Search

Abstract 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 a median age of 18 (IQR 17–18) years, 84.9% had less than secondary education, 48.4% had their sexual debut before 15 years, 47.1% reported paid sex in the past 3 months and 22.8% had a sexually transmitted infection (chlamydia, gonorrhea, and active syphilis) baseline characteristics associated with illicit drug use in the past 3 months were male gender (aOR 12.45; 95% CI 7.21–21.50) being married (aOR 2.26; 95%CI 1.03–4.94) 10 or more paying sexual partners (aOR 2.45; 95%CI 1.05–5.69) and high-risk alcohol use (aOR 3.94; 95%CI 2.10–7.40), baseline characteristics associated with high-risk alcohol use were male gender (aOR 0.29; 95% CI 0.13–0.63) emotional violence from sexual partners (aOR 2.35; 95%CI 1.32–418) illicit drug users com (aOR 3.94; 95% CI 2.10–7.40). Conclusion Illicit drug and high-risk alcohol use are prevalent among male adolescents and adolescents involved in high-risk sexual behavior living in the urban slums of Kampala.

Adolescents face a higher risk for HIV, STIs, and unintended pregnancy than any other age group in sub-Saharan Africa, and have unique health care needs as they navigate this period of growth and developmental milestones. We conducted the Youth Friendly Services study among adolescents in Rustenburg, South Africa to address some of these concerns. Participants aged 12-19 were followed quarterly for 12 months, asked at baseline about demographics, their sexual behavior, and tested for HIV, STIs, and pregnancy (girls). Report of sexual activity was not a requirement for enrollment. Assent and parental consent were obtained for participants under 18. Some follow up visits fell during COVID-mandated shutdowns, and we worked with participants to reschedule and extend follow up as appropriate. Here we present data on reported behaviors, participant attrition, risk of HIV, other STI, and pregnancy. From May 2018 to August 2019, we enrolled 223 HIV-negative, non-pregnant adolescents (64% girls). The median age was 17 (IQR: 14-18). Among the 119 (53%) participants who reported being sexually active at baseline, the median age at first sex was 16 years (IQR: 15-17). During follow-up, an additional 16 (7%) participants reported having their first sexual encounter. Among the sexually active participants, the incidence of HIV was 1.5 cases / 100 person-years at risk (PYAR, 95% CI: 0.4-6.0), the incidence of chlamydia was 15.7 cases (95% CI: 10.1-24.4), gonorrhea was 4.7 cases (95% CI: 2.1-10.5), and HSV was 6.3 cases (95% CI: 3.1-12.6); we observed no cases of incident syphilis. The incidence of pregnancy among sexually active girls was 15.0 pregnancies / 100 PYAR (95% CI: 8.5-26.5). Despite small numbers, the incidence of most STIs was significantly higher in females compared to males. We also observed two pregnancies and 5 incident STIs among participants who reported never having had sex, these tended to be younger participants. From March to September 2020, the clinic was shut down for COVID-19, and 53 study visits were postponed. Follow up was concluded in November 2020, a total of 19 participants were lost to follow up, however only one participant dropped off-study during COVID-19 shutdowns. Retention at the final visit was 91.5%. We successfully completed a prospective study of adolescents to learn more about the risks they face as they navigate sexual debut in the context of a program of youth-friendly counseling and services. Among self-reported sexually active participants, we observed a high rate of HIV, STI and pregnancy, however we also observed pregnancy and STIs among those who reported no sexual activity.

BackgroundAdolescent 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.MethodsWe 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.ResultsAll 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.ConclusionNon-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.

Abstract 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.

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.

Abstract 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.

BackgroundIn 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.MethodsWe 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.ResultsWe 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).ConclusionThe 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.

