Trevor A. Crowell

Background: Chlamydia and gonorrhea are common sexually transmitted infections (STIs) in populations with behavioral vulnerability to HIV. In Uganda, routine syndromic STI management underdiagnoses infections. Methods: Between October 2022 and September 2024, we enrolled participants in Kampala, Uganda, aged 14 to 55 years, without HIV, who reported a recent documented STI, injection drug use, transactional sex, condomless sex, or anal sex with males. Urine and anorectal/oropharyngeal swabs were tested for Chlamydia trachomatis and Neisseria gonorrhoeae (Xpert CT/NG, Cepheid). Multivariable robust Poisson regression with purposeful variable selection estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals for factors potentially associated with each STI. Results: Among 420 participants with a median age of 21 years (interquartile range 19–24), 241 (57.4%) were female, and 136 (32.4%) were males who have sex with men. Chlamydia was more prevalent than gonorrhea (21.9% vs 13.1%, P < 0.001). The anorectum was the most common site of infection with 75 chlamydia cases (17.9% [95% confidence interval 14.5%-21.8%]) and 51 gonorrhea cases (12.1% [9.4%–15.6%]), followed by the urogenital site with 45 chlamydia cases (10.7% [8.1%–14.0%]) and 23 gonorrhea cases (5.5% [3.7%–8.1%]). Urogenital-only screening would have missed 51.1% and 58.2% of chlamydia and gonorrhea cases, respectively, while urogenital + anorectal screening would have missed 1.1% and 0%. Male sex was independently associated with increased prevalence of chlamydia (aPR = 2.06 [1.37–3.11], P = 0.001) and gonorrhea (aPR 2.81 [1.56–5.06], P = 0.001). Chlamydia was also more common among participants aged 15 to 24 years compared with 25 to 40 (aPR = 2.11 [1.02–4.35], P = 0.043). Conclusions: Ugandan healthcare policies should consider anorectal chlamydia and gonorrhea testing, particularly among youth and males who have sex with men, to improve STI detection and reduce transmission.

Background: Human papillomavirus (HPV)‐associated cancers are preventable with vaccination. Serologic assays monitor antibody responses, but their complexity and cost pose limitations when evaluating population level immunity. We developed an L1‐based assay for the detection of multiple type‐specific HPV antibodies. Methods: The Luminex‐based assay used recombinant L1 proteins from seven HPVs (HPV‐6/11/16/18/35/45/58) for the detection of type‐specific immunoglobulin (Ig)G and IgA. Cutoffs were established using plasma from infants and children. The assay was optimized and qualified using a sample set from a blinded proficiency panel developed at the Frederick National Laboratory for Cancer Research. Results: Sensitivity and specificity for anti‐HPV‐6/11/16/18/58 IgG were 100% at the Mean + 3 standard deviation [SD] and Mean + 5 SD thresholds. Sensitivity for HPV‐45 was 100% and 92.9% at the +3 SD and +5 SD thresholds, respectively. IgA detection showed moderate positivity among vaccinated individuals, with peak estimates of 96.4% (HPV‐11) and 85.7% (HPV‐58) at the +3 SD threshold. IgA was correlated with IgG (Spearman's ρ = 0.74). The L1‐assay differentiated high, intermediate, low, and negative response groups from the blinded samples for all HPV genotypes ( p < 0.0001). Conclusion: The L1‐binding assay has the potential to be a scalable option for high‐throughput detection of broad‐spectrum HPV immunoglobulins, but further standardization and validation are needed.

Introduction: Adolescents and young adults living with HIV (AYLHIV) experience poor outcomes across the care continuum, and most reside in sub-Saharan Africa. The African Cohort Study (AFRICOS) provides an opportunity to examine HIV outcomes in this population across Kenya, Nigeria, Tanzania, and Uganda. Methods: We conducted a cross-sectional analysis of AYLHIV aged 15–29 years, enrolled in AFRICOS 2013-2023, and on antiretroviral therapy (ART) ≥ six months. Primary outcomes were HIV viremia and 30-day ART non-adherence. Factors included HIV acquisition route, ART duration, ART class, and site. We used multivariate robust Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). Site directors were surveyed to assess youth-friendly services. Results: Among 656 participants, the median age was 20.0 years (IQR 17.5–23.3); 41.6% were male, 61.6% had perinatally-acquired HIV, and median duration since HIV diagnosis was nine years. At enrollment, 83.8% had viral suppression (<200 copies/mL) and 80.2% were ART adherent. ART regimen and clinic site were associated with viral suppression: youth on integrase vs. protease inhibitor-based regimens (adjusted relative risk (aRR) 0.38, CI 0.23–0.63, p<0.001), and in Uganda (aRR 0.42, CI 0.20–0.90, p=0.026) or Kisumu, Kenya (aRR 0.40, CI 0.22–0.76, p=0.005) had lower likelihood of non-suppression. Compared to Nigeria, participants from other sites were less likely to report non-adherence (unadjusted RR 0.31-0.44). Youth-friendly service provision varied. Conclusions: Viral suppression and ART adherence were high among AYLHIV in AFRICOS. Clinic site and ART regimen were associated with outcomes, highlighting the importance of health system factors.

