Motivational interviewing experiences from a community health worker-led HIV prevention and care intervention in rural Uganda: a qualitative study.

Motivational Interviewing (MI) and Community Health Workers (CHWs) are increasingly utilized in global settings to improve HIV outcomes, yet research exploring implementation strategies using MI and CHWs is lacking. We examined the experiences of CHWs and their clients in a counseling intervention which used MI-informed counseling to increase engagement in HIV prevention and treatment. This study was nested within the mLAKE cluster-randomized trial in a high HIV prevalence fishing community in rural Rakai District, Uganda. We conducted in-depth interviews with purposively-sampled CHWs (n = 8) and clients (n = 51). Transcripts were analyzed thematically to characterize CHWs' implementation of the intervention. Main themes identified included use of specific MI strategies (including evocation, guidance towards positive behavior change, active listening, and open-ended questions), and MI spirit (including collaboration, power-sharing, trust, and non-judgmental relationship building). Through these specific MI mechanisms, CHWs supported client behavior change to facilitate engagement with HIV services. This study provides evidence from a low-resource setting that CHWs with no previous experience in MI can successfully implement MI-informed counseling that is well-received by clients. CHW-led MI-informed counseling appears to be a feasible and effective approach to increase uptake of HIV prevention and care services in low-resource, HIV endemic regions.

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.

Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda.

BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. RESULTS: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai, Uganda: A pragmatic, cluster-randomized trial.

BACKGROUND: Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services. METHODS AND FINDINGS: The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect. CONCLUSIONS: A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02556957.

Assessment, prevalence, and correlates of frailty among middle-aged adults with HIV in rural Uganda.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

Improvement in depressive symptoms after antiretroviral therapy initiation in people with HIV in Rakai, Uganda.

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aß-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences.

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1ß, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.

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.).

The Veterans Aging Cohort Study Index is not associated with HIV-associated neurocognitive disorders in Uganda.

The Veterans Aging Cohort Study (VACS) Index has been associated with HIV-associated neurocognitive disorder (HAND) in some populations but has not been studied in sub-Saharan Africa. We investigated whether the VACS Index is associated with HAND in a rural population in Rakai, Uganda. HIV-infected (HIV+) adults on antiretroviral therapy underwent a neurocognitive battery for determination of HAND stage using Frascati criteria. VACS component scores were recorded for all participants. Out of 156 study participants, HAND stages were 49% normal cognition, 15% asymptomatic neurocognitive impairment, 31% minor neurocognitive disorder, and 7% HIV-associated dementia. There was no significant association between VACS Index and any HAND stage. In this first study of the VACS Index in sub-Saharan Africa, we found no association between VACS Index score and HAND.

Risk and protective factors associated with BV chronicity among women in Rakai, Uganda.

OBJECTIVES: To assess risk and protective factors associated with bacterial vaginosis (BV) chronicity ascertained by Nugent score criteria. METHODS: A longitudinal cohort study included 255 sexually experienced, postmenarcheal women who provided weekly self-collected vaginal swabs for up to 2 years. Vaginal swabs were scored using Nugent criteria and classified as normal (≤3), intermediate (4-6) and Nugent-BV (≥7). Detailed behavioural/health information were assessed every 6 months. A per-woman longitudinal summary measure of BV chronicity was defined as the percentage of each woman's weekly vaginal assessments scored as Nugent-BV over a 6-month interval. Risk and protective factors associated with BV chronicity were assessed using multiple linear regression with generalised estimating equations. RESULTS: Average BV chronicity was 39% across all follow-up periods. After adjustment, factors associated with BV chronicity included baseline Nugent-BV (ß=35.3, 95% CI 28.6 to 42.0) compared with normal baseline Nugent scores and use of unprotected water for bathing (ie, rainwater, pond, lake/stream) (ß=12.0, 95% CI 3.4 to 20.5) compared with protected water sources (ie, well, tap, borehole). Women had fewer BV occurrences if they were currently pregnant (ß=-6.6, 95% CI -12.1 to 1.1), reported consistent condom use (ß=-7.7, 95% CI -14.2 to 1.3) or their partner was circumcised (ß=-5.8, 95% CI -11.3 to 0.3). CONCLUSIONS: Factors associated with higher and lower values of BV chronicity were multifactorial. Notably, higher values of BV chronicity were associated with potentially contaminated bathing water. Future studies should examine the role of waterborne microbial agents in the pathogenesis of BV.

