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.

A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

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.

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 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.

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.

Evolution of Condom Use Among a 5-Year Cohort of Female Sex Workers in Zambia.

Observing sexual behaviour change over time could help develop behavioural HIV prevention interventions for female sex workers in Zambia, where these interventions are lacking. We investigated the evolution of consistent condom use among female sex workers and their clients and steady partners. Participants were recruited into an HIV incidence cohort from 2012 to 2017. At each visit, women received HIV counselling and testing, screening for sexually transmitted infections (STIs) and free condoms. Our outcome was reported consistent (100%) condom use in the previous month with steady partners, repeat clients, and non-repeat clients. Consistent condom use at baseline was highest with non-repeat clients (36%) followed by repeat clients (27%) and steady partners (17%). Consistent condom use between baseline and Month 42 increased by 35% with steady partners, 39% with repeat clients and 41% with non-repeat clients. Access to condoms, HIV/STI counselling and testing promoted positive sexual behaviour change.

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

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

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

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

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.

Evaluating the effectiveness of enhanced family planning education on knowledge and use of family planning in fishing communities of Lake Victoria in Uganda: a randomized controlled trial.

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 < 70% FP knowledge score was observed for all participants with a CPR of 36.8%. At month-12, the median FP knowledge score improved in both arms, higher in the intervention arm than the control arm (46 vs 30; p < 0.001). In the intervention arm, 304 (79.2%) had a score of ≥70 compared with 21 (5.5%) in the control arm (p < 0.001). In the negative binomial regression model, the change in FP knowledge score was 47% higher in the intervention arm than in the control arm (score ratio: 1.47, 95%CI: 1. 43-1.51, p < 0.001). The change in CPR was 16% higher in the intervention arm than in the control arm (Prevalence ratio: 1.16, 95%CI: 1.01-1.34, p < 0.040). INTERPRETATION: Enhanced FP education using a simplified FP education handout was more effective in increasing FP knowledge and use compared to routine FP counselling for people living in fishing communities. Innovative FP education interventions are recommended for improving FP knowledge and optimizing uptake in remote-rural settings where literacy levels are low. TRIAL REGISTRATION: The study was registered by the Pan African Clinical Trial Registry on 03 July 2021 with a Trial Registration Number PACTR202107891858045 . "Retrospectively registered".

Genital Abnormalities, Hormonal Contraception, and Human Immunodeficiency Virus Transmission Risk in Rwandan Serodifferent Couples.

BACKGROUND: We explored the role of genital abnormalities and hormonal contraception in human immunodeficiency virus (HIV) transmission among heterosexual serodifferent couples in Rwanda. METHODS: From 2002 to 2011, HIV-serodifferent couples who were not using antiretroviral treatment were followed up, and sociodemographic and clinical data were collected, family planning provided, and HIV-negative partners retested. Couples were assessed for genital ulcers; nonulcerative genital sexually transmitted infection (STIs), including gonorrhea, chlamydia, and trichomoniasis; and non-STI vaginal infections, including bacterial vaginosis and candida. Multivariable models evaluated associations between covariates and HIV transmission genetically linked to the index partner. RESULTS: Among 877 couples in which the man was HIV positive, 37 linked transmissions occurred. Factors associated with women's HIV acquisition included genital ulceration in the female partner (adjusted hazard ratio, 14.1) and nonulcerative STI in the male partner (8.6). Among 955 couples in which the woman was HIV positive, 46 linked transmissions occurred. Factors associated with HIV acquisition in men included nonulcerative STI in the female partner (adjusted hazard ratio, 4.4), non-STI vaginal dysbiosis (7.1), and genital ulceration in the male partner (2.6). Hormonal contraception use was not associated with HIV transmission or acquisition. CONCLUSIONS: Our findings underscore the need for integrating HIV services with care for genital abnormalities. Barriers (eg, cost of training, demand creation, advocacy, and client education; provider time; and clinic space) to joint HIV/STI testing need to be considered and addressed.

A Stronger Innate Immune Response During Hyperacute Human Immunodeficiency Virus Type 1 (HIV-1) Infection Is Associated With Acute Retroviral Syndrome.

BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n = 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.

Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis.

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.

Antiretroviral Therapy Use and HIV Transmission Among Discordant Couples in Nonresearch Settings in Kigali, Rwanda.

BACKGROUND: Antiretroviral therapy (ART) efficacy for HIV prevention among discordant couples has been demonstrated in clinical trials. Effectiveness outside of research settings is less well understood. METHODS: HIV-discordant couples were enrolled in couples' testing and follow-up at 20 government clinics in Kigali from 2010 to 2014. We performed viral linkage analysis on seroconverting couples to determine infection sources (intracouple vs. extracouple). Antiretroviral therapy use in index partners was collected at baseline and during follow-up by self-report with verification of government medical records. RESULTS: A total of 3777 HIV-discordant couples were identified and followed up at government health clinics. Fifty-four incident HIV infections were identified, of which 36 were confirmed linked to the index partner, 4 were unlinked, and 14 were unknown. Among the 50 linked or unknown transmission pairs, 38% occurred among couples in which the index partner was on ART (HIV incidence rate of 0.63/100 person-years), whereas 62% occurred among couples in which the index partner was not on ART (HIV incidence rate of 5.51/100 person-years; adjusted rate ratio, 6.9). HIV acquisition was higher in women than in men with non-ART using index partners (P < 0.001). CONCLUSIONS: Couples in a government clinic couples' HIV testing and follow-up program in Rwanda had an 89% reduction in HIV incidence when index partners were using ART, slightly lower than efficacy estimates from randomized trials. Antiretroviral therapy for prevention should be prioritized for key populations including discordant couples identified via couples' voluntary counseling and testing, with increased efforts to improve uptake, adherence, and viral load monitoring.

Developing and validating a risk algorithm to diagnose Neisseria gonorrhoeae and Chlamydia trachomatis in symptomatic Rwandan women.

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 < =25, having no/primary education, not having full-time employment, using condoms only sometimes, not reporting genital itching, testing negative for vaginal candida, and testing positive for bacterial vaginosis. The model was well calibrated (Hosmer-Lemeshow p = 0.831). Higher risk scores were significantly associated with increased prevalence of NG/CT infection (p < 0.001). Using a cut-point score of > = 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.

High risk sexual behaviours associated with traditional beliefs about gender roles among men interested in medical male circumcision in South Africa.

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/.

Hepatitis B prevalence and incidence in the fishing communities of Lake Victoria, Uganda: a retrospective cohort study.

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 < 0.01 and 1.4, 95% CI: 1.1-1.8; p < 0.01 respectively). CONCLUSION: Hepatitis B virus incidence in Lake Victoria fishing communities of Uganda is very high, particularly in the islands. Interventions to lower hepatitis B virus transmission in these communities are urgently needed.

Mobility for maternal health among women in hard-to-reach fishing communities on Lake Victoria, Uganda; a community-based cross-sectional survey.

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 .

Comparison of retention in observational cohorts and nested simulated HIV vaccine efficacy trials in the key populations in Uganda.

