Browsing by Author "Hunt, Peter W."
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Item Association of Gut Intestinal Integrity and Inflammation with Insulin Resistance in Adults Living with HIV in Uganda(AIDS Patient Care and STDs, 2019) Reid, Michael J.A.; Ma, Yifei; Golovaty, Iya; Okello, Samson; Sentongo, Ruth; Feng, Maggie; Tsai, Alexander C.; Kakuhikire, Bernard; Tracy, Russell; Hunt, Peter W.; Siedner, Mark; Tien, Phyllis C.We conducted a cross-sectional study of 148 HIV+ on HIV antiretroviral therapy and 149 HIV- adults in Mbarara, Uganda, to estimate the association between HIV infection and homeostasis model assessment of insulin resistance (HOMA-IR) using multivariable regression analysis. In addition, we evaluated whether intestinal fatty acid-binding protein (I-FABP), monocyte activation markers soluble (s)CD14 and sCD163, and proinflammatory cytokine interleukin 6 (IL-6) mediated this association. HOMA-IR was greater among HIV+ than HIV- adults [median (interquartile range): 1.3 (0.7–2.5) vs. 0.9 (0.5–2.4); p = 0.008]. In models adjusted for sociodemographic variables, diet, hypertension, and smoking history, HIV infection was associated with 37% [95% confidence intervals (95% CIs): 5–77] greater HOMA-IR compared with HIV- participants. The magnitude of association was greater when I-FABP was included as a covariate although the additive effect was modest (40% CI: 8–82). By contrast adding sCD14 to the model was associated with greater HOMA-IR (59%; 95% CI: 21–109) among HIV+ participants compared with HIV- participants. Among HIV+ participants, greater CD4 nadir was non-significantly associated with greater HOMA-IR (22%; 95% CI: -2 to 52). Each 5-unit increase in body mass index (BMI; 49% greater HOMA-IR; 95% CI: 18–87) and female sex (71%; 95% CI: 17–150) remained associated in adjusted models. In this study of mainly normal-weight Ugandan adults, HIV infection, female sex, and greater BMI were all associated with greater insulin resistance (IR). This association was strengthened modestly after adjustment for sCD14, suggesting possible distinct immune pathways to IR that are independent of HIV or related to inflammatory changes occurring on HIV treatment.Item Changes in Food Insecurity, Nutritional Status, and Physical Health Status After Antiretroviral Therapy Initiation in Rural Uganda(Journal of acquired immune deficiency syndromes, 2012) Weiser, Sheri D.; Gupta, Reshma; Tsai, Alexander C.; Frongillo, Edward A.; Grede, Nils; Kumbakumba, Elias; Kawuma, Annet; Hunt, Peter W.; Bangsberg, David R.; Martin, Jeffrey N.To investigate whether time on antiretroviral therapy (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status. The Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda. Participants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each 3-month period. Outcomes were food insecurity, nutritional status, and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and sociodemographic characteristics.Item Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection(Oxford University Press, 2021) Schnittman, Samuel R.; Byakwaga, Helen; Boum, Yap; Kabakyenga, Jerome; Matthews, Lynn T.; Burdo, Tricia H.; Huang, Yong; Tracy, Russell P.; Haberer, Jessica E.; Kembabazi, Annet; Kaida, Angela; Moisi, Daniela; Lederman, Michael M.; Bangsberg, David R.; Martin, Jeffrey N.; Hunt, Peter W.Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum period. Women with HIV initiating antiretroviral therapy (ART) in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (n = 54). Plasma kynurenine/tryptophan (KT) ratio, soluble CD14 (sCD14), sCD163, sCD27, interferon-inducible protein 10 (IP-10), D-dimer, interleukin-6, and intestinal fatty-acid binding protein levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and 1 year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. Results. The median pre-ART CD4 count was 134. D-dimer increased through the third trimester before returning to baseline postpartum, while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above prepregnancy baseline postpartum (mean + 30%; P < .001) and remained higher than baseline for ≥9 months (P ≤ .045 for all time points). Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for ≥9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood but may contribute to increased tuberculosis risk in this setting.Item Contraceptive use following unintended pregnancy among Ugandan women living with HIV(PLoS ONE, 2018) Jarolimova, Jana; Kabakyenga, Jerome; Bennett, Kara; Muyindike, Winnie; Kembabazi, Annet; Martin, Jeffrey N.; Hunt, Peter W.; Boum, Yap; Haberer, Jessica E.; Bangsberg, David R.; Kaida, Angela; Matthews, Lynn T.Preventing unintended pregnancy is critical for women living with HIV (WLWH) to safely achieve their reproductive goals. Family planning services should support WLWH at risk of repeat unintended pregnancies. We examined the relationship between unintended pregnancy and subsequent contraception use among WLWH in Uganda. This was a retrospective analysis of data from a longitudinal cohort of individuals initiating antiretroviral therapy (ART), restricted to women with pregnancy (confirmed via urine β-hcg testing) between 2011–2013. The exposure of interest was intended vs unintended pregnancy, and the outcome was self-report of modern contraceptive use (hormonal methods, intrauterine device, sterilization, and/or consistent condom use) at 12 (range 6–18) months post-partum. A log-binomial model was used to estimate relative risks of modern contraceptive use post-partum based on intent of the index pregnancy, adjusted for age, socioeconomic status, education, relationship and HIV status of pregnancy partner, contraceptive use prior to pregnancy, years since HIV diagnosis, ART regimen, and CD4 cell count.Item Declining Prevalence of Probable Depression Among Patients Presenting for Antiretroviral Therapy in Rural Uganda: The Role of Early Treatment Initiation(AIDS and Behavior, 2015) Chan, Brian T.; Weiser, Sheri D.; Boum, Yap; Haberer, Jessica E.; Kembabazi, Annet; Hunt, Peter W.; Martin, Jeffrey N.; Mocello, A. Rain; Bangsberg, David R.; Tsai, Alexander C.Little is known about trends in depression at antiretroviral therapy (ART) initiation among people living with HIV (PLHIV) in low- and middle-income countries. We used data from an ongoing cohort of treatment -naı¨ve PLHIV in rural Uganda to estimate secular trends in depression among PLHIV at ART initiation. We fitted linear regression models with depression symptom severity as the outcome variable and year of cohort entry (2005–2012) as the explanatory variable, adjusting for socio-demographic variables and assessing physical health score, body mass index (BMI), and CD4 count as potential mediators of a secular trend in depression symptom severity. There was a statistically significant negative association between year of entry and depression symptom severity, suggesting a 3.1 % relative decline in the mean depression symptom severity score at ART initiation in each year of study recruitment after the first year. This trend remained statistically significant after inclusion of baseline socio demographic characteristics to the model and appeared to be driven by improved physical health scores, but not CD4 count or BMI.Item Disinhibition in Risky Sexual Behavior in Men, but Not Women, during Four Years of Antiretroviral Therapy in Rural, Southwestern Uganda(PLoS One, 2013) Kembabazi, Annet; Bajunirwe, Francis; Hunt, Peter W.; Martin, Jeffrey N.; Muzoora, Conrad; Haberer, Jessica E.; Bangsberg, David R.; Siedner, Mark J.In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy.We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count.506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29–39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74–0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14–1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92–1.67, p = 0.16).Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.Item Dissemination of Research Findings to Research Participants Living with HIV in Rural Uganda: Challenges and Rewards(PLoS Medicine, 2013) Baylor, Anna; Muzoora, Conrad; Bwana, Mwebsa; Kembabazi, Annet; Haberer, Jessica E.; Matthews, Lynn T.; Tsai, Alexander C.; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.Community participatory research emphasizes communication of study findings to research participants of vulnerable populations [1]. Most dissemination activities in sub-Saharan Africa have occurred after the completion (or termination) of randomized clinical trials of a defined intervention [2–4]. Sharing research findings with participants during observational research can avoid therapeutic misconception [5] as well as evaluate the validity of research involving knowledge, attitudes, or behavior through a ‘‘member check’’ procedure in which investigators conduct interviews regarding the relevancy and saliency of their findings [6]. Nonetheless, the communication of research findings to participants living with HIV enrolled in observational research in a rural sub- Saharan African setting is less straight forward and presents significant challenges respect to literacy, language, logistics, and confidentiality.Item The Dynamic Relationship Between Social Support and HIV-Related Stigma in Rural Uganda(Annals of Behavioral Medicine, 2014) Takada, Sae; Weiser, Sheri D.; Kumbakumba, Elias; Muzoora, Conrad; Martin, Jeffrey N.; Hunt, Peter W.; Haberer, Jessica E.; Kawuma, Annet; Bangsberg, David R.; Tsai, Alexander C.Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support. Purpose The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma. We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma. Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations. Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigmaItem Evidence for the Reliability and Validity of the Internalized AIDS-Related Stigma Scale in Rural Uganda(AIDS and Behavior, 2013) Tsai, Alexander C.; Weiser, Sheri D.; Steward, Wayne T.; Mukiibi, Nozmo F. B.; Kawuma, Annet; Kembabazi, Annet; Muzoora, Conrad; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.HIV infection remains highly stigmatized throughout sub-Saharan Africa despite the increasing availability of treatment. HIV-related stigma is commonly described to be highly prevalent in East Africa, but none of these studies have employed validated scales for measurement. We used data from 456 people living with HIV/ AIDS in rural Uganda to validate the six-item Internalized AIDS-Related Stigma Scale. The scale demonstrated acceptable internal consistency (Cronbach’s alpha = 0.73) and time stability. Exploratory factor analysis indicated the presence of a single factor. Construct validity was supported by observations that the scale was correlated with related constructs such as depression and mental health related quality of life. The scale was able to discriminate between groups of persons who were different in terms of treatment status and their experience of HIV-related self-blame. Taken together, these findings suggest that the Internalized AIDS-Related Stigma Scale may be a useful tool for socio-behavioral HIV research.Item High incidence of intended partner pregnancy among men living with HIV in rural Uganda: Implications for safer conception services(Journal of acquired immune deficiency syndromes, 2019) Kaida, Angela; Kabakyenga, Jerome; Bwana, Mwebesa; Bajunirwe, Francis; Muyindike, Winnie; Bennett, Kara; Kembabazi, Annet; Haberer, Jessica E.; Boum, Yap; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.; Matthews, Lynn T.Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy (ART) in Uganda.Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men’s sexual and reproductive health annually and repeated at time of reported pregnancy (2011–2015). We measured partner pregnancy incidence overall, by pregnancy intention, and by reported partner HIV-serostatus. We assessed viral suppression (≤400 copies/mL) during the peri-conception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy.Among 189 men, baseline median age was 39.9 years [IQR:34.7,47.0], years on ART was 3.9 [IQR:0.0,5.1], and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence=16.0/100 person-years); 45% with HIV-serodifferent partners. By three years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV-serostatus (p=0.75). 69% of pregnancies were intended, 18% wanted but mis-timed, and 8% unwanted. 78% of men were virally suppressed prior to pregnancy report. Men who were younger (aHR:0.94/year;95%CI:0.89–0.99), had incomplete primary education (aHR:2.95;95%CI:1.36–6.40), and reported fertility desires (aHR:2.25;95%CI:1.04–4.85) had higher probability of partner pregnancy.A high incidence of intended partner pregnancy highlights the need to address men’s reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV and one-quarter of men were not virally suppressed during peri-conception. Safer conception care provides opportunity to support men’s health and reproductive goals, while preventing HIV transmission to women and infants.Item HIV-infected women on antiretroviral treatment have increased mortality during pregnant and postpartum periods(AIDS (London, England), 2013) Matthews, Lynn T.; Kaida, Angela; Kanters, Steven; Byakwagamd, Helen; Mocello, A. Rain; Muzoora, Conrad; Kembabazi, Annet; Haberer, Jessica E.; Martin, Jeffrey N.; Bangsberg, David R.; Hunt, Peter W.To assess the impact of pregnancy on mortality among HIV-infected Ugandan women initiating ART. Prospective cohort study. HIV-infected women initiating ART in the Uganda AIDS Rural Treatment Outcomes study were assessed quarterly for self-reported pregnancy. The association between pregnancy and postpartum (‘pregnancy-related’) follow-up periods and mortality was assessed with Cox proportional