Cell Phones, Sexual Behaviors and HIV Prevalence in Rakai, Uganda: A Cross Sectional Analysis of Longitudinal Data.

Cell phones have increased communication and connection across the globe and particularly in sub-Saharan Africa-with potential consequences for the HIV epidemic. We examined the association among ownership of cell phones, sexual behaviors (number of sexual partners, alcohol use before sex, inconsistent condom use), and HIV prevalence. Data were from four rounds (2010-2016) of the Rakai Community Cohort Study (N = 58,275). Sexual behaviors and HIV prevalence were compared between people who owned a cell phone to people who did not own a cell phone. We stratified analysis by younger (15-24 years) and older (25+ years) age groups and by gender. Using logistic regression and after adjusting for sociodemographic characteristics, we found cell phone ownership was independently associated with increased odds of having two or more sexual partners in the past 12 months across age and gender groups (young men AOR 1.67, 95% CI 1.47-1.90; young women AOR 1.28 95% CI 1.08-1.53; older men AOR 1.54 95% CI 1.41-1.69; older women AOR 1.44 95% CI 1.26-1.65). Interestingly, young men who owned cell phones had decreased odds of using condoms inconsistently (AOR 0.66, 95% CI 0.57-0.75). For young women, cell phone ownership was associated with increased odds of using alcohol before sex (AOR 1.38 95% CI 1.17-1.63) and increased odds of inconsistent condom use (AOR 1.40, 95% 1.17-1.67). After adjusting for sociodemographic characteristics, only young women who owned cell phones had increased odds of being HIV positive (AOR 1.27 95% CI 1.07-1.50). This association was not mediated by sexual behaviors (Adjusted for sociodemographic characteristics and sexual behaviors AOR 1.24, 95% CI 1.05-1.46). While cell phone ownership appears to be associated with increased HIV risk for young women, we also see a potential opportunity for future cell phone-based health interventions.

Antiretroviral treatment sharing among highly mobile Ugandan fisherfolk living with HIV: a qualitative study.

Antiretroviral treatment (ART) diversion from prescribed to non-prescribed users (i.e., sharing or selling) is an understudied dimension of HIV treatment adherence. We sought to explore ART diversion patterns in high-prevalence fishing communities on Lake Victoria, Uganda. We implemented a qualitative study in two fishing communities on Lake Victoria in south-central Uganda to identify facilitators of and pathways to ART diversion. We conducted 25 semi-structured interviews with HIV-positive fishermen (n = 25) and female sex workers (n = 10) covering personal and community experiences with ART selling/sharing, reasons for medication diversion, and potential solutions to reduce diversion. Data were analyzed using an adapted framework analysis approach. Participants reported frequent ART sharing within occupational networks, but no selling. Mobility was the principal driver of ART sharing and was associated with other barriers to treatment access including stigma, fear of negative health provider interactions, and transportation. ART sharing appears to emerge in response to short-term treatment interruptions in this setting. Future studies should explore characteristics and drivers of ART diversion in other high-burden settings and identify how these practices are correlated with key health outcomes like virologic failure and drug resistance.

Vitamin D is not associated with HIV-associated neurocognitive disorder in Rakai, Uganda.

We investigated whether vitamin D is associated with HIV-associated neurocognitive disorder (HAND). HIV-infected (HIV+) antiretroviral therapy (ART)-naïve adults in rural Uganda underwent a neurocognitive battery for determination of HAND stage at baseline and after 2 years. Baseline serum 25-hydroxyvitamin D (25OH-D) and serum and cerebrospinal fluids (CSF) vitamin D-binding protein (VDBP) were obtained. Of the 399 participants, 4% (n = 16) were vitamin D deficient (25OH-D < 20 ng/mL). There was no association between 25OH-D, serum or CSF VDBP, and HAND stage at baseline or follow-up. Future studies in a population with higher levels of vitamin D deficiency may be warranted.

Interleukin-6 is associated with mortality and neuropsychiatric outcomes in antiretroviral-naïve adults in Rakai, Uganda.

Serum interleukin-6 (IL-6) and D-dimer have been associated with multiple adverse outcomes in HIV-infected (HIV+) individuals, but their association with neuropsychiatric outcomes, including HIV-associated neurocognitive disorder (HAND) and depression, headaches, and peripheral neuropathy have not been investigated. Three hundred ninety-nine HIV+ antiretroviral therapy (ART)-naïve adults in Rakai, Uganda, were enrolled in a longitudinal cohort study and completed a neurological evaluation, neurocognitive assessment, and venous blood draw. Half of the participants had advanced immunosuppression (CD4 count < 200 cells/µL), and half had moderate immunosuppression (CD4 count 350-500 cells/µL). All-cause mortality was determined by verbal autopsy within 2 years. HAND was determined using Frascati criteria, and depression was defined by the Center for Epidemiologic Studies-Depression (CES-D) scale. Neuropathy was defined as the presence of > 1 neuropathy symptom and > 1 neuropathy sign. Headaches were identified by self-report. Serum D-dimer levels were determined using ELISA and IL-6 levels using singleplex assays. Participants were 53% male, mean age 35 + 8 years, and mean education 5 + 3 years. Participants with advanced immunosuppression had significantly higher levels of IL-6 (p < 0.001) and a trend toward higher D-dimer levels (p = 0.06). IL-6 was higher among participants with HAND (p = 0.01), with depression (p = 0.03) and among those who died within 2 years (p = 0.001) but not those with neuropathy or headaches. D-dimer did not vary significantly by any outcome. Systemic inflammation as measured by serum IL-6 is associated with an increased risk of advanced immunosuppression, all-cause mortality, HAND, and depression but not neuropathy or headaches among ART-naïve HIV+ adults in rural Uganda.

Headache prevalence and its functional impact among HIV-infected adults in rural Rakai District, Uganda.

Headache is common, but its prevalence and impact in sub-Saharan Africa and especially in HIV+ individuals is relatively unknown. We sought to determine the prevalence and functional impact of headache among HIV-infected (HIV+) adults in a cross-sectional observational cohort study in rural Rakai District, Uganda. Participants completed a sociodemographic survey, depression screen, functional status assessments, and answered the headache screening question, "Do you have headaches?" Participants responding affirmatively were assessed with the ID Migraine tool for diagnosis of migraine and Headache Impact Test-6 to determine functional impact of headache. Characteristics of participants with and without headaches and with and without functional impairment were compared using t tests for continuous variables, chi-square tests for categorical variables, and multivariate logistic regression. Of 333 participants, 51% were males, mean age was 37 (SD 9) years, 94% were on antiretroviral therapy (ART) and mean CD4 count was 403 (SD 198) cells/µL. Headache prevalence was 28%. Among those reporting headache, 19% met criteria for migraine, 55% reported functional impairment, and 37% reported substantial or severe impact of headache. In multivariate analyses, female sex (odds ratio (OR) 2.58) and depression (OR 2.49) were associated with increased odds and ART (OR 0.33) with decreased odds of headache. Participants with substantial/severe functional impact were more likely to meet criteria for depression (32% vs 9%). In conclusion, headache prevalence in HIV+ rural Ugandans was lower than global averages but still affected more than one quarter of participants and was associated with significant functional impairment.

Heterogeneity in neurocognitive change trajectories among people with HIV starting antiretroviral therapy in Rakai, Uganda.