Abstract Introduction Family planning knowledge is poor and use is low in Ugandan fishing communities. We compared the effectiveness of enhanced family planning (FP) education with routine counselling on FP knowledge and use. Methods Individuals aged 15–49 years were randomly assigned to intervention or control arm. The intervention constituted enhanced FP education based on a simplified handout extracted from the WHO FP guidance tool called, “Family planning: A global handbook for FP providers” which participants took home for additional reading. The control arm constituted FP counselling following Uganda Ministry of Health guidelines. FP knowledge score and contraceptive prevalence rate (CPR) were compared between trial arms at baseline and at 12 months. Negative binomial regression models were used to estimate the effect of the intervention on FP knowledge and use. Results Overall, 1410 participants were screened to enrol 1004 (502 per study arm, 48.5% women). Subsequently, 384 (76.5%) and 383 (76.3%) completed the 12 months’ follow-up in the intervention and control arms respectively. At baseline, a median FP knowledge score of 8 and a

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.

BackgroundHigh 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.MethodsWe 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 ResultsA 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 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.ConclusionParticipant's knowledge level regarding STIs was low. We recommend health care workers to continue educating patients about STIs.

IntroductionImmunological 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.MethodsThe 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 & discussionCD4 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.

Measles is a vaccine-preventable viral disease whose vaccination coverage remains low in Zambia, where the target group for vaccination is children aged 9 to 18 months. In addition to inadequate measles vaccination coverage among children, few studies address potential resultant immunity gaps among adults. We analyzed data from a simulated HIV vaccine efficacy trial (SiVET) conducted from 2015–2017 among adult Zambian women of childbearing age to determine measles antibody seroprevalence before and after vaccination with the measles, mumps and rubella (MMR) vaccine. We used MMR vaccine as a substitute for an experimental HIV vaccine as part of a simulation exercise to prepare for an HIV vaccine efficacy trial. We found that 75% of women had measles antibodies prior to receiving MMR, which increased to 98% after vaccination. In contrast, mumps and rubella antibody prevalence was high before (93% and 97%, respectively) and after (99% and 100%, respectively) vaccination. The low baseline measles seropositivity suggests an immunity gap among women of childbearing age. We recommend that measles vaccination programs target women of childbearing age, who can pass antibodies on to neonates. Moreover, administering the MMR vaccine to clinical trial candidates could prevent measles, mumps or rubella-related adverse events during actual trials.

Abstract Background Maternal mortality is still a challenge in Uganda, at 336 deaths per 100,000 live births, especially in rural hard to reach communities. Distance to a health facility influences maternal deaths. We explored women’s mobility for maternal health, distances travelled for antenatal care (ANC) and childbirth among hard-to-reach Lake Victoria islands fishing communities (FCs) of Kalangala district, Uganda. Methods A cross sectional survey among 450 consenting women aged 15–49 years, with a prior childbirth was conducted in 6 islands FCs, during January-May 2018. Data was collected on socio-demographics, ANC, birth attendance, and distances travelled from residence to ANC or childbirth during the most recent childbirth. Regression modeling was used to determine factors associated with over 5 km travel distance and mobility for childbirth. Results The majority of women were residing in communities with a government (public) health facility [84.2 %, (379/450)]. Most ANC was at facilities within 5 km distance [72 %, (157/218)], while most women had travelled outside their communities for childbirth [58.9 %, (265/450)]. The longest distance travelled was 257.5 km for ANC and 426 km for childbirth attendance. Travel of over 5 km for childbirth was associated with adolescent girls and young women (AGYW) [AOR = 1.9, 95 % CI (1.1–3.6)], up to five years residency duration [AOR = 1.8, 95 % CI (1.0-3.3)], and absence of a public health facility in the community [AOR = 6.1, 95 % CI (1.4–27.1)]. Women who had stayed in the communities for up to 5 years [AOR = 3.0, 95 % CI (1.3–6.7)], those whose partners had completed at least eight years of formal education [AOR = 2.2, 95 % CI (1.0-4.7)], and those with up to one lifetime birth [AOR = 6.0, 95 % CI (2.0-18.1)] were likely to have moved to away from their communities for childbirth. Conclusions Despite most women who attended ANC doing so within their communities, we observed that majority chose to give birth outside their communities. Longer travel distances were more likely among AGYW, among shorter term community residents and where public health facilities were absent. Trial registration PACTR201903906459874 (Retrospectively registered). https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5977 .

