Acceptability and feasibility of mobile phone-based ecological momentary assessment and intervention in Uganda: A pilot randomized controlled trial.

Valid, reliable behavioral data and contextually meaningful interventions are necessary for improved health outcomes. Ecological Momentary Assessment and Intervention (EMAI), which collects data as behaviors occur to deliver real-time interventions, may be more accurate and reliable than retrospective methods. The rapid expansion of mobile technologies in low-and-middle-income countries allows for unprecedented remote data collection and intervention opportunities. However, no previous studies have trialed EMAI in sub-Saharan Africa. We assessed EMAI acceptability and feasibility, including participant retention and response rate, in a prospective, parallel group, randomized pilot trial in Rakai, Uganda comparing behavioral outcomes among adults submitting ecological momentary assessments (EMA) versus EMAI. After training, participants submitted EMA data on five nutrition and health risk behaviors over a 90-day period using a smartphone-based application utilizing prompt-based, participant-initiated, and geospatial coordinate data collection, with study coordinator support and incentives for >50% completion. Included behaviors and associated EMAI-arm intervention messages were selected to pilot a range of EMAI applications. Acceptability was measured on questionnaires. We estimated the association between high response rate and participant characteristics and conducted thematic analysis characterizing participant experiences. Study completion was 48/50 participants. Median prompt response rate was 66.5% (IQR: 60.0%-78.6%). Prior smartphone app use at baseline (aPR 3.76, 95%CI: 1.16-12.17, p = 0.03) and being in the intervention arm (aPR 2.55, 95% CI: 1.01-6.44, p = 0.05) were significantly associated with the top response rate quartile (response to >78.6% of prompts). All participants submitted self-initiated reports, covering all behaviors of interest, including potentially sensitive behaviors. Inconsistent phone charging was the most reported feasibility challenge. In this pilot, EMAI was acceptable and feasible. Response rates were good; additional strategies to improve compliance should be investigated. EMAI using mobile technologies may support improved behavioral data collection and intervention approaches in low and middle-income settings. This approach should be tested in larger studies.

Periodic synchronisation of dengue epidemics in Thailand over the last 5 decades driven by temperature and immunity.

The spatial distribution of dengue and its vectors (spp. Aedes) may be the widest it has ever been, and projections suggest that climate change may allow the expansion to continue. However, less work has been done to understand how climate variability and change affects dengue in regions where the pathogen is already endemic. In these areas, the waxing and waning of immunity has a large impact on temporal dynamics of cases of dengue haemorrhagic fever. Here, we use 51 years of data across 72 provinces and characterise spatiotemporal patterns of dengue in Thailand, where dengue has caused almost 1.5 million cases over the last 30 years, and examine the roles played by temperature and dynamics of immunity in giving rise to those patterns. We find that timescales of multiannual oscillations in dengue vary in space and time and uncover an interesting spatial phenomenon: Thailand has experienced multiple, periodic synchronisation events. We show that although patterns in synchrony of dengue are similar to those observed in temperature, the relationship between the two is most consistent during synchronous periods, while during asynchronous periods, temperature plays a less prominent role. With simulations from temperature-driven models, we explore how dynamics of immunity interact with temperature to produce the observed patterns in synchrony. The simulations produced patterns in synchrony that were similar to observations, supporting an important role of immunity. We demonstrate that multiannual oscillations produced by immunity can lead to asynchronous dynamics and that synchrony in temperature can then synchronise these dengue dynamics. At higher mean temperatures, immune dynamics can be more predominant, and dengue dynamics more insensitive to multiannual fluctuations in temperature, suggesting that with rising mean temperatures, dengue dynamics may become increasingly asynchronous. These findings can help underpin predictions of disease patterns as global temperatures rise.

Prevalence of Untreated HIV and Associated Risk Behaviors Among the Sexual Partners of Recent Migrants and Long-term Residents in Rakai, Uganda.