Considerable heterogeneity exists in patterns of neurocognitive change in people with HIV (PWH). We examined heterogeneity in neurocognitive change trajectories from HIV diagnosis to 1-2 years post-antiretroviral therapy (ART). In an observational cohort study in Rakai, Uganda, 312 PWH completed a neuropsychological (NP) test battery at two-time points (ART-naïve, 1-2 years post-ART initiation). All NP outcomes were used in a latent profile analysis to identify subgroups of PWH with similar ART-related neurocognitive change profiles. In a subset, we examined subgroup differences pre-ART on cytokine and neurodegenerative biomarkers CSF levels. We identified four ART-related change subgroups: (1) decline-only (learning, memory, fluency, processing speed, and attention measures), (2) mixed (improvements in learning and memory but declines in attention and executive function measures), (3) no-change, or (4) improvement-only (learning, memory, and attention measures). ART-related NP outcomes that are most likely to change included learning, memory, and attention. Motor function measures were unchanged. Subgroups differed on eight of 34 pre-ART biomarker levels including interleukin (IL)-1ß, IL-6, IL-13, interferon-γ, macrophage inflammatory protein-1ß, matrix metalloproteinase (MMP)-3, MMP-10, and platelet-derived growth factor-AA. The improvement-only and mixed subgroups showed lower levels on these markers versus the no-change subgroup. These findings provide support for the need to disentangle heterogeneity in ART-related neurocognitive changes, to focus on higher-order cognitive processes (learning, memory, attention) as they were most malleable to change, and to better understand why motor function remained unchanged despite ART treatment. Group differences in pre-ART CSF levels provide preliminary evidence of biological plausibility of neurocognitive phenotyping.

Hepatitis E Virus Seroprevalence and Correlates of Anti-HEV IgG Antibodies in the Rakai District, Uganda.

A cross-sectional study was conducted of 500 human immunodeficiency virus (HIV)-infected adults frequency matched on age, sex, and community to 500 HIV-uninfected individuals in the Rakai District, Uganda to evaluate seroprevalence of anti-hepatitis E virus (HEV) IgG antibodies. HEV seroprevalence was 47%, and 1 HIV-infected individual was actively infected with a genotype 3 virus. Using modified Poisson regression, male sex (prevalence ratios [PR] = 1.247; 95% confidence interval [CI], 1.071-1.450) and chronic hepatitis B virus infection (PR = 1.377; 95% CI, 1.090-1.738) were associated with HEV seroprevalence. HIV infection status (PR = 0.973; 95% CI, 0.852-1.111) was not associated with HEV seroprevalence. These data suggest there is a large burden of prior exposure to HEV in rural Uganda.

Chemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1 Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda.

Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95%CI 1.04-6.40) and Monokine Induced by γ-interferon (MIG aOR 2.72, 95%CI 1.15-8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man's female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95%CI 0.44-0.87), and continued to decline for at least two years (PRR 0.29, 95%CI 0.16-0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision.

HIV Partner Notification Values and Preferences Among Sex Workers, Fishermen, and Mainland Community Members in Rakai, Uganda: A Qualitative Study.

HIV partner notification involves contacting sexual partners of people who test HIV positive and referring them to HIV testing, treatment, and prevention services. To understand values and preferences of key and general populations in Rakai, Uganda, we conducted 6 focus group discussions and 63 in-depth interviews in high prevalence fishing communities and low prevalence mainland communities. Participants included fishermen and sex workers in fishing communities, male and female mainland community members, and healthcare providers. Questions explored three approaches: passive referral, provider referral, and contract referral. Qualitative data were coded and analyzed using a team-based matrix approach. Participants agreed that passive referral was most suitable for primary partners. Provider referral was acceptable in fishing communities for notifying multiple, casual partners. Healthcare providers voiced concerns about limited time, resources, and training for provider-assisted approaches. Options for partner notification may help people overcome barriers to HIV serostatus disclosure and help reach key populations.

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.