Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Incidence of Health Facility Switching and Associations With HIV Viral Rebound Among Persons on Antiretroviral Therapy in Uganda: A Population-based Study.

BACKGROUND: A substantial proportion of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their human immunodeficiency virus (HIV) care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. METHODS: We used data from 40 communities (2015-2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15-49 years with serologically confirmed HIV who self-reported ART use and contributed ≥1 follow-up visit were included. Facility switching and virologic outcomes were assessed between 2 consecutive study visits (ie, index and follow-up visits, interval of approximately 18 months). Those who reported different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. RESULTS: Overall, 2257 persons who self-reported ART use (median age, 35 years; 65% female, 92% initially suppressed) contributed 3335 visit-pairs and 5959 person-years to the analysis. Facility switching was common (4.8 per 100 person-years; 95% confidence interval [CI], 4.2-5.5) and most pronounced in persons aged <30 years and fishing community residents. Among persons suppressed at their index visit (n = 2076), incidence of viral rebound was more than twice as high in persons who switched facilities (adjusted incidence rate ratio = 2.27; 95% CI, 1.16-4.45). CONCLUSIONS: Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity.

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

BACKGROUND: Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). STUDY DESIGN AND METHODS: We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. RESULTS: Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. CONCLUSION: Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

Trends in Adolescent Human Papillomavirus Vaccination and Parental Hesitancy in the United States.

BACKGROUND: Human papillomavirus (HPV) vaccination coverage remains suboptimal in the United States, underscoring the importance of monitoring trends in vaccine hesitancy. METHODS: Cross-sectional data from the 2011-2020 National Immunization Survey-Teen were used to assess trends in HPV vaccination initiation among 13-17-year-olds, parental intent to initiate vaccination, and primary reasons for parental hesitancy. RESULTS: Among all sex and race and ethnicity groups, the prevalence of HPV vaccination initiation increased over time, but parental intent to vaccinate against HPV for unvaccinated teens remained consistently low (≤45%). Among hesitant parents, "safety concerns" increased in nearly all demographic groups, with the greatest increases observed for non-Hispanic white female and male teens and no change for non-Hispanic black female teens. In 2019-2020, parents of unvaccinated non-Hispanic white teens were least likely to intend on vaccinating their teens, and the most common reason for hesitancy varied by sex and race and ethnicity (eg, "safety concerns" for white teens and "not necessary" for black female teens). CONCLUSIONS: Although HPV vaccination initiation increased over time, a substantial fraction of parents remain hesitant, and trends in their reason varied by sex and race and ethnicity. Health campaigns and clinicians should address vaccine safety and necessity.

Adolescent vaccination against human papillomavirus (HPV) is a critical tool for cancer prevention. We analyzed trends in HPV vaccination initiation among adolescents aged 13­17 years and trends in parental hesitancy to initiate HPV vaccination for their teen, using data from a national survey in the United States. Between 2011­2012 and 2019­2020, adolescent HPV vaccination initiation increased over time for both female teens (from 53.4% to 75.2%) and male teens (from 14.5% to 71.5%). However, the majority of parents/guardians of unvaccinated teens did not intend to vaccinate their teen against HPV (ie, were vaccine hesitant), and this was consistent over time in all sex and race and ethnicity groups. Among hesitant parents, the proportion reporting safety concerns as their main reason for being hesitant increased over time in nearly all demographic groups, with the greatest increases in this reasoning observed for white teens. In 2019­2020, parents of unvaccinated white teens were most likely to be vaccine hesitant. The most common reason for being vaccine hesitant also differed by sex and race and ethnicity. Although HPV vaccination has been shown to be safe and effective, HPV vaccination coverage remains suboptimal, and a substantial fraction of parents/guardians continue to be hesitant to adolescent HPV vaccination.

Age Patterns of HSV-2 Incidence and Prevalence in Two Ugandan Communities: A Catalytic Incidence Model Applied to Population-Based Seroprevalence Data.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is an incurable sexually transmitted infection associated with increased risk of acquiring and transmitting human immunodeficiency virus (HIV). HSV-2 is highly prevalent in sub-Saharan Africa, but population-level estimates of incidence are sparse. METHODS: We measured HSV-2 prevalence from cross-sectional serological data among adults aged 18-49 years in 2 south-central Uganda communities (fishing, inland). We identified risk factors for seropositivity, then inferred age patterns of HSV-2 with a Bayesian catalytic model. RESULTS: HSV-2 prevalence was 53.6% (n = 975/1819; 95% confidence interval, 51.3%-55.9%). Prevalence increased with age, was higher in the fishing community, and among women, reaching 93.6% (95% credible interval, 90.2%-96.6%) by age 49 years. Factors associated with HSV-2 seropositivity included more lifetime sexual partners, HIV positive status, and lower education. HSV-2 incidence peakied at age 18 years for women and 19-20 years for men. HIV prevalence was up to 10-fold higher in HSV-2-positive individuals. CONCLUSIONS: HSV-2 prevalence and incidence were extremely high, with most infections occurring in late adolescence. Interventions against HSV-2, such as future vaccines or therapeutics, must target young populations. Remarkably higher HIV prevalence among HSV-2-positive individuals underscores this population as a priority for HIV prevention.

SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.

Dissolution of transactional sex relationships during COVID-19: a qualitative study of Ugandan men's experiences during COVID-19 lockdowns.

The COVID-19 pandemic and subsequent mitigation measures led to social disruption and negative economic shocks for a large proportion of Uganda's population. The social and economic consequences of COVID-19 on Ugandan men's sexual behaviours, including transactional sex relationships, are unclear. We conducted in-depth interviews between November 2021-February 2022 with 26 men in a high HIV prevalence region of Uganda. Data were analysed thematically to understand how sexual relationships, including transactional sex, were impacted by COVID-19. We found that COVID-19 mitigation measures had far-reaching social and economic impacts on most respondents, particularly those employed in the informal economy. Men described experiencing job loss, food insecurity and restricted mobility, which limited opportunities to provide for and meet with transactional sex partners. Inability to provide financial resources meant that men could not form new transactional sex relationships and men who could no longer provide for their existing transactional sex partners consistently reported relationship dissolution. Men who reported stable employment during the pandemic described few changes in transactional sex relationships. Similarly, men in non-transactional relationships did not report relationship dissolution despite decreased financial provision. Further research should assess the potential short- and long-term impacts of COVID-19 mitigation measures on transactional sex relationships.

Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study.

BACKGROUND: There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa. METHODS: Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression. RESULTS: There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15-29 vs 40-49 years; adjRR = 1.80; 95% CI = 1.19-2.71), male sex (adjRR = 2.09, 95% CI = 1.47-2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34-2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34-2.73) were factors associated with persistent viremia. CONCLUSIONS: Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

Seroprevalence of Chlamydia trachomatis Among Female Adults in the United States: The National Health and Nutrition Examination Surveys.

BACKGROUND: Chlamydia trachomatis is the most common nationally notifiable sexually transmitted infection in the United States; however, the seroprevalence of C. trachomatis infection is unknown. METHODS: This cross-sectional study was conducted among 1725 females aged 18 to 39 years who provided serum and urine samples in the 2013 through 2016 National Health and Nutrition Examination Surveys. Presence of anti-C. trachomatis Pgp3 immunoglobulin G (IgG) was determined using both an enzyme-linked immunosorbent assay (ELISA) and multiplex bead array (MBA). Weighted seroprevalence estimates were calculated. Correlates of seroprevalence were examined by multivariable Poisson regression. RESULTS: In 2013 through 2016, overall seroprevalence of C. trachomatis Pgp3 IgG was 30.0% (95% confidence interval [CI], 25.5-35.0) as measured by ELISA and 29.4% (95% CI, 25.8-33.0) as measured by the MBA assay. Overall agreement between tests was 87.1% (1503/1725). There was a high positive agreement by the MBA assay with current detection of chlamydia in urine (86% [36/42]), a past-year diagnosis of chlamydia (81.8% [27/33]), and a history of treatment for pelvic inflammatory disease (60.7% [37/61]). Seroprevalence of C. trachomatis Pgp3 IgG, as measured by MBA, was significantly higher among non-Hispanic Blacks (68.0%; adjusted prevalence ratio (aPR) = 2.7 [95% CI, 2.3-3.3]), Mexican Americans (30.9%; aPR = 1.5 [95% CI, 1.2-1.9]), and other Hispanics (35.0%; aPR = 1.9 [95% CI, 1.4-2.5]) compared with non-Hispanic Whites (21.4%). A higher lifetime number of sexual partners and a younger age at sexual debut was also associated with higher seroprevalence. CONCLUSION: Both the ELISA and MBA serologic assays revealed a high prevalence of antibodies to C. trachomatis Pgp3 in young adult females in the US household population. There were major racial/ethnic disparities in exposure to C. trachomatis, with increased vulnerability among non-Hispanic Black females.

Differential Performance of CoronaCHEK SARS-CoV-2 Lateral Flow Antibody Assay by Geographic Origin of Samples.