BACKGROUND: Migrants in sub-Saharan Africa are at increased risk of HIV acquisition after migration, but little is known about their sexual partners at place of destination. SETTING: Rakai Community Cohort Study (RCCS) in Uganda. METHODS: From 1999 to 2016, persons aged 15-49 years were surveyed in the RCCS and reported on their 4 most recent sexual partners in the last year. We compared the characteristics of sexual partners reported by migrants moving into RCCS communities in the last 2 years (ie, in-migrants) with those of long-term residents with no recent migration history. Among a subset of participants in cohabitating epidemiologically linked couples of known HIV serostatus, we also assessed prevalence of having ≥1 untreated HIV-positive partner among in-migrants and long-term residents. RESULTS: One hundred sixteen thousand seven hundred forty-four sexual partners were reported by 29,423 participants. The sexual partnerships of in-migrants were significantly less likely to be marital, more likely to span community boundaries, and shorter in duration than those of long-term residents. In-migrants also reported more sexual partners and were less likely to know their partner's HIV status or to have told their partner their HIV status. Among 7558 epidemiologically linked couples, HIV-negative in-migrants were more likely to partner with untreated HIV-positive persons compared with HIV-negative long-term residents (women: 6.3% vs. 4.1%; prevalence risk ratio = 1.77, 95% confidence interval: 1.49 to 2.11; men: 6.9% vs. 3.9%; prevalence risk ratio = 1.72, 95% confidence interval: 1.38-2.14). CONCLUSION: There is a higher frequency of risky sexual behaviors among the partnerships of in-migrants compared with those of long-term residents. Among cohabitating couples, in-migrants are more likely to partner with untreated HIV-positive individuals.

Mobile Ecological Momentary Assessment and Intervention and Health Behavior Change Among Adults in Rakai, Uganda: Pilot Randomized Controlled Trial.

BACKGROUND: An extraordinary increase in mobile phone ownership has revolutionized the opportunities to use mobile health approaches in lower- and middle-income countries (LMICs). Ecological momentary assessment and intervention (EMAI) uses mobile technology to gather data and deliver timely, personalized behavior change interventions in an individual's natural setting. To our knowledge, there have been no previous trials of EMAI in sub-Saharan Africa. OBJECTIVE: To advance the evidence base for mobile health (mHealth) interventions in LMICs, we conduct a pilot randomized trial to assess the feasibility of EMAI and establish estimates of the potential effect of EMAI on a range of health-related behaviors in Rakai, Uganda. METHODS: This prospective, parallel-group, randomized pilot trial compared health behaviors between adult participants submitting ecological momentary assessment (EMA) data and receiving behaviorally responsive interventional health messaging (EMAI) with those submitting EMA data alone. Using a fully automated mobile phone app, participants submitted daily reports on 5 different health behaviors (fruit consumption, vegetable consumption, alcohol intake, cigarette smoking, and condomless sex with a non-long-term partner) during a 30-day period before randomization (P1). Participants were then block randomized to the control arm, continuing EMA reporting through exit, or the intervention arm, EMA reporting and behavioral health messaging receipt. Participants exited after 90 days of follow-up, divided into study periods 2 (P2: randomization + 29 days) and 3 (P3: 30 days postrandomization to exit). We used descriptive statistics to assess the feasibility of EMAI through the completeness of data and differences in reported behaviors between periods and study arms. RESULTS: The study included 48 participants (24 per arm; 23/48, 48% women; median age 31 years). EMA data collection was feasible, with 85.5% (3777/4418) of the combined days reporting behavioral data. There was a decrease in the mean proportion of days when alcohol was consumed in both arms over time (control: P1, 9.6% of days to P2, 4.3% of days; intervention: P1, 7.2% of days to P3, 2.4% of days). Decreases in sex with a non-long-term partner without a condom were also reported in both arms (P1 to P3 control: 1.9% of days to 1% of days; intervention: 6.6% of days to 1.3% of days). An increase in vegetable consumption was found in the intervention (vegetable: 65.6% of days to 76.6% of days) but not in the control arm. Between arms, there was a significant difference in the change in reported vegetable consumption between P1 and P3 (control: 8% decrease in the mean proportion of days vegetables consumed; intervention: 11.1% increase; P=.01). CONCLUSIONS: Preliminary estimates suggest that EMAI may be a promising strategy for promoting behavior change across a range of behaviors. Larger trials examining the effectiveness of EMAI in LMICs are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04375423; https://www.clinicaltrials.gov/ct2/show/NCT04375423.