Abstract Background Beliefs about gender roles and high-risk sexual behaviours underlie the human immunodeficiency virus (HIV) epidemic in South Africa. Yet, there is limited information on the relationships between beliefs about gender roles and risky sexual behaviours. Few studies have explored the association between beliefs about gender roles, high risk sexual behaviour, and health-seeking behaviour among men. Methods We investigated associations between gender beliefs (dichotomised as traditional or progressive) and high-risk sexual behaviour among South African men presenting for medical male circumcision (Apr 2014 to Nov 2015). Results Of 2792 enrolled men, 47.4% reported traditional gender beliefs. Participant ages ranged between 18–46 years (median age 26 years; interquartile range, 21–31 years). Most participants had at least one sex partner over the last 12 months (68.2%). Younger men (18–24 years old vs. 25–46 years old) (odds ratio [OR], 1.5 [95% confidence interval (CI) 1.0–2.0]), those with multiple partners ([OR], 1.5 (CI) 1.3–1.8]) and participants unsure of their last partner’s HIV status (OR, 1.4 [95% CI 1.1–1.7]) were more likely to have traditional beliefs on gender roles. Conclusion Young men with traditional beliefs on gender roles may be more likely to engage in high-risk sexual behaviour and could be good candidates for HIV prevention programmes. N = 206 (max 350) Trial registration Name of registry: Clinicaltrials.gov; Trial registration number: NCT02352961; Date of registration: 30 January 2015 “Retrospectively registered”; URL of trial registry record: https://www.clinicaltrials.gov/

Objectives: To explore whether community health worker household-based maternal health visits improve antenatal care and skilled birth attendance among hard-to-reach fishing villages on Lake Victoria, Uganda. Methods: This quasi-experimental 18-month prospective study involved 486 consenting women aged 15–49 years, who were pregnant or had a pregnancy outcome in the past 6 months, from 6 island fishing communities. The community health worker household-based intervention (community health workers’ household visits to provide counseling, blood pressure measurement, anemia, and HIV testing) involved 243 women from three fishing communities. Random effects logistic regression was used to determine the association between the community health worker intervention and antenatal care and skilled birth attendance among women who had at least 5 months of pregnancy or childbirth at follow-up. Results: Almost all women accepted the community health worker intervention (90.9% (221/243)). Hypertension was at 12.5% (27/216) among those who accepted blood pressure measurements, a third (33.3% (9/27)) were pregnant. HIV prevalence was 23.5% (52/221). Over a third (34.2% (69/202)) of women tested had anemia (hemoglobin levels less than 11 g/dL). The community health worker intervention was associated with attendance of first antenatal care visit within 20 weeks of pregnancy (adjusted odd ratio = 2.1 (95% confidence interval 0.6–7.6)), attendance of at least four antenatal care visits (adjusted odd ratio = 0.9 (95% confidence interval 0.4–2.0)), and skilled birth attendance (adjusted odd ratio = 0.5 (95% confidence interval 0.1–1.5)), though not statistically significant. Conclusion: Community health workers have a crucial role in improving early antenatal care attendance, early community-based diagnosis of anemia, hypertensive disorders, and HIV among women in these hard-to-reach fishing communities.

Gender-based violence (GBV) toward women is widespread and has been associated with increased HIV risk. We investigated attitudes toward GBV among men living in Rustenburg, South Africa, who were enrolled in a longitudinal HIV incidence study. Participants were 18 to 49 years old, reported high risk sexual activity in the last 3 months, and were HIV-uninfected. Attitudes toward GBV were evaluated using responses to a five-item standardized questionnaire about men perpetrating physical violence on a female spouse; responses to each item were scaled from 1 ( no agreement ) to 4 ( strong agreement ) and summed. Total scores >10 were considered permissive toward GBV. Among the 535 men analyzed, nearly half ( N = 229, 42.8%) had a GBV score >10. Being young (18–24 years) (adjusted odds ratio [aOR] = 1.53, 95% confidence interval [CI] [1.06, 2.22]), having less years of education (aOR = 1.61, 95% CI [1.11, 2.32]), and reporting no current sexual partner at baseline (aOR = 2.10, 95% CI [1.06, 4.14]) were independently associated with permissive attitudes toward GBV. The following behaviors reported in the last 3 months were also associated with high GBV scores: having a new female partner (aOR = 1.78, 95% CI [1.02, 3.10]), and having had an STI (aOR = 1.85, 95% CI [1.15, 2.99]). Consuming alcohol prior to sex in the last month (aOR = 1.59, 95% CI [1.09, 2.31]) was also associated with high GBV scores. A large proportion of South African HIV-uninfected men in this analysis reported permissive attitudes toward GBV. These attitudes were associated with HIV risk behavior. Integrating GBV and HIV prevention programs is essential.