Background: Increasing multimorbidity among people with human immunodeficiency virus (PWH; HIV) in sub-Saharan Africa can result in hospitalization. We investigated longitudinal associations between multimorbidity trajectories and hospitalization risk within the African Cohort Study (AFRICOS). Methods: AFRICOS enrolls people with and without HIV from HIV clinics in Uganda, Kenya, Tanzania, and Nigeria. These analyses restricted PWH aged ≥18 years enrolled between 2013 and 2024. Multimorbidity (≥chronic conditions in addition to HIV) was ascertained from International Classification of Diseases codes and clinical measurements. Multimorbidity was categorized into 3 trajectories: resilient, developed, and continued. Hospitalization reasons were ascertained by medical record review. Andersen–Gill extensions of Cox proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association of multimorbidity trajectory and hospitalization. Results: Among 3028 PWH, 36.6% (n = 1109) had multimorbidity at enrollment. Over 17 740 person-years, 721 hospitalizations occurred (incidence density: 4.06 per 100 person-years). Systemic infections (n = 209, 29.0%), predominantly malaria (n = 182, 87.1%), led admissions. In adjusted models, PWH with continued multimorbidity had a significantly higher risk of hospitalization (aHR = 1.27, 95% CI: 1.06–1.53) compared with resilient PWH. Conclusions: PWH with continued multimorbidity have a significantly increased risk of hospitalization. Intervening early with optimal ART and comprehensive chronic disease management is critical for improving long-term outcomes in sub-Saharan Africa.

The era of highly effective pre-exposure prophylaxis (PrEP) has transformed HIV prevention, yet global HIV incidence remains unacceptably high, particularly in sub-Saharan Africa. While antiretroviral-based prevention is critical, persistent structural barriers to access and adherence highlight the urgent need for a complementary preventive HIV vaccine. In this narrative review and perspective, we argue that scientific progress toward an HIV vaccine must be matched by equally ambitious preparedness investments across three domains: manufacturing and supply chains, clinical trial and regulatory infrastructure, and delivery systems and community engagement. Drawing on lessons from the global rollout of PrEP, post-exposure prophylaxis (PEP), and the COVID-19 pandemic response, we outline a five-pillar strategic roadmap. This roadmap focuses on ensuring that a future HIV vaccine reaches the people who need it most from the moment of regulatory authorization, calling for co-investment in diverse platforms, binding advance market commitments, logistical simulation, and proactive planning for post-licensure effectiveness trials. Preparedness is not secondary to science; it is its essential partner.

Cognitive development in young adulthood among people living with HIV (PLWH) is not well understood, especially in the context of food insecurity (FI). Nutrient-based interventions may have unique cognitive benefits dependent on age and HIV status. Our analysis included participants enrolled in the African Cohort Study (AFRICOS). AFRICOS enrolls PLWH and without HIV (PLWoH) across 12 PEPFAR-supported facilities in Kenya, Nigeria, Tanzania, and Uganda. All participants were 15–27 years old and on antiretroviral therapy (ART) ≥ 6 months if PLWH. Annual neuropsychological assessments included the WHO Auditory Verbal Learning Test (AVLT; learning and memory), Trail Making Test Part A (TMT-A; processing speed), Color Trails 1 (CT1; processing speed), Color Trails 2 (CT2; executive functions), and Verbal Fluency (VF; language generativity). FI was determined by self-reporting not enough to eat or having < 3 meals per day. Linear mixed models assessed independent and interactive effects of age, HIV status, and time-varying FI on longitudinal cognitive outcomes. From 2013 to 2023 we collected data from 1,012 participants, of whom 575 (56.8%) were female and 476 (47.0%) ever FI. Overall, increasing age was associated with better cognitive performance. Despite ART experience, PLWH performed worse than PLWoH on language generativity (VF; β=-0.47, p = 0.032) and executive functions (CT2; β = 8.10, p = 0.004). FI was associated with worse memory performance at younger ages (β_FI*age = 0.17 [95%CI: 0.07, 0.27], p_FI*age=0.001) and poorer executive functions at older age (β_FI*age = 1.63 [95%CI: 0.56, 2.70], p_FI*age=0.003). Additional cognitive interventions may be needed for young PLWH including nutrient-based interventions that are developmentally tailored to unique cognitive domains.

Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are associated with morbidity in sub-Saharan Africa. Understanding the prevalence and demographic predictors of HBV co-infection among people living with HIV (PLWH) can inform integrated screening and treatment strategies. Methods: We analyzed enrollment data from the African Cohort Study (AFRICOS), a prospective study of participants aged ≥15 years with and without HIV across 12 clinical sites in Kenya, Uganda, Tanzania, and Nigeria. HBV was diagnosed via hepatitis B surface antigen (Bio-Rad, Hercules, CA). Descriptive statistics summarized HBV prevalence by HIV status and demographic characteristics. Relative risk (RR) of HBV among PLWH compared to people without HIV was calculated. Among PLWH, multivariable logistic regression identified odds ratios (ORs) and 95% confidence intervals (CIs) for factors independently associated with HBV co-infection. Results: Among 4,241 participants with valid HBV results, 3,439 were PLWH. HBV prevalence was 4.7% among PLWH and 4.2% among people without HIV (RR: 1.10; 95% CI: 0.77–1.59). Among PLWH, HBV prevalence was highest in Nigeria and lowest in Kenya (11.1% vs. 2.6%, p < 0.001), higher among males than females (6.7% vs. 3.2%, p < 0.001, and highest in participants aged ≥40 years and lowest in participants aged 15–19 years (5.8% vs. 0.2%, p < 0.001). In multivariable analysis, male sex (OR: 2.22 [95%CI: 1.59–3.09]), Nigeria residence (OR: 5.19 [95%CI: 3.35–8.05]), and age ≥ 40 (OR: 2.99 [95%CI: 1.74–5.13]) were independently associated with HBV co-infection. Conclusion: Routine HBV screening and targeted interventions are needed within HIV programs, especially for older males and in high-prevalence settings like Nigeria.

Future efficacy testing of candidate vaccines and other interventions to prevent HIV will require engagement of vulnerable populations. Here, we assessed willingness to participate in future clinical trials among participants recruited for an HIV incidence study in western Kenya. From February 2017 to May 2018, we recruited people living without HIV who reported multiple sexual partners into a 24-month HIV incidence cohort study in Kisumu County, Kenya. At screening for study eligibility and study exit, participants completed comprehensive sociobehavioral questionnaires. They were also provided a general definition of a clinical trial and asked if they would be willing to participate in a future clinical trial of a candidate HIV vaccine. At enrollment, participants were also asked about facilitators and barriers to participation in such a clinical trial. Among 940 individuals screened for enrollment into the HIV incidence study, 919 (97.8%) reported willingness to participate in a future clinical trial of a candidate HIV vaccine. Willing individuals were more likely than unwilling ones to have exchanged sex for goods or money (60.1% vs. 35.0%, p = 0.0237) and were less likely to believe that an individual's HIV status can be inferred by looking at them (8.7% vs. 23.8%, p = 0.0175). Willingness to participate was similarly common among participants who enrolled (608/618, 98.4%) and completed the study (518/533, 97.2%). The vast majority of the 618 enrolled participants reported obtaining HIV research information from radio/TV (n = 608, 98.1%) and newspapers/magazines/brochures (n = 579, 93.1%). Advantages they identified included HIV education (n = 594, 95.8%), access to healthcare (n = 576, 93.2%), and HIV counseling/testing (n = 574, 92.9%). Among 271 female participants, 235 (86.7%) identified free pregnancy testing as an advantage while 28 (19.4%) were unlikely to participate in a study that required the use of contraception. Among 10 enrollees who were unwilling to participate, five (50%) cited a fear of acquiring HIV and five (50%) cited fear of vaccine adverse effects. We identified a highly willing population for future testing of HIV preventive vaccines. Specific barriers to participation should be addressed in recruitment efforts.