HIV serologically indeterminate individuals: Future HIV status and risk factors.

BACKGROUND: Indeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and its sociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda. METHODS: 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15-49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results. RESULTS: The prevalence of HIV serologically indeterminate results was 4.9%. Indeterminate results were less likely among women than men (adjPR 0.76, 95% CI 0.71,0.81), in unmarried participants than married participants (adjPR 0.92, 95% CI 0.85,99), and in individuals with primary (adjPR 0.90, 95% CI 0.80,1.02), secondary (adjPR 0.83, 95% CI 0.73,0.96) and post-secondary (adjPR 0.75, 95% CI 0.60,0.94) education, relative to no education. The proportions of persons with indeterminate results progressing to HIV positive, negative or indeterminate results in subsequent visits was 5%, 71% and 24%, respectively. CONCLUSION: HIV serologically indeterminate results were associated with gender and marital status. HIV surveillance programs should develop a protocol for reporting individuals with mixed or persistently indeterminate HIV results on multiple follow-up visits. Most indeterminate results became HIV-negative over time, but follow-up is still needed to detect positive serologies.

Sociodemographic and behavioral characteristics associated with blood donation in the United States: a population-based study.

BACKGROUND: Contemporary population-based data on characteristics associated with blood donation in the United States (U.S.) are limited. STUDY DESIGN AND METHODS: A cross-sectional analysis was performed among 28,739 persons aged 18 years and older who participated in the 2016 National Health Interview Survey, a household survey of the noninstitutionalized U.S. civilian population. Analyses were weighted and accounted for the complex survey design. Adjusted prevalence ratios (aPR) were estimated by multivariable log-binomial regression. RESULTS: The percentage of individuals reporting a past-year history of blood donation was 5.7% (95% confidence interval [CI], 5.3%-6.1%) and was highest in the youngest age group (18-24 years, 8.4%). A past-year history of blood donation was more common in males compared to females (6.3% vs. 5.1%; aPR, 1.12 [95% CI, 0.99-1.27]) and those born in the U.S. compared to individuals born outside the U.S. (6.4% vs. 2.4%; aPR, 1.92 [95% CI, 1.49-2.47]). The percentage of individuals with a past-year history of blood donation was significantly lower in blacks (3.9%; aPR, 0.60 [95% CI, 0.47-0.75]) and Hispanics (3.0%; aPR, 0.63 [95% CI, 0.48-0.83]) in comparison to whites (6.9%). Being a college graduate, being employed, being physically active, and never being a cigarette smoker were factors positively associated with blood donation. The percentage of individuals with a past-year history of blood donation varied by geographic census region, with prevalence being higher in the Midwest (7.3%) and South (6.0%) compared to the Northeast (4.7%) and West (4.4%). CONCLUSION: Continued differences in the blood donor population with reference to the U.S. population underscore the need to understand barriers or deterrents to blood donation. Evidence-based donor recruitment and related policies remain imperative to ensure that there is a sustainable blood supply.

One-unit compared to two-unit platelet transfusions for adult oncology outpatients.

BACKGROUND AND OBJECTIVES: Platelet dosing has been studied in adult oncology inpatients, but there is almost no published evidence to guide platelet dosing for adult outpatients. We evaluated transfusion indices after 1 unit and 2 unit apheresis platelet transfusions at our hospital to determine whether a benefit to 2-unit transfusions could be detected. MATERIALS AND METHODS: A retrospective chart review was conducted of all adult oncology patients who received an outpatient platelet transfusion over a 16-month period (July 2016-November 2017). Pre- and post-transfusion platelet count, and chronology of subsequent platelet transfusions were compared. RESULTS: A total of 8467 platelet transfusions were administered to 602 patients during the study period. 59·8% of patients (n = 360) were transfused interchangeably with one or two platelets throughout the study period. The primary study population were comprised of these patients. On average, a 2-unit platelet transfusions resulted in a higher immediate post-transfusion platelet count (43 vs. 37 x 103 /µl, P < 0·001) and a lower corrected count increment (9707 vs. 14 060, P < 0·001). Transfusion with 2 platelets did not increase the number of days between outpatient transfusions (median; 4 vs. 4, P = 0·959) or the platelet count at the time of next transfusion (11 vs. 11 x 103 /µl, P = 0·147). CONCLUSION: Among adult, oncology outpatients that were transfused interchangeably with one or two units of platelets, transfusion with two platelets did not offer a durable improvement in platelet count or impact the subsequent transfusion schedule.