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA/MVA/protein immunization protocol, 10 RM were immunized with each T/F Env. Within each T/F Env group, the protein boosts were administered as either monomeric gp120 or stabilized trimeric gp140 protein. All vaccination regimens elicited high titers of antigen-specific IgG, and two animals that received monomeric Z1800M Env gp120 developed autologous neutralizing activity. Using early Env escape variants isolated from subject Z1800M as guides, the serum neutralizing activity of the two immunized RM was found to be dependent on the gp120 V5 region. Interestingly, the exact same residues of V5 were also targeted by a neutralizing monoclonal antibody (nmAb) isolated from the subject Z1800M early in infection. Glycan profiling and computational modeling of the Z1800M Env gp120 immunogen provided further evidence that the V5 loop is exposed in this T/F Env and was a dominant feature that drove neutralizing antibody targeting during infection and immunization. An expanded B cell clonotype was isolated from one of the neutralization-positive RM and nmAbs corresponding to this group demonstrated V5-dependent neutralization similar to both the RM serum and the human Z1800M nmAb. The results demonstrate that neutralizing antibody responses elicited by the Z1800M T/F Env in RM converged with those in the HIV-1 infected human subject, illustrating the potential of using immunogens based on this or other T/F Envs with well-defined immunogenicity as a starting point to drive breadth.

Abstract Background Algorithms that bridge the gap between syndromic sexually transmitted infection (STI) management and treatment based in realistic diagnostic options and local epidemiology are urgently needed across Africa. Our objective was to develop and validate a risk algorithm for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) diagnosis among symptomatic Rwandan women and to compare risk algorithm performance to the current Rwandan National Criteria for NG/CT diagnosis. Methods The risk algorithm was derived in a cohort (n = 468) comprised of symptomatic women in Kigali who sought free screening and treatment for sexually transmitted infections and vaginal dysbioses at our research site. We used logistic regression to derive a risk algorithm for prediction of NG/CT infection. Ten-fold cross-validation internally validated the risk algorithm. We applied the risk algorithm to an external validation cohort also comprised of symptomatic Rwandan women (n = 305). Measures of calibration, discrimination, and screening performance of our risk algorithm compared to the current Rwandan National Criteria are presented. Results The prevalence of NG/CT in the derivation cohort was 34.6%. The risk algorithm included: age = 5, the risk algorithm had a sensitivity of 81%, specificity of 54%, positive predictive value (PPV) of 48%, and negative predictive value (NPV) of 85%. Internal and external validation showed similar predictive ability of the risk algorithm, which outperformed the Rwandan National Criteria. Applying the Rwandan National Criteria cutoff of > = 2 (the current cutoff) to our derivation cohort had a sensitivity of 26%, specificity of 89%, PPV of 55%, and NPV of 69%. Conclusions These data support use of a locally relevant, evidence-based risk algorithm to significantly reduce the number of untreated NG/CT cases in symptomatic Rwandan women. The risk algorithm could be a cost-effective way to target treatment to those at highest NG/CT risk. The algorithm could also aid in sexually transmitted infection risk and prevention communication between providers and clients.

Abstract 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.