BACKGROUND: Outcomes in observational studies may not best estimate those expected in the HIV vaccine efficacy trials. We compared retention in Simulated HIV Vaccine Efficacy Trials (SiVETs) and observational cohorts drawn from two key populations in Uganda. METHODS: Two SiVETs were nested within two observational cohorts, one in Fisherfolk (FF) and another one in Female Sex Workers (FSW). Adult participants in each observational cohort were screened for enrolment into SiVETs. Those screened-out or not screened continued participation in the observational (non-SiVET) cohorts. SiVET participants were administered a licensed hepatitis B vaccine in a schedule that mimicked an actual HIV vaccine efficacy trial. Both cohorts were followed for 12 months and retention was assessed through dropout, defined as lost to follow up, being uncontactable, refusal to continue or missing the last study clinic visit. Dropout rates were compared using Poisson models giving rate ratios and 95% confidence intervals (95%CI). RESULTS: Out of 1525 participants (565 FF and 960 FSW), 572 (38%) were enrolled into SiVETs (282-FF and 290-FSW), and 953 (62%) remained in the non-SiVET cohorts. Overall, 326 (101 SiVET, 225 non-SiVET) dropped out in 1260 Person Years of Observation (PYO), a dropout rate of 25.9 /100 PYO (95%CI: 23.2-28.8); fewer dropped out in the SiVET cohorts (18.4, 95% CI: 15.1-22.4) than in the non-SiVET cohorts (31.6, 95% CI: 27.8-36.1), rate ratio (RR) =0.58, 95% CI: 0.46-0.73. In all cohorts, the dropout was more marked in FSW than in FF population. Duration lived in community was associated with dropout in both SiVETs and religion in both non-SiVET cohorts. CONCLUSION: The rate of dropout was lower in SiVET compared to non-SiVET cohort. Though the difference in dropout between SiVET and non-SiVET was generally similar, the actual dropout rates were higher in the FSW population. Conduct of SiVETs in these key populations could mean that designing HIV Vaccine Efficacy Trials will benefit from lower dropout rate shown in SiVET than non-SiVET observational cohort.

Comparison of HIV Risk Behaviors Between Clinical Trials and Observational Cohorts in Uganda.

Many key populations have high-risk behaviors for HIV infection making them suitable for HIV vaccine efficacy trials. However, these behaviors may change when participants enroll into a trial. We used HIV simulated vaccine efficacy trials (SiVETs) nested within observational cohorts of fisherfolks and female sex workers in Uganda to evaluate this difference. We screened observational cohort participants for enrolment into SiVETs, until 572 were enrolled. Those not enrolled (n = 953) continued participation in the observational cohorts. We determined risk behaviors at baseline and at 1 year, assigned a numeric score to each behavior and defined composite score as the sum of reported behaviors. We compared changes in scores over 12 months. Both observational cohorts and SiVETs saw a significant decrease in score but greatest in the SiVETs. Investigators recruiting for trials from these populations should consider the likely effect of reduction in risk behaviors on incident HIV infection and trial statistical power.

Clinical Characteristics and Long-Term Outcomes of Midaortic Syndrome.

BACKGROUND: Midaortic syndrome (MAS) is a rare congenital or acquired condition marked by segmental or diffuse stenosis of the distal thoracic and/or abdominal aorta and its branches. The optimal approach to medical or interventional management of MAS and long-term outcomes in adults are not well defined. We reviewed MAS cases to characterize the natural history of aortic disease, identify prognostic factors, and evaluate the durability of invasive interventions. METHODS: We conducted a retrospective review of patients with MAS who presented to Memorial Hermann Hospital and Baylor College of Medicine between 1997 and 2018. We categorized cases according to demographic and clinical manifestations, etiologies, the extent of aortic involvement, interventions, and vascular outcomes. RESULTS: We identified a cohort of 13 patients with MAS. The etiology of MAS was identified in 6 cases, including genetic syndromes (neurofibromatosis type 1 (2/13), Williams syndrome (1/13), fibromuscular dysplasia (2/13), and Takayasu arteritis (1/13)). Mean age at first documented clinical event was 25.2 (2-67) years, but cases with genetic etiologies presented significantly younger (18.2 years). The most common primary anatomic site was the suprarenal and infrarenal aorta (zones 5-8). Extra-aortic locations involved the renal (4/13), celiac (3/13), and superior mesenteric (3/13) arteries. Clinical manifestations included hypertension (13/13), claudication (9/13), and postprandial abdominal pain (5/13). All patients with available follow-up data underwent at least one surgical or endovascular intervention (range: 1-8). Postoperative complications included renal failure requiring postdischarge hemodialysis and respiratory failure. There were no deaths in long-term follow-up. CONCLUSIONS: MAS is a complex vasculopathy with substantial variability in clinical presentation and anatomic distribution. Extensive disease frequently requires multiple invasive interventions and results in refractory hypertension, which may predict subsequent clinical events. A multidisciplinary approach with long-term monitoring is essential for preservation of end-organ function and quality of life in this debilitating disease.