PANGEA-HIV 2: Phylogenetics And Networks for Generalised Epidemics in Africa.

PURPOSE OF REVIEW: The HIV epidemic in sub-Saharan Africa is far from being under control and the ambitious UNAIDS targets are unlikely to be met by 2020 as declines in per-capita incidence being largely offset by demographic trends. There is an increasing number of proven and specific HIV prevention tools, but little consensus on how best to deploy them. RECENT FINDINGS: Traditionally, phylogenetics has been used in HIV research to reconstruct the history of the epidemic and date zoonotic infections, whereas more recent publications focus on HIV diversity and drug resistance. However, it is also the most powerful method of source attribution available for the study of HIV transmission. The PANGEA (Phylogenetics And Networks for Generalized Epidemics in Africa) consortium has generated over 18 000 NGS HIV sequences from five countries in sub-Saharan Africa. Using phylogenetic methods, we will identify characteristics of individuals or groups, which are most likely to be at risk of infection or at risk of infecting others. SUMMARY: Combining phylogenetics, phylodynamics and epidemiology will allow PANGEA to highlight where prevention efforts should be focussed to reduce the HIV epidemic most effectively. To maximise the public health benefit of the data, PANGEA offers accreditation to external researchers, allowing them to access the data and join the consortium. We also welcome submissions of other HIV sequences from sub-Saharan Africa to the database.

Association of blood donation with iron deficiency among adolescent and adult females in the United States: a nationally representative study.

BACKGROUND: Blood donation results in a loss of iron stores, which is particularly concerning for young female blood donors. This study examines the association of blood donation and iron deficiency among adolescent and adult females in the United States. STUDY DESIGN AND METHODS: A cross-sectional analysis was performed using data from the 1999-2010 National Health and Nutrition Examination Survey (NHANES). Females who reported their blood donation history in the preceding year and had serum ferritin (SF) measurements were included. Analyses were weighted and stratified by adolescents (16-19 years; n = 2419) and adults (20-49 years; n = 7228). Adjusted prevalence ratios (aPRs) were estimated by multivariable Poisson regression. Standard errors were estimated by Taylor series linearization. RESULTS: Geometric mean SF levels (ng/mL) were lower in blood donors compared to nondonors among adolescents (21.2 vs. 31.4; p < 0.001) and among adults (26.2 vs. 43.7; p < 0.001). The prevalence of absent iron stores (SF < 12 ng/mL) was higher in blood donors compared to nondonors among adolescents (22.6% vs. 12.2%; aPR = 2.03 [95% confidence interval (CI) = 1.45-2.85]) and among adults (18.3% vs. 9.8%; aPR = 2.06 [95% CI = 1.48-2.88]). Additionally, the prevalence of iron deficiency anemia (SF < 26 ng/mL and hemoglobin < 12.0 g/dL) was also higher in blood donors compared to nondonors among adolescents (9.5% vs. 6.1%; aPR = 2.10 [95% CI = 1.13-3.90]) and among adults (7.9% vs. 6.1%; aPR = 1.74 [95% CI = 1.06-2.85]). Similar results were observed in a sensitivity analysis restricted to adolescents aged 16 to 18 years. CONCLUSIONS: Blood donation is associated with iron deficiency among adolescent and adult females in the United States. These national data call for further development and implementation of blood donation practices aimed toward mitigating iron deficiency.

Brief Report: Age-Disparate Relationships and HIV Prevalence Among Never Married Women in Rakai, Uganda.