We assessed the performance of the CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Plasma samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive individuals (Uganda, 78 samples from 78 individuals, and Baltimore, 266 samples from 38 individuals) and from prepandemic individuals (Uganda, 1,077, and Baltimore, 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. After the first positive PCR in Ugandan samples, the sensitivity was 45% (95% confidence interval [CI], 24,68) at 0 to 7 days, 79% (95% CI, 64 to 91) at 8 to 14 days, and 76% (95% CI, 50 to 93) at >15 days. In samples from Baltimore, sensitivity was 39% (95% CI, 30 to 49) at 0 to 7 days, 86% (95% CI, 79 to 92) at 8 to 14 days, and 100% (95% CI, 89 to 100) at 15 days after positive PCR. The specificity of 96.5% (95% CI, 97.5 to 95.2) in Ugandan samples was significantly lower than that in samples from Baltimore, 99.3% (95% CI, 98.1 to 99.8; P < 0.01). In Ugandan samples, individuals with a false-positive result were more likely to be male (PR, 2.04; 95% CI, 1.03,3.69) or individuals who had had a fever more than a month prior to sample acquisition (PR, 2.87; 95% CI, 1.12 to 7.35). Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False-positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.

HIV Prevention Efforts and Incidence of HIV in Uganda.

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.

HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical "Brownian motion" model and another model ("Ornstein-Uhlenbeck") that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%-43%) is consistent with other studies based on regression of viral load in donor-recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.

Correction: Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.

[This corrects the article DOI: 10.1371/journal.pbio.2001855.].

Characteristics Associated With Human Immunodeficiency Virus Transmission Networks Involving Adolescent Girls and Young Women in Human Immunodeficiency Virus Prevention Trials Network 068 Study.

We combined behavioral survey data from the human immunodeficiency virus (HIV) Prevention Trials Network 068 study with phylogenetic information to determine if cluster membership was associated with characteristics of young women and their partners. Clusters were more likely to involve young women from specific villages and schools, indicating some localized transmission.Supplemental digital content is available in the text.

Increases in Human Papillomavirus Vaccination Among Adolescent and Young Adult Males in the United States, 2011-2016.

In the United States, human papillomavirus (HPV) vaccination has been recommended for females since 2006 and males since 2011. We assessed temporal trends in HPV vaccine coverage (defined as receipt of ≥1 dose) among 9-26-year-old participants in the 2011-2016 National Health and Nutrition Examination Surveys. While coverage increased overall, from 37.7% to 45.7%, among females (adjusted prevalence difference [aPD], 7.1%; 95% confidence interval [CI], .1%-13.7%), there was no change among female adolescents aged 9-17 years. For males, coverage increased overall, from 7.8% to 27.4% (aPD, 18.8%; 95% CI, 14.1%-23.5%), and among every stratum of age, race/ethnicity, health insurance status, poverty level, and immigration status (P ≤ .05). The increase in HPV vaccine coverage observed among males is encouraging, but coverage remains below national targets for both males and females.

Leveraging Ecological Momentary Assessment Data to Characterize Individual Mobility: Exploratory Pilot Study in Rural Uganda.

BACKGROUND: The geographical environments within which individuals conduct their daily activities may influence health behaviors, yet little is known about individual-level geographic mobility and specific, linked behaviors in rural low- and middle-income settings. OBJECTIVE: Nested in a 3-month ecological momentary assessment intervention pilot trial, this study aims to leverage mobile health app user GPS data to examine activity space through individual spatial mobility and locations of reported health behaviors in relation to their homes. METHODS: Pilot trial participants were recruited from the Rakai Community Cohort Study-an ongoing population-based cohort study in rural south-central Uganda. Participants used a smartphone app that logged their GPS coordinates every 1-2 hours for approximately 90 days. They also reported specific health behaviors (alcohol use, cigarette smoking, and having condomless sex with a non-long-term partner) via the app that were both location and time stamped. In this substudy, we characterized participant mobility using 3 measures: average distance (kilometers) traveled per week, number of unique locations visited (deduplicated points within 25 m of one another), and the percentage of GPS points recorded away from home. The latter measure was calculated using home buffer regions of 100 m, 400 m, and 800 m. We also evaluated the number of unique locations visited for each specific health behavior, and whether those locations were within or outside the home buffer regions. Sociodemographic information, mobility measures, and locations of health behaviors were summarized across the sample using descriptive statistics. RESULTS: Of the 46 participants with complete GPS data, 24 (52%) participants were men, 30 (65%) participants were younger than 35 years, and 33 (72%) participants were in the top 2 socioeconomic status quartiles. On median, participants traveled 303 (IQR 152-585) km per week. Over the study period, participants on median recorded 1292 (IQR 963-2137) GPS points-76% (IQR 58%-86%) of which were outside their 400-m home buffer regions. Of the participants reporting drinking alcohol, cigarette smoking, and engaging in condomless sex, respectively, 19 (83%), 8 (89%), and 12 (86%) reported that behavior at least once outside their 400-m home neighborhood and across a median of 3.0 (IQR 1.5-5.5), 3.0 (IQR 1.0-3.0), and 3.5 (IQR 1.0-7.0) unique locations, respectively. CONCLUSIONS: Among residents in rural Uganda, an ecological momentary assessment app successfully captured high mobility and health-related behaviors across multiple locations. Our findings suggest that future mobile health interventions in similar settings can benefit from integrating spatial data collection using the GPS technology in mobile phones. Leveraging such individual-level GPS data can inform place-based strategies within these interventions for promoting healthy behavior change.