Abstract Introduction Hepatitis B is a serious potentially fatal hepatocellular disease caused by the hepatitis B virus. In the fishing communities of Lake Victoria Uganda, the hepatitis B virus infection burden is largely unknown. This study assessed the prevalence and incidence of hepatitis B in these communities. Methods This was a retrospective cohort study that tested serum samples collected from 13 to 49-year-old study participants that were residing in two Ugandan Lake Victoria fishing communities of Kasenyi (a mainland) and Jaana (an island). The samples were collected between 2013 and 2015 during the conduct of an HIV epidemiological cohort study in these communities. A total of 467 twelve-month follow-up and 50 baseline visit samples of participants lost to follow-up were tested for hepatitis B serological markers to determine prevalence. To determine hepatitis B virus incidence, samples that were hepatitis B positive at the follow-up visit had their baseline samples tested to identify hepatitis B negative samples whose corresponding follow-up samples were thus incident cases. Results The baseline mean age of the 517 study participants was 31.1 (SD ± 8.4) years, 278 (53.8%) of whom were females. A total of 36 (7%) study participants had hepatitis B virus infection, 22 (61.1%) of whom were male. Jaana had a higher hepatitis B virus prevalence compared to Kasenyi (10.2% vs 4.0%). In total, 210 (40.6%) study participants had evidence of prior hepatitis B virus infection while 48.6% had never been infected or vaccinated against this disease. A total of 20 (3.9%) participants had results suggestive of prior hepatitis B vaccination. Hepatitis B incidence was 10.5 cases/100PY (95% CI: 7.09–15.53). Being above 25 years of age and staying in Jaana were significant risk factors for hepatitis B virus acquisition (AOR 1.6, 95% CI: 1.1–2.2; p

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.

HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial pol sequences sampled during 2006–2019 from MSM in Coast (N = 178, 47.9%), Nairobi (N = 137, 36.8%), and Nyanza (N = 57, 15.3%) provinces in Kenya. Maximum-likelihood (ML) phylogenetics and Bayesian inference were used to determine HIV-1 clusters, evolutionary dynamics, and virus migration rates between geographic regions. HIV-1 sub-subtype A1 (72.0%) was most common followed by subtype D (11.0%), unique recombinant forms (8.9%), subtype C (5.9%), CRF 21A2D (0.8%), subtype G (0.8%), CRF 16A2D (0.3%), and subtype B (0.3%). Forty-six clusters (size range 2–20 sequences) were found—half (50.0%) of which had evidence of extensive HIV-1 mixing among different provinces. Data revealed an exponential increase in infections among MSM during the early-to-mid 2000s and stable or decreasing transmission dynamics in recent years (2017–2019). Phylogeographic inference showed significant (Bayes factor, BF > 3) HIV-1 dissemination from Coast to Nairobi and Nyanza provinces, and from Nairobi to Nyanza province. Strengthening HIV-1 prevention programs to MSM in geographic locations with higher HIV-1 prevalence among MSM (such as Coast and Nairobi) may reduce HIV-1 incidence among MSM in Kenya.

Abstract Background When integrated with couples’ voluntary HIV counselling and testing (CVCT), family planning including long acting reversible contraceptives (LARC) addresses prongs one and two of prevention of mother-to-child transmission (PMTCT). Methods In this observational study, we enrolled equal numbers of HIV concordant and discordant couples in four rural and four urban clinics, with two Catholic and two non-Catholic clinics in each area. Eligible couples were fertile, not already using a LARC method, and wished to limit or delay fertility for at least 2 years. We provided CVCT and fertility goal-based family planning counselling with the offer of LARC and conducted multivariate analysis of clinic, couple, and individual predictors of LARC uptake. Results Of 1290 couples enrolled, 960 (74%) selected LARC: Jadelle 5-year implant (37%), Implanon 3-year implant (26%), or copper intrauterine device (IUD) (11%). Uptake was higher in non-Catholic clinics (85% vs. 63% in Catholic clinics, p

