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.

Predicting stress in first-year college students using sleep data from wearable devices.

Consumer wearables have been successful at measuring sleep and may be useful in predicting changes in mental health measures such as stress. A key challenge remains in quantifying the relationship between sleep measures associated with physiologic stress and a user's experience of stress. Students from a public university enrolled in the Lived Experiences Measured Using Rings Study (LEMURS) provided continuous biometric data and answered weekly surveys during their first semester of college between October-December 2022. We analyzed weekly associations between estimated sleep measures and perceived stress for participants (N = 525). Through mixed-effects regression models, we identified consistent associations between perceived stress scores and average nightly total sleep time (TST), resting heart rate (RHR), heart rate variability (HRV), and respiratory rate (ARR). These effects persisted after controlling for gender and week of the semester. Specifically, for every additional hour of TST, the odds of experiencing moderate-to-high stress decreased by 0.617 or by 38.3% (p<0.01). For each 1 beat per minute increase in RHR, the odds of experiencing moderate-to-high stress increased by 1.036 or by 3.6% (p<0.01). For each 1 millisecond increase in HRV, the odds of experiencing moderate-to-high stress decreased by 0.988 or by 1.2% (p<0.05). For each additional breath per minute increase in ARR, the odds of experiencing moderate-to-high stress increased by 1.230 or by 23.0% (p<0.01). Consistent with previous research, participants who did not identify as male (i.e., female, nonbinary, and transgender participants) had significantly higher self-reported stress throughout the study. The week of the semester was also a significant predictor of stress. Sleep data from wearable devices may help us understand and to better predict stress, a strong signal of the ongoing mental health epidemic among college students.

HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .01-.48]; P = .009), which warrants further studies to explore its role on HIV-1-specific immunopathogenesis.

Finding women in fishing communities around Lake Victoria: "Feasibility and acceptability of using phones and tracking devices".

INTRODUCTION: Women in fishing communities have both high HIV prevalence and incidence, hence they are a priority population for HIV prevention and treatment interventions. However, their mobility is likely to compromise the effectiveness of interventions. We assessed the acceptability, feasibility and of using phones and global positioning system (GPS) devices for tracking mobility, to inform future health research innovations. METHODS: A mult-site formative qualitative study was conducted in six purposively selected Fishing Communities on the shores of Lake Victoria in Kenya, Tanzania, and Uganda. Participants were selected based on duration of stay in the community and frequency of movement. Sixty-four (64) women participated in the study (16 per fishing community). Twenty-four (24) participants were given a study phone; 24 were asked to use their own phones and 16 were provided with a portable GPS device to understand what is most preferred. Women were interviewed about their experiences and recommendations on carrying GPS devices or phones. Twenty four (24) Focus Group Discussions with 8-12 participants were conducted with community members to generate data on community perceptions regarding GPS devices and phones acceptability among women. Data were analyzed thematically and compared across sites/countries. RESULTS: Women reported being willing to use tracking devices (both phones and GPS) because they are easy to carry. Their own phone was preferred compared to a study phone and GPS device because they were not required to carry an additional device, worry about losing it or be questioned about the extra device by their sexual partner. Women who carried GPS devices suggested more sensitization in communities to avoid domestic conflicts and public concern. Women suggested changing the GPS colour from white to a darker colour and, design to look like a commonly used object such as a telephone Subscriber Identity Module (SIM) card, a rosary/necklace or a ring for easy and safe storage. CONCLUSION: Women in the study communities were willing to have their movements tracked, embraced the use of phones and GPS devices for mobility tracking. Devices need to be redesigned to be more discrete, but they could be valuable tools to understanding movement patterns and inform design of interventions for these mobile populations.

Are we practicing what we preach? Family partnership in therapeutic residential care for children and youth.

