The intersection between migration, HIV, and contraceptive use in Uganda: a cross-sectional population-based study.

BACKGROUND: Low use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use. METHODS: We analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand. RESULTS: There were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (± 8) years, and 17.3% (n = 591) were living with HIV. Overall, 43.9% (n = 1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR] = 1.14; 95% confidence interval [95%CI]: 1.02-1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR = 0.80; 95%CI = 0.70-0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant. CONCLUSIONS: Unsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.

Through a cross-sectional study, we explored the relationship between HIV status, migration, and contraceptive use among sexually active women of reproductive age in rural south-central Uganda. People who had moved into the study area within the last 1.5 years were considered in-migrants, compared to long-term residents i.e. people who had not moved. We examined unsatisfied demand for a modern contraceptive method, which is to say female participants who did not want to become pregnant in the next 12 months and were not using at least one of the following contraceptive methods: injectable, oral pill, implant, or condom. We included 3,417 sexually active female participants with no intention of becoming pregnant in the next year. The average age of these women was 30 years, less than 20% were living with HIV, and almost half were not using any modern contraceptive methods. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents, whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-negative participants. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand. This study shows the need for integrating contraceptive and HIV services for mobile populations in East Africa.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Phylogenetic Analysis of Human Immunodeficiency Virus from People Who Inject Drugs in Indonesia, Ukraine, and Vietnam: HPTN 074.

BACKGROUND: HIV Prevention Trials Network (HPTN) 074 evaluated human immunodeficiency virus (HIV) prevention interventions for people who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. Study interventions included support for HIV infection and substance use treatment. The study enrolled index participants living with HIV and injection partners who were not living with HIV. Seven partners acquired HIV infection during the study (seroconverters). We analyzed the phylogenetic relatedness between HIV strains in the cohort and the multiplicity of infection in seroconverters. METHODS: Pol region consensus sequences were used for phylogenetic analysis. Data from next-generation sequencing (NGS, env region) were used to evaluate genetic linkage of HIV from the 7 seroconverters and the corresponding index participants (index-partner pairs), to analyze HIV from index participants in pol sequence clusters, and to analyze multiplicity of HIV infection. RESULTS: Phylogenetic analysis of pol sequences from 445 index participants and 7 seroconverters identified 18 sequence clusters (2 index-partner pairs, 1 partner-partner pair, and 15 index-only groups with 2-7 indexes/cluster). Analysis of NGS data confirmed linkage for the 2 index-partner pairs, the partner-partner pair, and 11 of the 15 index-index clusters. The remaining 5 seroconverters had infections that were not linked to the corresponding enrolled index participant. Three (42.9%) of the 7 seroconverters were infected with more than 1 HIV strain (3-8 strains per person). CONCLUSIONS: We identified complex patterns of HIV clustering and linkage among PWID in 3 communities. This should be considered when designing strategies for HIV prevention for PWID. CLINICAL TRIALS REGISTRATION: NCT02935296.

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viraemia during Universal Test and Treat scale-up in Uganda: a population-based study.

INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. METHODS: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). CONCLUSIONS: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

The intersection between migration, HIV, and family planning in Uganda: a cross-sectional population-based study.

Background: Low use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use. Methods: We analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand. Results: There were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (±8) years, and 17.3% (n=591) were living with HIV. Overall, 43.9% (n=1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR]=1.14; 95% confidence interval [95%CI]: 1.02-1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR=0.80; 95%CI=0.70-0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant. Conclusions: Unsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.

Implications of rapid population growth on survey design and HIV estimates in the Rakai Community Cohort Study (RCCS), Uganda.

OBJECTIVE: Since rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia. DESIGN, SETTING AND PARTICIPANTS: Data were obtained from the Rakai Community Cohort Study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. The study includes adults aged 15-49 years who were censused from 2019 to 2020. MEASURES: We fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates. RESULTS: Of the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)-somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15-24 years was 4.9% (95% CI: 3.6% to 6.1%)-significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25-49 years was 15.0% (95% CI: 13.3% to 16.4%)-significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%). CONCLUSIONS: Exclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall, HIV seroprevalence estimates were not significantly affected.

Self-collected samples as an additional option for STI testing in low-resource settings: a qualitative study of acceptability among adults in Rakai, Uganda.

INTRODUCTION: Self-collected samples (SCS) for sexually transmitted infection (STI) testing have been shown to be feasible and acceptable in high-resource settings. However, few studies have assessed the acceptability of SCS for STI testing in a general population in low-resource settings. This study explored the acceptability of SCS among adults in south-central Uganda. METHODS: Nested within the Rakai Community Cohort Study, we conducted semistructured interviews with 36 adults who SCS for STI testing. We analysed the data using an adapted version of the Framework Method. RESULTS: Overall, SCS was acceptable to both male and female participants, regardless of whether they reported recent STI symptoms. Perceived advantages of SCS over provider-collection included increased privacy and confidentiality, gentleness and efficiency. Disadvantages included the lack of provider involvement, fear of self-harm and the perception that SCS was unhygienic. Most participants preferred provider-collected samples to SCS. Nevertheless, almost all said they would recommend SCS and would do it again in the future. CONCLUSION: SCS are acceptable among adults in this low-resource setting and could be offered as an additional option to expand STI diagnostic services.