Region-specific laboratory reference intervals (RIs) are important for clinical trials and these data are often sparse in priority areas for research, including Africa. We reviewed data on RIs from Africa to identify gaps in the literature with a systematic review of PubMed for RI studies from Africa published ≥2010. Search focus included clinical analytic chemistry, hematology, immunological parameters and RIs. Data from adults, adolescents, children, pregnant women, and the elderly were included. We excluded manuscripts reporting data from persons with conditions that might preclude clinical trial participation in studies enrolling healthy volunteers. Of 179 identified manuscripts, 80 were included in this review, covering 20 countries with the largest number of studies in Ethiopia (n = 23, 29%). Most studies considered healthy, nonpregnant adults (n = 55, 69%). Nine (11%) studies included pregnant women, 13 (16%) included adolescents and 22 (28%) included children. Recruitment, screening, enrollment procedures and definition of age strata varied across studies. The most common type of RIs reported were hematology (66, 83%); 14 studies (18%) included flow cytometry and/or T cell counts. Other common tests or panels included liver function assays (32, 40%), renal function assays (30, 38%), lipid chemistries (17, 21%) and serum electrolytes (17, 21%). The number of parameters characterized ranged from only one (three studies characterized either CD4+ counts, D-dimer, or hemoglobin), to as many as 40. Statistical methods for calculating RIs varied. 56 (70%) studies compared their results to international RI databases. Though most presented their data side-by-side with international data with little accompanying analysis, nearly all reported deviation from comparator RI data, sometimes with half or more of otherwise healthy participants having an "out of range" result. We found there is limited local RI data available in sub-Saharan Africa. Studies to fill this gap are warranted, including efforts to standardize statistical methods to derive RIs, methods to compare with other RIs, and improve representative participant selection.

# Background Progress in reducing malaria incidence and deaths has stalled, in part due to limited access to quality malaria testing and treatment amongst rural populations. This time-series analysis aims to describe changes in rural malaria diagnosis and treatment before and during the rollout of Liberia’s National Community Health Assistant (CHA) program. It also explores how malaria service delivery changed during the COVID-19 epidemic. # Methods Malaria diagnosis and treatment data from 315 rural health facility catchments supported by Liberia’s National CHA Program were collected from Liberia’s Health Management Information System and analyzed. Trends in malaria service delivery coverage and quality were assessed between January 2011 and December 2020. # Results By 2020, four years after the program’s introduction, Liberia’s Community Health Assistants diagnosed 50% of rapid diagnostic test (RDT) or microscopy-confirmed malaria cases and carried out 51% of malaria treatments amongst children under age five in rural areas where CHAs were present. Furthermore, the percentage of malaria diagnoses that were confirmed by microscopy or RDT increased from 71% prior to the program to 95% in 2020. These results were effectively sustained in rural and remote communities during COVID-19 in 2020. # Conclusions The introduction of Liberia’s CHA program was associated with improvements in the quality of malaria diagnoses and contributed to treating a significant share of the malaria burden amongst children under age five in remote rural communities across Liberia, and these improvements were sustained during COVID-19. Investments made in rural community health systems can be leveraged by policy makers to strengthen malaria diagnosis, treatment and control, especially in the age of COVID-19.

IntroductionThe longstanding inadequacies of syndromic management for genital ulceration and inflammation are well-described. The Rwanda National Guidelines for sexually transmitted infection (STI) syndromic management are not yet informed by the local prevalence and correlates of STI etiologies, a component World Health Organization guidelines stress as critical to optimize locally relevant algorithms.MethodsRadio announcements and pharmacists recruited symptomatic patients to seek free STI services in Kigali. Clients who sought services were asked to refer sexual partners and symptomatic friends. Demographic, behavioral risk factor, medical history, and symptom data were collected. Genital exams were performed by trained research nurses and physicians. We conducted phlebotomy for rapid HIV and rapid plasma reagin (RPR) serologies and vaginal pool swab for microscopy of wet preparation to diagnose Trichomonas vaginalis (TV), bacterial vaginosis (BV), and vaginal Candida albicans (VCA). GeneXpert testing for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were conducted. Here we assess factors associated with diagnosis of NG and CT in men and women. We also explore factors associated with TV, BV and VCA in women. Finally, we describe genital ulcer and RPR results by HIV status, gender, and circumcision in men.ResultsAmong 974 men (with 1013 visits), 20% were positive for CT and 74% were positive for NG. Among 569 women (with 579 visits), 17% were positive for CT and 27% were positive for NG. In multivariate analyses, factors associated with CT in men included younger age, responding to radio advertisements, 1 partner was associated with BV; being single and RPR+ was associated with TV; and having < = 1 partner in the last month, being pregnant, genital itching, discharge, and being HIV and RPR negative were associated with VCA. Genital ulcers and positive RPR were associated with being HIV+ and lack of circumcision among men. HIV+ women were more likely to be RPR+. In HIV+ men and women, ulcers were more likely to be herpetic rather than syphilitic compared with their HIV- counterparts.ConclusionsSyndromic management guidelines in Rwanda can be improved with consideration of the prevalence of confirmed infections from this study of symptomatic men and women representative of those who would seek care at government health centers. Inclusion of demographic and risk factor measures shown to be predictive of STI and non-STI dysbioses may also increase diagnostic accuracy.