BACKGROUND: Age-disparate relationships are associated with increased HIV prevalence. We determined whether the frequency of age-disparate relationships in never married women changed over time and whether they are associated with HIV prevalence in Rakai, Uganda. METHODS: A total of 10,061 never married women, aged 15-49 years, in the Rakai Community Cohort Study provided information on the age of their male sexual partners from 1997 to 2013. Logistic regression was used to assess trends in age-disparate relationships (≥5 years) between never married women and their male partners. Log-binomial regression was used to estimate adjusted prevalence ratios (adjPR) of HIV prevalence associated with age-disparate relationships. RESULTS: Two thousand nine hundred ninety-nine women (30%) had a male partner ≥5 years older, which remained stable over time. The prevalence of HIV among women in age-disparate relationships was 14%, 10% for women in relationships with men 0-4 years older (adjPR 1.36, 95% confidence interval: 1.22 to 1.53) not controlling women's age; however, after age adjustment, the impact of age-disparate relationships on HIV prevalence was attenuated. Age-disparate relationships were associated with increased HIV prevalence among women aged 15-17 years (adjPR 1.83, 95% confidence interval: 1.10 to 3.17), but not in other age groups. CONCLUSIONS: The frequency of age-disparate relationships among never married women was unchanged over a 15-year period in Rakai, Uganda. Age-disparate relationships were associated with increased HIV prevalence among adolescents aged 15-17 years, but not older women.

Evolution of HIV-1 within untreated individuals and at the population scale in Uganda.

HIV-1 undergoes multiple rounds of error-prone replication between transmission events, resulting in diverse viral populations within and among individuals. In addition, the virus experiences different selective pressures at multiple levels: during the course of infection, at transmission, and among individuals. Disentangling how these evolutionary forces shape the evolution of the virus at the population scale is important for understanding pathogenesis, how drug- and immune-escape variants are likely to spread in populations, and the development of preventive vaccines. To address this, we deep-sequenced two regions of the HIV-1 genome (p24 and gp41) from 34 longitudinally-sampled untreated individuals from Rakai District in Uganda, infected with subtypes A, D, and inter-subtype recombinants. This dataset substantially increases the availability of HIV-1 sequence data that spans multiple years of untreated infection, in particular for different geographical regions and viral subtypes. In line with previous studies, we estimated an approximately five-fold faster rate of evolution at the within-host compared to the population scale for both synonymous and nonsynonymous substitutions, and for all subtypes. We determined the extent to which this mismatch in evolutionary rates can be explained by the evolution of the virus towards population-level consensus, or the transmission of viruses similar to those that establish infection within individuals. Our findings indicate that both processes are likely to be important.

Migration and risk of HIV acquisition in Rakai, Uganda: a population-based cohort study.

BACKGROUND: In sub-Saharan Africa, migrants typically have higher HIV prevalence than non-migrants; however, whether HIV acquisition typically precedes or follows migration is unknown. We aimed to investigate the risk of HIV after migration in Rakai District, Uganda. METHODS: In a prospective population-based cohort of HIV-negative participants aged 15-49 years in Rakai, Uganda, between April 6, 1999, and Jan 30, 2015, we assessed the association between migration and HIV acquisition. Individuals were classified as recent in-migrants (≤2 years in community), non-recent in-migrants (>2 years in community), or permanent residents with no migration history. The primary outcome was incident HIV infection. We used Poisson regression to estimate incidence rate ratios (IRRs) of HIV associated with residence status with adjustment for demographics, sexual behaviours, and time. Data were also stratified and analysed within three periods (1999-2004, 2005-11, and 2011-15) in relation to the introduction of combination HIV prevention (CHP; pre-CHP, early CHP, and late CHP). FINDINGS: Among 26 995 HIV-negative people who participated in the Rakai Community Cohort Study survey, 15 187 (56%) contributed one or more follow-up visits (89 292 person-years of follow-up) and were included in our final analysis. 4451 (29%) were ever in-migrants and 10 736 (71%) were permanent residents. 841 incident HIV events occurred, including 243 (29%) among in-migrants. HIV incidence per 100 person-years was significantly increased among recent in-migrants compared with permanent residents, for both women (1·92, 95% CI 1·52-2·43 vs 0·93, 0·84-1·04; IRR adjusted for demographics 1·75, 95% CI 1·33-2·33) and men (1·52, 0·99-2·33 vs 0·84, 0·74-0·94; 1·74, 1·12-2·71), but not among non-recent in-migrants (IRR adjusted for demographics 0·94, 95% CI 0·74-1·19 for women and 1·28, 0·94-1·74 for men). Between the pre-CHP and late-CHP periods, HIV incidence declined among permanent resident men (p<0·0001) and women (p=0·002) and non-recent in-migrant men (p=0·031), but was unchanged among non-recent in-migrant women (p=0·13) and recent in-migrants (men p=0·76; women p=0·84) INTERPRETATION: The first 2 years after migration are associated with increased risk of HIV acquisition. Prevention programmes focused on migrants are needed to reduce HIV incidence in sub-Saharan Africa. FUNDING: National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Development, the National Institute for Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health; the Centers for Disease Control and Prevention; the Bill & Melinda Gates Foundation; and the Johns Hopkins University Center for AIDS Research.