Household transport ownership and HIV viral suppression in rural Uganda: a cross- sectional, population-based study.

Background: Empirical data on transportation access and HIV treatment outcomes in sub-Saharan Africa are rare. We assessed the association between household transport ownership and HIV viral suppression in rural Uganda. Methods: The study was conducted among people living with HIV aged 15-49 years using cross-sectional data from the Rakai Community Cohort Study (RCCS), collected from June 14, 2018, to November 6, 2020. Transport ownership was defined as household possession of a car, motorcycle, or bicycle. HIV viral suppression was defined as < 1000 HIV RNA copies/ml. Poisson regression with robust variance estimation identified unadjusted and adjusted prevalence ratios and 95% confidence intervals (CI) of HIV viral suppression by transport ownership. Results: The study included 3,060 persons aged 15-49 living with HIV. Overall HIV viral suppression was 86.5% and was higher among women compared to men (89.3% versus 81.6%; adjusted prevalence ratio: 1.14, 95% CI: 1.10, 1.18). A total of 874 participants (28.6%) resided in households that owned at least one means of transport. HIV viral suppression was 79.8% among men and 88.2% among women from households without any means of transport, compared to 85.4% among men and 92.4% among women from households with at least one means of transport. Adjusted prevalence ratios of HIV viral suppression were 1.11 (95% CI: 1.04, 1.18) for males and 1.06 (95% CI: 1.03, 1.10) for females from households owning at least one means of transport compared with those from households with none. Conclusion: There was increased HIV viral suppression among people living with HIV from households with transport means compared to those from households without transport means, suggesting transport may facilitate access to, and continued engagement with, HIV treatment services.

Pre-exposure prophylaxis (PrEP) knowledge, use, and discontinuation among Lake Victoria fisherfolk in Uganda: a cross-sectional population-based study.

Background: There are limited population-level data on the pre-exposure prophylaxis (PrEP) care continuum in eastern Africa. Here, we assessed the PrEP care continuum following PrEP rollout in a Ugandan community with ~40% HIV seroprevalence. Methods: We used cross-sectional population-based data collected between September 3 and December 19, 2018 from a Lake Victoria fishing community in southern Uganda to measure levels of self-reported PrEP knowledge, ever use, and discontinuation following 2017 PrEP rollout via a U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported phased implementation program. Our analysis included HIV-seronegative persons reporting having ever received an HIV test result. We examined associations between demographic, behavioral, and health utilization factors with each outcome using age-adjusted modified Poisson regression. Results: There were 1,401 HIV-seronegative participants, of whom 1,363 (97.3%) reported ever receiving an HIV test result. Median age was 29 years (IQR: 23-36), and 42.3% (n=577) were women. Most (85.5%; n=1,166) participants reported PrEP knowledge, but few (14.5%; n=197) reported ever using PrEP. Among 375 (47.7%) men and 169 (29.3%) women PrEP-eligible at time of survey, 18.9% (n=71) and 27.8% (n=47) reported ever using PrEP, respectively. Over half (52.3%, n=103) of those who had ever used PrEP, self-reported current use. Conclusion: In this Lake Victoria fishing community, there were low levels of PrEP use despite high levels of PrEP awareness and eligibility, particularly among men. Efforts that enhance awareness of HIV risk and increase PrEP accessibility may help increase PrEP use among HIV-seronegative persons in African settings with high HIV burden.

Increasing intra- and inter-subtype HIV diversity despite declining HIV incidence in Uganda.

HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.

Age and gender profiles of HIV infection burden and viraemia: novel metrics for HIV epidemic control in African populations with high antiretroviral therapy coverage.

Introduction: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating. Methods: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates. Results: Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets. Conclusions: The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.