ObjectiveTo evaluate factors associated with willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.BackgroundWorking with 'key populations', those at elevated risk of HIV acquisition, is important to conduct efficient HIV prevention trials. In Nairobi Kenya, HIV infection is higher in men who have sex with men (MSM) and female sex workers (FSW) than in the general adult population, hence the need to establish if they would be willing to participate in future HIV vaccine trials.MethodsWe administered a structured questionnaire to MSM and FSW enrolled in a simulated vaccine efficacy trial (SiVET). The SiVET was an observational study designed to mimic the rigors of a clinical trial to assess HIV risk characteristics at baseline. After 12-15 months of follow-up, a structured questionnaire was administered to evaluate hypothetical willingness to participate in future HIV vaccine trials.ResultsOf 250 persons (80% MSM by design) enrolled in SiVET, 214 attended the final study visit and 174 (81%) of them expressed hypothetical willingness to participate in future HIV vaccine trials. These were 82% of MSM and 80% of FSW of those who attended the final study visit. Having a very good experience in the SiVET trial predicted willingness to participate in future HIV vaccine trials. Motivating factors for participation included a desire to receive education about HIV (59%) and to receive healthcare (57%).ConclusionsOur data demonstrate high willingness among key populations in Kenya, to participate in future HIV vaccine trials after completing participation in a SiVET. The findings suggest that these groups might be a reliable target population for consideration in future HIV vaccine trials. Assessment of willingness to participate in these populations provides important information that may help to inform future education and recruitment efforts for vaccine trials. Improving the research experience for members of key populations could impact their willingness to participate in HIV vaccine trials.

Despite extensive research on the mechanisms of HLA-mediated immune control of HIV-1 pathogenesis, it is clear that much remains to be discovered, as exemplified by protective HLA alleles like HLA-B*81 which are associated with profound protection from CD4+ T cell decline without robust control of early plasma viremia. Here, we report on additional HLA class I (B*1401, B*57, B*5801, as well as B*81), and HLA class II (DQB1*02 and DRB1*15) alleles that display discordant virological and immunological phenotypes in a Zambian early infection cohort. HLA class I alleles of this nature were also associated with enhanced immune responses to conserved epitopes in Gag. Furthermore, these HLA class I alleles were associated with reduced levels of lipopolysaccharide (LPS) in the plasma during acute infection. Elevated LPS levels measured early in infection predicted accelerated CD4+ T cell decline, as well as immune activation and exhaustion. Taken together, these data suggest novel mechanisms for HLA-mediated immune control of HIV-1 pathogenesis that do not necessarily involve significant control of early viremia and point to microbial translocation as a direct driver of HIV-1 pathogenesis rather than simply a consequence.

BackgroundPoint of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically reviewed evidence of POC test performance compared to laboratory-based HIV-1 RNA assays and the potential utility of these tests for diagnosis and care in RLS.MethodsStudies published up to July 2018 were identified by a search of PUBMED, EMBASE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. Studies evaluating the use of POC HIV-1 RNA testing for early infant diagnosis (EID), acute HIV infection (AHI) diagnosis, or viral load monitoring (VL), compared to centralized testing, were included. Separate search strategies were used for each testing objective.Results197 abstracts were screened and 34 full-text articles were assessed, of which 32 met inclusion criteria. Thirty studies evaluated performance and diagnostic accuracy of POC tests compared to standard reference tests. Two of the thirty and two additional studies with no comparative testing reported on clinical utility of POC results. Five different POC tests (Cepheid GeneXpert HIV-1 Quantitative and Qualitative assays, Alere q HIV-1/2 Detect, SAMBA, Liat HIV Quant and Aptima HIV-1 Quant) were used in 21 studies of VL, 11 of EID and 2 of AHI. POC tests were easy to use, had rapid turnaround times, and comparable accuracy and precision to reference technologies. Sensitivity and specificity were high for EID and AHI but lower for VL. For VL, lower sensitivity was reported for whole blood and dried blood spots compared to plasma samples. Reported error rates for Cepheid GeneXpert Qual (2.0%-5.0%), GeneXpert Quant (2.5%-17.0%) and Alere q HIV-1/2 Detect (3.1%-11.0%) were higher than in WHO prequalification reports. Most errors resolved with retesting; however, inadequate sample volumes often precluded repeat testing. Only two studies used POC results for clinical management, one for EID and another for VL. POC EID resulted in shorter time-to-result, rapid ART initiation, and better retention in care compared to centralised testing.ConclusionsPerformance of POC HIV-1 RNA tests is comparable to reference assays, and have potential to improve patient outcomes. Additional studies on implementation in limited-resources settings are needed.