HIV viral suppression and geospatial patterns of HIV antiretroviral therapy treatment facility use in Rakai, Uganda.

OBJECTIVE: To assess geospatial patterns of HIV antiretroviral therapy (ART) treatment facility use and whether they were impacted by viral load suppression. METHODS: We extracted data on the location and type of care services utilized by HIV-positive persons accessing ART between February 2015 and September 2016 from the Rakai Community Cohort Study in Uganda. The distance from Rakai Community Cohort Study households to facilities offering ART was calculated using the open street map road network. Modified Poisson regression was used to identify predictors of distance traveled and, for those traveling beyond their nearest facility, the probability of accessing services from a tertiary care facility. RESULTS: In total, 1554 HIV-positive participants were identified, of whom 68% had initiated ART. The median distance from households to the nearest ART facility was 3.10 km (interquartile range, 1.65-5.05), but the median distance traveled was 5.26 km (interquartile range, 3.00-10.03, P < 0.001) and 57% of individuals travelled further than their nearest facility for ART. Those with higher education and wealth were more likely to travel further. In total, 93% of persons on ART were virally suppressed, and there was no difference in the distance traveled to an ART facility between those with suppressed and unsuppressed viral loads (5.26 vs. 5.27 km, P = 0.650). CONCLUSION: Distance traveled to HIV clinics was increased with higher socioeconomic status, suggesting that wealthier individuals exercise greater choice. However, distance traveled did not vary by those who were or were not virally suppressed.

The validity of self-reported antiretroviral use in persons living with HIV: a population-based study.

OBJECTIVE: To assess the validity of self-reported antiretroviral therapy use (ART) using population-based cohort data. METHODS: Self-reported ART use and nonuse was compared with a validated laboratory assay in 557 HIV-positive participants in the Rakai Community Cohort Study surveyed between September and December 2011 in Rakai, Uganda. The study population included participants from seven communities, including one fishing community with high HIV prevalence (∼41%). ART use was assayed using liquid chromatography-tandem mass spectrometry, which detects 20 antiretroviral drugs. HIV viral load measurements were also obtained. Individuals with at least two antiretroviral drugs detected were considered to be using ART. RESULTS: One hundred and fifty-three (27%) participants self-reported ART use of whom 148 (97%) had at least two antiretroviral drugs detected. There were at least two antiretroviral drugs detected in 11% (n = 44/404) of individuals with no self-reported ART use. Overall, the specificity of self-reported ART use was 99% (95% CI 97-100%) and the sensitivity was 77% (70-83%). Positive and negative predictive values were 97% (95% CI 93-99%) and 89% (95% CI 86-92%), respectively. Nondisclosure of ART use was significantly more common in younger persons (<30 years) and among those in trading occupations. CONCLUSION: Self-reported ART use has high specificity and moderate sensitivity providing reasonable, but conservative estimates of population-based ART use. There is more under-reporting of ART use among younger persons and traders suggesting a need for more research on barriers to self-reporting of ART use in these sub-groups.

Human immunodeficiency virus care cascade among sub-populations in Rakai, Uganda: an observational study.

INTRODUCTION: To assess progress towards the UNAIDS 90-90-90 initiative targets, we examined the HIV care cascade in the population-based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub-groups. METHODS: Self-reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ2 test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART). RESULTS: From September 2013 through December 2015, 3,666 HIV-positive participants were identified in the RCCS. As of December 2015, 98% had received HIV Counseling and Testing (HCT), 74% were enrolled in HIV care, and 63% had initiated ART of whom 92% were virally suppressed after 12 months on ART. Engagement in care was lower among men than women (enrolment in care: adjPRR 0.84, 95% CI 0.77-0.91; ART initiation: adjPRR 0.75, 95% CI 0.69-0.82), persons aged 15-24 compared to those aged 30-39 (enrolment: adjPRR 0.72, 95% CI 0.63-0.82; ART: adjPRR 0.69, 95%CI 0.60-0.80), unmarried persons (enrolment: adjPRR 0.84, 95% CI 0.71-0.99; ART adjPRR 0.80, 95% CI 0.66-0.95), and new in-migrants (enrolment: adjPRR 0.75, 95% CI 0.67-0.83; ART: adjPRR 0.76, 95% CI 0.67-0.85). This cohort achieved 98-65-92 towards the UNAIDS "90-90-90" targets with an estimated 58% of the entire HIV-positive RCCS population virally suppressed. CONCLUSIONS: This cohort achieved over 90% in both HCT and viral suppression among ART users, but only 65% in initiating ART, likely due to both an ART eligibility criterion of <500 CD4 cells/mL and suboptimal entry into care among men, younger individuals, and in-migrants. Interventions are needed to promote enrolment in HIV care, particular for hard-to-reach sub-populations.

Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation.

OBJECTIVE: To assess the association between cytomegalovirus (CMV) IgG antibody levels, HIV disease progression, and immune activation markers. DESIGN: A prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda. METHODS: The primary endpoints were progression to a CD4 T-cell count less than 250 cells/µl, nontraumatic death, or initiation of antiretroviral therapy (ART). CD4 T-cell counts, HIV viral load, C-reactive protein (CRP), and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibodies were measured at baseline among all women and annually among a subset of women who initiated ART. RESULTS: There were 300 HIV/CMV-coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared with the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4 T-cell count, and HIV viral load at baseline [adjusted hazard ratio = 1.59; (95% CI = 1.05-2.39); P = 0.027]. Among pre-ART visits (n = 1200), women in the highest baseline CMV IgG tertile had increasing annual rates of soluble CD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared with pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with soluble CD14 and CRP during suppressive ART (n = 88 person-visits). CONCLUSION: The magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.

Trends and Determinants of Human Papillomavirus Concordance Among Human Immunodeficiency Virus-Positive and -Negative Heterosexual Couples in Rakai, Uganda.

Background: Limited data are available on human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-negative or HIV-positive couples followed longitudinally. Methods: Genital HPV was assessed in 725 concordant HIV-negative couples and 209 HIV-positive couples enrolled in a male circumcision trial in Rakai, Uganda, using the Roche Linear Array assay, which detects 37 HPV genotypes. Human papillomavirus prevalence and determinants of genotype-specific concordance were assessed at annual visits. Cumulative detection of HPV genotypes over 2 years was also assessed. Results: At enrollment, HPV infection was detected in 54% of HIV-negative women, 56% of HIV-negative men, and 93% of HIV-positive men and women. For HIV-negative couples, genotypic concordance was 30% at baseline (n = 219/725) and declined significantly with age (adjusted prevelance risk ratio [adjPRR] = 0.53; 95% confidence interval [CI] = 0.28-0.93 comparing women aged >40 years to those aged 15-19 years) and male circumcision (adjPRR = 0.60; 95% CI = 0.47-0.77) and increased among couples with recent intercourse (adjPRR = 1.26; 95% CI = 1.04-1.53). These associations were not seen in HIV-positive couples. Among couples with HPV results at all visits, ≥1 of the same genotypes were detected in both partners in 60% of HIV-negative couples and 96% of HIV-positive couples over 2 years. Conclusion: Human papillomavirus genotype-specific concordance is more common in HIV-positive couples, and irrespective of HIV status, the majority of couples exhibit HPV concordance over 2 years.

Identifying Transmission Clusters with Cluster Picker and HIV-TRACE.