This study presents a tiered conceptualization of family partnership developed by the Family-Run Executive Director Leadership Association (FREDLA) with examples of strategies from the literature. This sub-study was part of an overarching systematic review project that aimed to review the literature on family partnership in relation to youth outcomes. The tiers of family partnership include family involvement (i.e., family's inclusion in their child's care); family engagement (i.e., collaboration between TRC and families); family-driven (i.e., families as full partners). This review included thirty studies (n=23 family involvement, n=7 family engagement, n=0 family-driven). The most common family involvement methods were family therapy and family visits to the program, primarily delivered face-to-face. The most common family engagement method was activities, therapies, and skill building occurring at the home with family present. Methods of measuring family partnership primarily included the use of administrative data. Implications for research and practice include the provision of research that evaluates the effects of family partnership on outcomes important in the TRC setting and the development of research-practice and family-research collaborations to increase the uptake of effective family partnering methods.

Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986-2020.

BACKGROUND: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. METHODS: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. RESULTS: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years. CONCLUSIONS: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.

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.

Sexually transmitted infection knowledge among men who have sex with men in Nairobi, Kenya.

BACKGROUND: High rates of sexually transmitted infections (STIs) among men who have sex with men (MSM) have been reported, but there is little research on their STI knowledge. Our study sought to determine participants' characteristics that contribute to either high or low STI knowledge among MSM in Nairobi, Kenya. METHODS: We mobilized MSM aged ≥18 years from Nairobi into a cross-sectional study. To determine their understanding of STIs, a pre-tested structured questionnaire was administered. Knowledge score was generated by summing up the number of responses answered correctly by a participant. We dichotomized scores as "low" and "high", by splitting the group at <12 and ≥12 which was the mean. RESULTS: A total of 404 participants were interviewed between March and August 2020. The mean age was 25.2 (SD = 6.4) years. Majority were single (80.4%) and Christians (84.2%). All participants had some formal education ranging from primary to tertiary; the majority (92.3%) had secondary education or more. Most (64.0%) were employed and their monthly income ranged from <50->150 USD. Almost all (98.5%) were Kenyans. Of the 404 (90.6%) self-identified as male and (47.5%) reported to be exclusively top partners. Many (39.9%) reported being versatile, while those reporting to be bottom partners were, (12.6%). The last 12 months, (55.4%) of the participants reported having sex with men only and (88.6%) reported to have had multiple sexual partners. Participants scored an average of 12.2, SD 4.5. Multivariable backward elimination logistic regression revealed that participants who had tertiary education (aOR = 0.50, 95% CI 0.32-0.77), a higher income (aOR = 0.40, 95% CI 0.22-0.75) and were engaging in vaginal sex (aOR = 1.86, 95% CI 1.25-2.78) predicted significantly higher odds of high knowledge in the final multivariable model. CONCLUSION: Participant's knowledge level regarding STIs was low. We recommend health care workers to continue educating patients about STIs.

"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.

Proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses: A pilot study.

The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world. In particular, multiple countries in East, Central, and West Africa had significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, an exploratory study of stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n = 29) and from hospitalized Ugandan COVID-19 patients (n = 3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population, however this may be in part due to the limited sample size examined. The rates of cross-reactive T-cell populations in this exploratory Ugandan population appears higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.

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.

Acceptability and applicability of biometric iris scanning for the identification and follow up of highly mobile research participants living in fishing communities along the shores of Lake Victoria in Kenya, Tanzania, and Uganda.

BACKGROUND: Recruitment and retention of participants in research studies conducted in fishing communities remain a challenge because of population mobility. Reliable and acceptable methods for identifying and tracking participants taking part in HIV prevention and treatment research are needed. The study aims to assess the acceptability, and technical feasibility of iris scans as a biometric identification method for research participants in fishing communities. METHODS: This was a cross-sectional study conducted in eight fishing communities in Kenya, Tanzania, and Uganda, with follow-up after one month in a randomly selected subset of participants. All consenting participants had their iris scanned and then responded to the survey. RESULTS: 1,199 participants were recruited. The median age was 33 [Interquartile range (IQR) 24-42] years; 56% were women. The overall acceptability of iris scanning was 99%, and the success rate was 98%. Eighty one percent (n = 949) had a successful scan on first attempt, 116 (10%) on second and 113 (9%) after more than two attempts. A month later, 30% (n = 341) of participants were followed up. The acceptability of repeat iris scanning was 99% (n = 340). All participants who accepted repeat iris scanning had successful scans, with 307 (90%) scans succeeding on first attempt; 25 (7%) on second attempt, and 8 (2%) after several attempts. The main reason for refusing iris scanning was fear of possible side effects of the scan on the eyes or body. CONCLUSION: The acceptability and applicability of biometric iris scan as a technique for unique identification of research participants is high in fishing communities. However, successful use of the iris scanning technology in research will require education regarding the safety of the procedure.