IntroductionPeople living in fishing communities around Lake Victoria may be suitable for enrolment in HIV prevention trials because of high HIV incidence. We assessed the ability to recruit and retain individuals from fishing communities into an HIV vaccine preparedness cohort study in Masaka, Uganda.MethodsHIV high risk, sero-negative adults (18-49 years) were identified from four fishing villages bordering Lake Victoria through door-to-door HIV counselling and testing (HCT). Interested persons were referred for screening, enrolment, and quarterly follow-up visits at a study clinic located approximately 30-40 kilometres away. Repeat HCT, HIV risk assessment, and evaluation and treatment for sexually transmitted infections were provided. Rates of and factors associated with study dropout were assessed using Poisson regression models.ResultsA total of 940 participants were screened between January 2012 and February 2015, of whom 654 were considered for the analysis. Over a two-year follow-up period, 197 (30.1%) participants dropped out of the study over 778.9 person-years, a dropout rate of 25.3 / 100 person-years of observation. Dropout was associated with being female (aRR = 1.56, 95% confidence interval [CI] 1.12-2.18), being 18-24 years (aRR = 1.64; 95% CI 1.03-2.60) or being 25-34 years (aRR = 1.63; 95% CI 1.04-2.55) compared to being 35+ years; having no education (aRR = 2.02; 95% CI: 1.23-3.31); living in the community for less than one year (aRR = 2.22; 95% CI: 1.46-3.38), or 1-5 years (aRR = 1.68; 95% CI: 1.16-2.45), compared to more than five years.ConclusionsOur results suggest that individuals from fishing communities can be recruited and retained in longitudinal studies; however, intensified participant tracing may be necessary for women, younger volunteers, those who are less educated and new residents.

BACKGROUND:Fever is common among patients seeking care in sub-Saharan Africa (sSA), but causes other than malaria are rarely diagnosed. We assessed dengue and chikungunya virus infections among young febrile adults evaluated for acute HIV infection (AHI) and malaria in coastal Kenya. METHODS:We tested plasma samples obtained in a cross-sectional study from febrile adult patients aged 18-35 years evaluated for AHI and malaria at urgent care seeking at seven health facilities in coastal Kenya in 2014-2015. Dengue virus (DENV) and chikungunya virus (CHIKV) were amplified using quantitative real-time reverse-transcription polymerase chain reaction. We conducted logistic regression analyses to determine independent predictors of dengue virus infection. RESULTS:489 samples that were negative for both AHI and malaria were tested, of which 43 (8.8%, 95% confidence interval [CI]: 6.4-11.7) were positive for DENV infection. No participant was positive for CHIKV infection. DENV infections were associated with clinic visits in the rainy season (adjusted odds ratio (AOR) = 3.0, 95% CI: 1.3-6.5) and evaluation at a private health facility (AOR 5.2, 95% CI: 2.0-13.1) or research health facility (AOR = 25.6, 95% CI: 8.9-73.2) instead of a public health facility. CONCLUSION:A high prevalence of DENV infections was found in febrile young adult patients evaluated for AHI. Our data suggests that DENV, along with AHI and malaria, should be considered in the differential diagnosis of the adult patient seeking care for fever in coastal Kenya.

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.