We compared the behavior of two approaches (Cluster Picker and HIV-TRACE) at varying genetic distances to identify transmission clusters. We used three HIV gp41 sequence datasets originating from the Rakai Community Cohort Study: (1) next-generation sequence (NGS) data from nine linked couples; (2) NGS data from longitudinal sampling of 14 individuals; and (3) Sanger consensus sequences from a cross-sectional dataset (n = 1,022) containing 91 epidemiologically linked heterosexual couples. We calculated the optimal genetic distance threshold to separate linked versus unlinked NGS datasets using a receiver operating curve analysis. We evaluated the number, size, and composition of clusters detected by Cluster Picker and HIV-TRACE at six genetic distance thresholds (1%-5.3%) on all three datasets. We further tested the effect of using all NGS, versus only a single variant for each patient/time point, for datasets (1) and (2). The optimal gp41 genetic distance threshold to distinguish linked and unlinked couples and individuals was 5.3% and 4%, respectively. HIV-TRACE tended to detect larger and fewer clusters, whereas Cluster Picker detected more clusters containing only two sequences. For NGS datasets (1) and (2), HIV-TRACE and Cluster Picker detected all linked pairs at 3% and 4% genetic distances, respectively. However, at 5.3% genetic distance, 20% of couples in dataset (3) did not cluster using either program, and for >1/3 of couples cluster assignment were discordant. We suggest caution in choosing thresholds for clustering analyses in a generalized epidemic.

Heterogeneity of the HIV epidemic in agrarian, trading, and fishing communities in Rakai, Uganda: an observational epidemiological study.

BACKGROUND: Understanding the extent to which HIV burden differs across communities and the drivers of local disparities is crucial for an effective and targeted HIV response. We assessed community-level variations in HIV prevalence, risk factors, and treatment and prevention service uptake in Rakai, Uganda. METHODS: The Rakai Community Cohort Study (RCCS) is an open, population-based cohort of people aged 15-49 years in 40 communities. Participants are HIV tested and interviewed to obtain sociodemographic, behavioural, and health information. RCCS data from Aug 10, 2011, to May 30, 2013, were used to classify communities as agrarian (n=27), trading (n=9), or lakeside fishing sites (n=4). We mapped HIV prevalence with Bayesian methods, and characterised variability across and within community classifications. We also assessed differences in HIV risk factors and uptake of antiretroviral therapy and male circumcision between community types. FINDINGS: 17 119 individuals were included, 9215 (54%) of whom were female. 9931 participants resided in agrarian, 3318 in trading, and 3870 in fishing communities. Median HIV prevalence was higher in fishing communities (42%, range 38-43) than in trading (17%, 11-21) and agrarian communities (14%, 9-26). Antiretroviral therapy use was significantly lower in both men and women in fishing communities than in trading (age-adjusted prevalence risk ratio in men 0·64, 95% CI 0·44-0·97; women 0·53, 0·42-0·66) and agrarian communities (men 0·55, 0·42-0·72; women 0·65, 0·54-0·79), as was circumcision coverage among men (vs trading 0·48, 0·42-0·55; vs agrarian 0·64, 0·56-0·72). Self-reported risk behaviours were significantly higher in men than in women and in fishing communities than in other community types. INTERPRETATION: Substantial heterogeneity in HIV prevalence, risk factors, and service uptake in Rakai, Uganda, emphasises the need for local surveillance and the design of targeted HIV responses. High HIV burden, risk behaviours, and low use of combination HIV prevention in fishing communities make these populations a priority for intervention. FUNDING: National Institute of Mental Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Development, and the National Institute for Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health; the Bill & Melinda Gates Foundation; and the Johns Hopkins University Center for AIDS Research.

HIV-1 Sequence Data Coverage in Central East Africa from 1959 to 2013.

Central and Eastern African HIV sequence data have been most critical in understanding the establishment and evolution of the global HIV pandemic. Here we report on the extent of publicly available HIV genetic sequence data in the Los Alamos National Laboratory Sequence Database sampled from 1959 to 2013 from six African countries: Uganda, Kenya, Tanzania, Burundi, the Democratic Republic of Congo, and Rwanda. We have summarized these data, including HIV subtypes, the years sampled, and the genomic regions sequenced. We also provide curated alignments for this important geographic area in five HIV genomic regions with substantial coverage.