High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses.

The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.

Factors Associated with Short and Long Term Mobility and HIV Risk of Women Living in Fishing Communities Around Lake Victoria in Kenya, Tanzania, and Uganda: A Cross Sectional Survey.

Mobility is linked to negative HIV care continuum outcomes. We sought to understand factors associated with short and long term mobility among women in fishing communities in Kenya, Tanzania, and Uganda. From 2018 through 2019 we conducted a cross-sectional survey of women aged 15 years and above, randomly selected from a census of six fishing villages, around Lake Victoria. Data collected included: demographics, risky sexual behaviour on the most recent trip, and travel behaviour in the previous 4 months. Mobility was recorded as any overnight trip outside the participant's village. A two-level multinomial logistic regression model was used to determine the associated factors. A total of 901 participants were enrolled, of whom 645 (71.6%) reported travelling (53.4%; short and 18.2% long term trips). Five factors were associated with long term travel: age, travel purpose, frequency of travel, sexual behaviour while travelling, and destination. Trips made by women aged 46-75 years were less likely to be long term. Long term trips were more common if the trip was to visit, rather than to trade, and more common for women who reported one or two trips rather than three or more trips. Women who made long term trips were more likely to engage in unprotected sex while on a trip. Women who travelled to a regional town/district or another town/district were more likely to take long term trips. The factors associated with travel duration among women living in fishing communities could inform planning of future health care interventions in these communities.

Assessment of a diverse panel of transmitted/founder HIV-1 infectious molecular clones in a luciferase based CD8 T-cell mediated viral inhibition assay.

Introduction: Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control. Methods: The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects. Results & discussion: CD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.

Feasibility of conducting HIV prevention trials among key populations in Nairobi, Kenya.

OBJECTIVE: To assess the feasibility of conducting HIV prevention trials among key populations in Nairobi, Kenya. BACKGROUND: HIV prevention trials require the inclusion of those at high risk of HIV infection and their informed decision to take part and remain in the clinical trial to the end is crucial. In Kenya key populations including men who have sex with men (MSM) and female sex workers (FSW) are, disproportionately, at high risk of HIV infection when compared to the general population. Few trials testing biomedical prevention products against HIV have enrolled Kenyan FSW and MSM. METHODS: We performed simulated vaccine efficacy trial (SiVET) using licensed hepatitis B vaccines as substitutes for a HIV vaccine candidate and included randomization for those immune to hep B. The SiVET was an observational study designed to mimic the rigors of a clinical trial; we assessed HIV risk, provided risk counselling and prevention tools and performed HIV testing at baseline and periodically until the end of the trial. MSM and FSW were enrolled at a ratio of 4:1. Volunteers were assigned to either hepatitis B vaccine or placebo. RESULTS: Recruitment took approximately 24 months between Sep 2015 and Sep 2017. Of the 368 volunteers screened, 250 (200 MSM and 50 FSW) were enrolled. Reasons for exclusion at screening included: being positive for HIV (n = 7), hepatitis (n = 14), other pre-existing medical conditions (n = 41), eligible but chose not to enrol (n = 47). Most of the volunteers adhered to study procedures and attended their study visits within the study window. These include volunteers who received the second vaccination 244 (98%), the third vaccination 228 (91%) and, the final study visit 217 (87%). The reasons volunteers discontinued from the study early included: relocation and loss to follow up (n = 14). A total of 8 cases of HIV infection were observed in 174.5 Person Years at Risk (PYAR), all among MSM, including 5 seroconversions identified at the last study visit, for a HIV incidence of 4.58 cases/ 100 PYAR, among MSM enrolled in the study. CONCLUSION: Our findings suggest that it is possible to conduct HIV prevention trials among key populations in Nairobi with a good adherence to a vaccine efficacy trial schedule. Despite HIV prevention efforts, we also noted a high incidence of HIV infection. This demonstrates the need for effective HIV prevention products in these populations.