Hypertension and Socioeconomic Status in South Central Uganda: A Population-Based Cohort Study.

Background: Limited studies exploring the impact of socioeconomic status (SES) on hypertension in Africa suggest a positive association between higher SES and hypertension. The economic development in sub-Saharan African countries has led to changes in SES and associated changes in lifestyle, diet, and physical activity, which may affect the relationship between hypertension and SES differently compared with higher income countries. This cross-sectional study from a large population-based cohort, the Rakai Community Cohort Study (RCCS), examines SES, hypertension prevalence, and associated risk factors in the rural Rakai Region in south-central Uganda. Methods: Adults aged 30-49 years residing in 41 RCCS fishing, trading, and agrarian communities, were surveyed with biometric data obtained between 2016 and 2018. The primary outcome was hypertension (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 80 mmHg). Modified Poisson regression assessed the adjusted prevalence ratios (PR) of hypertension associated with SES; body mass index (BMI) was explored as a potential mediator. Results: Among 9,654 adults, 20.8% had hypertension (males 21.2%; females 20.4 %). Participants with hypertension were older (39.0 ± 6.0 vs. 37.8 ± 5.0; p < 0.001). Higher SES was associated with overweight or obese BMI categories (p < 0.001). In the multivariable model, hypertension was associated with the highest SES category (aPR 1.23; confidence interval 1.09-1.38; p = 0.001), older age, male sex, alcohol use, and living in fishing communities and inversely associated with smoking and positive HIV serostatus. When BMI was included in the model, there was no association between SES and hypertension (aPR 1.02; CI 0.90-1.15, p = 0.76). Conclusion: Hypertension is common in rural Uganda among individuals with higher SES and appears to be mediated by BMI. Targeted interventions could focus on lifestyle modification among highest-risk groups to optimize public health impact. Key Messages: What is already known about this subject? Hypertension is an important modifiable risk factor for cardiovascular disease.There are few large epidemiological studies that investigate the relationship between hypertension and socioeconomic status in low-income countries. What are the new findings? Hypertension is common among adults in rural South-Central Uganda, particularly among those with higher socioeconomic status.BMI is a mediator of the relationship between hypertension and socioeconomic status. How might it impact on clinical practice in the foreseeable future? These findings suggest that public health interventions and community efforts to prevent chronic cardiovascular disease and hypertension should focus on lifestyle modification by elucidating obesity risk perception and health risk awareness, particularly among those of higher socioeconomic status.

Overweight and obesity in south central Uganda: A population-based study.

Obesity is a rapidly growing global health challenge, but there are few population-level studies from non-urban settings in sub-Saharan Africa. We evaluated the prevalence of overweight (body mass index (BMI)>25 kg/m2), obesity (BMI>30 kg/m2), and associated factors using data from May 2018 to November 2020 from the Rakai Community Cohort Study, a population-based cohort of residents aged 15 to 49 living in forty-one fishing, trading, and agrarian communities in South Central Uganda. Modified Poisson regression was used to estimate adjusted prevalence risk ratios (PRR) and 95% confidence intervals (CI) in 18,079 participants. The overall mean BMI was 22.9 kg/m2. Mean BMI was 21.5 kg/m2 and 24.1 kg/m2 for males and females, respectively. The prevalence of overweight and obesity were 22.8% and 6.2%, respectively. Females had a higher probability of overweight/obesity (PRR: 4.11, CI: 2.98-5.68) than males. For female participants, increasing age, higher socioeconomic status, residing in a trading or fishing community (PRR: 1.25, CI 1.16-1.35 and PRR: 1.17, CI 1.10-1.25, respectively), being currently or previously married (PRR: 1.22, CI 1.07-1.40 and PRR: 1.16, CI 1.01-1.34, respectively), working in a bar/restaurant (PRR: 1.29, CI 1.17-1.45), trading/shopkeeping (PRR: 1.38, CI 1.29-1.48), and reporting alcohol use in the last year (PRR: 1.21, CI 1.10-1.33) were risk factors for overweight/obese. For male participants, increasing age, higher socioeconomic status, being currently married (PRR: 1.94, CI 1.50-2.50), residing in a fishing community (PRR: 1.68, CI 1.40-2.02), working in a bar/restaurant (PRR: 2.20, CI 1.10-4.40), trading/shopkeeping (PRR: 1.75, CI 1.45-2.11), or fishing (PRR: 1.32, CI 1.03-1.69) increased the probability of overweight/obesity. Non-Muslim participants, male smokers, and HIV-positive females had a lower probability of overweight/obese. The prevalence of overweight/obesity in non-urban Ugandans is substantial. Targeted interventions to high-risk subgroups in this population are needed.

HIV-1 diversity among young women in rural South Africa: HPTN 068.

BACKGROUND: South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa. METHODS: Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13-20 years (Mpumalanga province, 2011-2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software. RESULTS: The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6-7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2-6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931-1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3-2.81x10-3) per site per year. CONCLUSIONS: Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial.