responses to the vaccine, which puts many endemic communities at risk for infection against HepB and other diseases that are preventable by vaccines.

Incidence of unintended pregnancy and associated factors among adolescent girls and young women at risk of HIV infection in Kampala, Uganda.

Background: In sub-Saharan Africa, one in every five young women becomes pregnant, and 50% of these are unintended. Pregnancies in adolescent girls and young women (AGYW) are associated with poorer maternal and neonatal outcomes and a high abortion rate, yet data are still limited on incident pregnancies among AGYW in vulnerable situations. We studied the incidence and factors associated with unintended pregnancy among AGYW who were frequently engaged in transactional sex in Kampala, Uganda. Methods: We analyzed data from a study that investigated the uptake of oral pre-exposure prophylaxis among AGYW from January 2019 to December 2020. Volunteers attended 3-monthly study visits for 12 months each. Contraceptive services were provided to interested volunteers free of charge. Interviewers collected data on sociodemographics, sexual behavior, reproductive health outcomes, and substance use. Pregnancy was determined by testing for beta-human chorionic gonadotropin hormone in urine. The pregnancy incidence rate was estimated using the Kaplan-Meier technique, and logistic regression was used to determine the correlates of pregnancy. Results: We included 285 volunteers with a mean age of 19.9 [standard deviation (SD), ± 2.24] years; 54.7% had attained secondary school education or higher, 57.2% were single (never married), 92.6% reported engaging in transactional sex, 21.0% reported sex work as their main job, 51.9% consumed alcohol in the month prior to the interview, of whom 12.8% consumed alcohol daily, and 25.3% had Chlamydia trachomatis/Neisseria gonorrhoeae. The mean age at first sexual intercourse was 15.7 (SD, ±2.1) years. We recorded 44 pregnancies over 187.2 person-years of follow-up, an incidence of 23.5 per 100 person-years [95% confidence interval (CI), 17.5-31.6]. Incident pregnancies were more likely among volunteers who had ≥10 sexual partners in the past 3 months [adjusted risk ratio (aRR) 1.97; 95% CI, 1.05-3.70] and those who reported not using contraception (aRR 5.89; 95% CI, 2.74-12.66). Incident pregnancies were less likely among those who reported alcohol consumption in the past month (aRR 0.52; 95% CI, 0.30-0.90). Conclusion: The incidence of unintended pregnancy was high despite the availability of free contraceptive services. We recommend sociobehavioral studies to explore this further. Sexual and reproductive health campaigns should strengthen demand creation and motivation to use contraception among young women with multiple sexual partners.

Prevalence, Perpetrators, and Factors Associated With Intimate Partner Violence Among Adolescents Living in Urban Slums of Kampala, Uganda.

Intimate partner violence (IPV) poses a public health burden, yet few studies have assessed co-existence of physical, emotional, and sexual IPV among adolescents. We assessed recent IPV victimization and associated factors and described IPV patterns and perpetrators among young people from urban slums in Kampala, Uganda. We conducted a prospective cohort study among 14 to 19-year-old individuals enrolled from March 2019 to March 2020 and followed quarterly for 12 months. We collected data on socio-demographics, sexual behavior, and substance use through interviews. Recent IPV victimization was documented at all visits if a participant reported experiencing physical, emotional, and/or sexual IPV in the past 3 months. Baseline factors associated with recent IPV victimization were determined using multivariable logistic regression. We enrolled 490 adolescents (60.6% female) with median age 18 years (Interquartile range (IQR) 17-18 years), 91.0% had less than secondary level education. Females mainly engaged in sex work (17.5%) and selling fruits/snacks (9.1%) while males commonly earned from sale of metal scrap or plastic waste (28.5%), 41% reported ≥10 life-time sexual partners, 16.1% were high-risk alcohol drinkers and 34.9% used illicit drugs in the past 3 months. Overall, 27.8% reported recent IPV victimization (20.0% females) with emotional IPV being common (17.8%). At baseline, recent IPV victimization was associated with high-risk alcohol consumption (adjusted odds ratio [aOR] 2.57; 95% confidence interval [CI] [1.44, 4.58]), reported paid sex in the past 3 months (aOR 1.82; [1.02, 3.22]) and being separated (aOR 2.47; [1.29, 4.73]). Recent IPV victimization declined from baseline to month 9 and increased at month 12 visits which coincided with the COVID-19 pandemic. IPV victimization is high among young people living in urban slums with emotional IPV being prevalent. IPV interventions are needed and should also address excessive alcohol consumption.

Uptake of and adherence to oral pre-exposure prophylaxis among adolescent girls and young women at high risk of HIV-infection in Kampala, Uganda: A qualitative study of experiences, facilitators and barriers.

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.

Use of Services among Female Sex Workers Receiving a Comprehensive HIV Enhanced Prevention Intervention in Kampala, Uganda: A Cross-sectional Study.

We estimated the prevalence and factors associated with the use of a dedicated HIV prevention, care, and treatment service for female sex workers (FSWs) in Kampala, Uganda. Between October 2017 to January 2018, we conducted a cross-sectional study among FSWs at a dedicated clinic. We defined use as the use of the HIV prevention, care, and treatment services by FSWs at least once within the past six months. We used the log-binomial model to determine the factors associated with use of clinic services. Eight hundred and seventy-four women were included in the analysis. The overall prevalence of use of clinic services was 81%. At adjusted analysis, use of clinic services was independently associated with being HIV positive and being treated for STIs in the past three months. The prevalence of use of clinic services was high. Dedicated services for FSWs are required to support their use of HIV and STI care.

Low awareness of oral and injectable PrEP among high-risk adolescent girls and young women in Kampala, Uganda.

BACKGROUND: Adolescent girls and young women (AGYW) account for a disproportionate number of new HIV infections worldwide. HIV prevalence among young sex workers in Uganda is 22.5%. Although pre-exposure prophylaxis (PrEP) is a highly effective biomedical HIV prevention method, awareness of PrEP among AGYW in Uganda has not been studied systematically. We aimed to assess awareness of PrEP and factors associated with awareness of PrEP among AGYW who frequently reported paid sex. METHODS: We conducted a cross-sectional study among 14-24-year old AGYW at high risk of HIV infection in Kampala, Uganda from January to October 2019. Participants were screened for PrEP eligibility using a national screening tool of whom 82.3% were eligible. Data on socio-demographics, behavioral and sexual risks were collected by interview. Awareness of oral or injectable PrEP, the latter of which is currently in late-stage trials, was defined as whether an individual had heard about PrEP as an HIV prevention method. Multivariable robust poisson regression model was used to assess factors associated with oral PrEP awareness. RESULTS: We enrolled 285 participants of whom 39.3% were under 20 years old, 54.7% had completed secondary education, 68.8% had multiple sex partners in the past 3 months, 8.8% were screened as high risk drinkers'/ alcohol dependent (AUDIT tool) and 21.0% reported sex work as main occupation. Only 23.2% were aware of oral PrEP and 3.9% had heard about injectable PrEP. The prevalence of oral PrEP awareness was significantly higher among volunteers screened as alcohol dependents (aPR 1.89, 95% CI 1.08-3.29) and those with multiple sexual partners (aPR 1.84, 95% CI 1.01-3.35), but was lower among those who reported consistent condom use with recent sexual partners (aPR 0.58, 95% CI 0.37-0.91). CONCLUSIONS: Majority of AGYW were not aware of any kind of PrEP. Those with higher risk behavior, i.e. alcohol dependents or multiple sexual partners, were more aware of oral PrEP. Interventions to increase awareness among female youth are needed. Improving PrEP awareness is critical to increasing PrEP uptake among high-risk AGYW in Uganda.

Oral pre-exposure prophylaxis preference, uptake, adherence and continuation among adolescent girls and young women in Kampala, Uganda: a prospective cohort study.

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.

"I prefer to take pills when I plan to have sex": Perceptions of on-demand versus daily oral pre-exposure prophylaxis among adolescents in Kampala, Uganda.

There is limited information about the use of on-demand and daily pre-exposure prophylaxis (PrEP) among adolescents and young people (AYP) in sub-Saharan Africa. We explored perceptions of both regimens among 14- to 19-year-olds perceived to be at high risk of HIV infection in Kampala, Uganda, using qualitative data collection methods. Data were analysed by theme and interpreted based on constructs from the framework of acceptability. Although there were no noticeable gender differences in preferences for a particular regimen, acceptability of PrEP depended on individual AYP sexual behaviour at the time of the study. Those who perceived themselves to be at increased risk of acquiring HIV preferred using daily PrEP, citing the consistency that comes from taking a pill daily and which they considered to be efficacious and safe. AYP who had less frequent sex preferred on-demand PrEP because it would enable them to "plan for sex". However, both groups perceived taking daily PrEP to be a burden, which was an impediment to acceptance of this form of PrEP. AYP anticipated that daily pill taking would be very stressful, requiring a lot of effort and would interrupt their daily routine. Therefore, while both on-demand and daily PrEP were acceptable and beneficial to these AYP, preferences for either regimen depended on self-perceived risk. Thus, oral PrEP use should be tailored to end-user preferences and risk profiles.

Visual inspection with acetic acid (VIA) positivity among female sex workers: a cross-sectional study highlighting one-year experiences in early detection of pre-cancerous and cancerous cervical lesions in Kampala, Uganda.

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.

Use of propensity score matching to create counterfactual group to assess potential HIV prevention interventions.

The design of HIV prevention trials in the context of effective HIV preventive methods is a challenge. Alternate designs, including using non-randomised 'observational control arms' have been proposed. We used HIV simulated vaccine efficacy trials (SiVETs) to show pitfalls that may arise from using such observational controls and suggest how to conduct the analysis in the face of the pitfalls. Two SiVETs were nested within previously established observational cohorts of fisherfolk (FF) and female sex workers (FSW) in Uganda. SiVET participants received a licensed Hepatitis B vaccine in a schedule (0, 1 and 6 months) similar to that for a possible HIV vaccine efficacy trial. All participants received HIV counselling and testing every quarter for one year to assess HIV incidence rate ratio (IRR) between SiVET and non-SiVET (observational data). Propensity scores, conditional on baseline characteristics were calculated for SiVET participation and matched between SiVET and non-SiVET in the period before and during the SiVET study. We compared IRR before and after propensity score matching (PSM). In total, 3989 participants were enrolled into observational cohorts prior to SiVET, (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). SiVET enrolled 572 participants (Jul 2012 to Apr 2014 in FF and Aug 2014 to Apr 2017 in FSW), with 953 non-SiVET participants observed in the SiVET concurrent period and 2928 from the pre-SiVET period (before Jul 2012 in FF or before Apr 2014 in FSW). Imbalances in baseline characteristics were observed between SiVET and non-SiVET participants in both periods before PSM. Similarly, HIV incidence was lower in SiVET than non-SiVET; SiVET-concurrent period, IRR = 0.59, 95% CI 0.31-0.68, p = 0.033 and pre-SiVET period, IRR = 0.77, 95% CI 0.43-1.29, p = 0.161. After PSM, participants baseline characteristics were comparable and there were minimal differences in HIV incidence between SiVET and non-SiVET participants. The process of screening for eligibility for efficacy trial selects participants with baseline characteristics different from the source population, confounding any observed differences in HIV incidence. Propensity score matching can be a useful tool to adjust the imbalance in the measured participants' baseline characteristics creating a counterfactual group to estimate the effect of interventions on HIV incidence.

Abortion and its correlates among female fisherfolk along Lake Victoria in Uganda.

INTRODUCTION: In Uganda, people living in fishing communities tend to engage in high-risk sexual activity which leads to unintended pregnancies that may end in abortions. Abortion has negative social, psychological, and medical impacts. We determined the frequency of abortion and its correlates among female fisher-folk along Lake Victoria in Uganda. METHODS: A cross-sectional survey was conducted among women aged 15- 49 years from Kigungu and Nsazi fishing communities. Data were collected on socio-demographic characteristics, abortion, and family planning use. Associations between abortion and participant characteristics were assessed using logistic regression models. RESULTS: Of the 713 women interviewed, 36, 5% were pregnant and 247, 34.6 % were using contraception. Majority (600, 84.2%) of those interviewed reported ever being pregnant. Approximately 45% of the pregnancies were un-intended while a third of those who had ever been pregnant (195, 32.5%) reported having aborted before. Slightly over a third (247, 34.6%) reported currently using or ever using family planning. Women aged 30+ years were more likely to abort compared to those aged 15-29 years (aOR: 2.7; 95% CI: 1.23-5.91). Women who had living children were less likely to abort compared to those who didn't have any living child (aOR: 0.06; 95% CI: 0.01 - 0.17). CONCLUSION: The rate of abortion among female fisher-folk in Uganda is substantial. Family planning use is still low and unintended pregnancies are common. Abortion risk increased with the age of the mother. Continuous behavioral change communication and optimization of family planning use are recommended to reduce abortions.

Willingness of female sex workers in Kampala, Uganda to participate in future HIV vaccine trials: a case control study.

BACKGROUND: We anticipate large efficacy trials of novel HIV vaccines that have shown acceptable safety profiles. We determined willingness to participate (WTP) in future HIV vaccine efficacy trials among HIV negative female sex workers (FSWs) in Kampala Uganda. METHODS: We conducted a case control study in the Good Health for Women Project cohort. Cases received HIV prevention services and, enrolled in a 12-month simulated vaccine efficacy trial (SiVET) that used Hepatitis B vaccine; they underwent vaccine trial procedures as would be in an actual trial. Controls received similar health services but did not enroll in SiVET. We matched cases and controls (ratio 2:1) for age and duration in the cohort. We described a hypothetical HIV vaccine trial to cases (after 9 months in SiVET) and controls including trial attributes: randomization, delaying pregnancy, frequent blood draws (80-100mls) and study visits for 3 years. We compared WTP and willingness for vaccine trial attributes by case/control using chi-squared or Fisher's exact tests and fitted conditional logistic regression models to determine independent predictors of WTP. RESULTS: We analyzed data for 311 volunteers (219 cases, 92 controls); median age 27 years (IQR: 23-32), 39.9% had ≥secondary education, 57.9% had sex work as their main job and 81.9% used illicit drugs. Compared to controls, more cases had lived in the community for > 1 year, (85.4% vs 64.1%; p < 0.001) and fewer cases reported illicit drug use in the past 3 months, (79.0% vs 89.1%; p = 0.03). Overall, 278 (89.4%) volunteers expressed WTP in an HIV vaccine trial, the most common reason being hope of protection against HIV. More cases than controls (58.2% vs 44.7%) did not need to consult anyone before trial participation (p = 0.03); cases were more willing to delay pregnancy (99.0% vs 94.0%; p = 0.03). Combining vaccine trial attributes, 249 (89.6%) of the 278 accepted all attributes. After controlling for case/ control status women with secondary education or higher expressed less WTP (aOR 0.17; 95% CI 0.04-0.80). CONCLUSION: FSWs in Kampala demonstrated high WTP. Prior experience with trial requirements like contraception may improve their uptake during actual trials. Family involvement is important for those without prior trial experience.

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02-2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94-0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32-4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.