hazards models adjusted for age, CD4 cell count, plasma HIV-1 RNA levels, and ART duration. Results: Three hundred and fifty-four women with median age 33 years (IQR: 27–37) and CD4 142 cells/ml (IQR: 82–213) were followed for a median of 4.0 years (IQR: 2.5–4.8) after ART initiation, with 3 and 7% loss-to-follow-up at years 1 and 5. One hundred and nine women experienced pregnancy. Five deaths occurred during pregnancy-related follow-up and 16 during nonpregnancy-related follow-up, for crude mortality rates during the first year after ART initiation of 12.57/100 PYs and 3.53/100 PYs (rate ratio 3.56, 95% CI: 0.97–11.07). In adjusted models, the impact of pregnancy related follow-up on mortality was highest at ART initiation (aHR: 21.48, 95% CI: 3.73–123.51), decreasing to 13.44 (95% CI 3.28–55.11) after 4 months, 8.28 (95% CI 2.38–28.88) after 8 months, 5.18 (95% CI: 1.36–19.71) after 1 year, and 1.25 (95% CI: 0.10–15.58) after 2 years on ART. Four of five maternal deaths occurred postpartum.Item Ideal Cardiovascular Health and Carotid Atherosclerosis in a Mixed Cohort of HIV-Infected and Uninfected Ugandans(AIDS research and human retroviruses, 2017) Feinstein, Matthew J.; Kim, June-Ho; Bibangambah, Prossy; Sentongo, Ruth; Martin, Jeffrey N.; Tsai, Alexander C.; Bangsberg, David R.; Hemphill, Linda; Triant, Virginia A.; Boum II, Yap; Hunt, Peter W.; Okello, Samson; Siedner, Mark J.Preventable cardiovascular disease (CVD) risk factors are responsible for the majority of CVD-related deaths, and are increasingly recognized as a cause of morbidity and mortality for HIV-infected persons taking antiretroviral therapy (ART). Simplified tools such as the American Heart Association’s ideal cardiovascular health (iCVH) construct may identify and prognosticate CVD risk in resource-limited settings. No studies have evaluated iCVH metrics in sub-Saharan Africa or among HIV-infected adults. Thus, the central aim of this study was to compare levels of iCVH metrics and their correlations with carotid atherosclerosis for HIV-infected adults versus uninfected controls in a well-phenotyped Ugandan cohort. We analyzed the prevalence of iCVH metrics in a mixed cohort of HIV-infected persons on stable ART and uninfected, population-based comparators in Mbarara, Uganda. We also assessed the validity of iCVH by correlating iCVH values with common carotid intima media thickness (CCIMT). HIV-infected persons had a mean of 4.9 (SD 1.1) iCVH metrics at ideal levels versus 4.3 (SD 1.2) for uninfected controls ( p = .002). This difference was largely driven by differences in blood pressure, blood glucose, and diet. In multivariable-adjusted linear regression models, each additional iCVH metric at an ideal level was associated with a significant 0.024mm decrease in CCIMT ( p < .001).HIV-infected persons on ART in rural Uganda had more iCVH metrics at ideal levels than uninfected persons. The difference appeared driven by factors that are putatively influenced by access to routine medical care. Composite scores of iCVH metrics were associated with subclinical atherosclerosis and more predictive of atherosclerosis for uninfected persons.Item Immunologic Pathways That Predict Mortality in HIV-Infected Ugandans Initiating Antiretroviral Therapy(The Journal of infectious diseases, 2017) Lee, Sulggi; Byakwaga, Helen; Boum, Yap; Burdo, Tricia H.; Williams, Kenneth C.; Lederman, Michael M.; Huang, Yong; Tracy, Russell P.; Cao, Huyen; Haberer, Jessica E.; Kembabazi, Annet; Bangsberg, David R.; Martin, Jeffrey N.; Hunt, Peter W.The plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated human immunodeficiency virus (HIV) disease in Ugandans as compared to US-based populations. Here, the KT ratio and T-cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. The month 6 KT ratio (adjusted hazard ratio [aHR], 2.74), soluble CD14 level (aHR, 2.32), interleukin 6 level (aHR, 2.34), and D-dimer level (aHR, 1.95) were associated with mortality occurring ≥6 months after ART initiation. The KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings.Item Impact of CD8R T-cell activation on CD4R T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy(AIDS (London, England), 2011) Hunt, Peter W.; Caoa, Huyen L.; Muzoora, Conrad; Ssewanyana, Isaac; Bennett, John; Emenyonu, Nneka; Kembabazi, Annet; Neilands, Torsten B.; Bangsberg, David R.; Deeks, Steven G.; Martin, Jeffrey N.To assess whether T-cell activation independently predicts the extent of CD4þ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART). Prospective cohort study. HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38þHLA-DRþ) T cells were measured every 3 months. Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/ml; and VL, 5.1 log10 copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre- ART CD8þ T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P¼0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8þ T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P¼0.048). Higher pre-ART CD8þ T-cell activation independently predicts slower CD4þ T-cell recovery and higher persistent CD8þ T-cell activation during ART mediated viral suppression independently predicts increased mortality among HIV infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.Item Increasing Prevalence of HIV Pretreatment Drug Resistance in Women But Not Men in Rural Uganda During 2005–2013(AIDS patient care and STDs, 2018) McCluskey, Suzanne M.; Lee, Guinevere Q.; Kamelian, Kimia; Kembabazi, Annet; Musinguzi, Nicholas; Bwana, Mwebesa B.; Muzoora, Conrad; Haberer, Jessica E.; Hunt, Peter W.; Martin, Jeffrey N.; Boum, Yap; Bangsberg, David R.; Harrigan, Richard; Siedner, Mark J.The prevalence of HIV pretreatment drug resistance (PDR) is increasing in sub-SaharanAfrica.We sought to describe correlates of PDR and evaluate effects of PDR on clinical outcomes in rural Uganda. We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, a cohort of antiretroviral therapy (ART)-naive adults with HIV (2005–2015). We performed resistance testing on pre-ART specimens. We defined PDR as any World Health Organization (WHO) 2009 surveillance drug resistance mutation and classified PDR level using the Stanford algorithm. We fit unadjusted and sex-stratified log binomial regression and Cox proportional hazardmodels to identify correlates of PDR and the impact of PDR on viral suppression, loss to follow-up (LTFU), and death. We analyzed data from 738 participants (median age 33 years, 69% female). Overall, prevalence of PDR was 3.5% (n = 26), owing mostly to resistance to non-nucleoside reverse transcriptase inhibitors. PDR increased over time in women (1.8% in those enrolling in clinic in 2001–2006, vs. 7.0% in 2007–2013; p = 0.006), but not in men (1.15% vs. 0.72%, p = 0.737). Lower pre-ART log10 HIV RNA was also associated with higher prevalence of PDR. We identified longer time to viral suppression among those with PDR compared with without PDR (0.5 and 0.3 years, respectively, p = 0.023), but there was no significant relationship with mortality or LTFU ( p = 0.139). We observed increasing rates of PDR in women in southwestern Uganda. Implications of this trend, particularly to prevention of mother-to-child transmission programs in the region, require attention due to delayed viral suppression among those with PDR.Item Internalized stigma, depressive symptoms, and the modifying role of antiretroviral therapy: A cohort study in rural Uganda(SSM-Mental Health, 2021) Bebell, Lisa M.; Kembabazi, Annet; Musinguzi, Nicholas; Martin, Jeffrey N.; Hunt, Peter W.; Boum, Yap; O'Laughlin, Kelli N.; Muzoora, Conrad; Haberer, Jessica E.; Mwebesa, Bosco Bwana; Bangsberg, David R.; Siedner, Mark J.; Tsai, Alexander C.Depression affects over 40% of people with HIV (PHIV) in low- and middle-income countries, and over half of PHIV report HIV related internalized stigma. However, few longitudinal studies of PHIV have examined the relationship between HIV-related stigma and depression. Data were analyzed from the 2007-15 Uganda AIDS Rural Treatment Outcomes (UARTO) Study, a cohort of 454 antiretroviral therapy (ART)-naïve PHIV (68% women) starting ART. Our primary outcome was depression symptom severity over the first two years of ART, measured using a locally adapted version of the Hopkins Symptom Checklist; our primary exposure was the 6-item Internalized AIDS-Related Stigma Scale. Both scores were measured at enrollment and at quarterly follow-up visits. We fit linear generalized estimating equations (GEE) regression models to estimate the association between stigma and depression symptom severity, adjusting for potential confounders. We included a stigma timeproduct term to assess the modifying effect of ART on the association between internalized stigma and depression symptom severity. UARTO participants had a median age of 32 years and median enrollment CD4 count of 217 cells/mm3. Both depression symptom severity and internalized stigma declined on ART, particularly during the first treatment year. In multivariable regression models, depression symptom severity was positively associated with internalized stigma (b ¼ 0.03; 95% confidence interval [CI], 0.02 to 0.04) and negatively associated with ART duration >6 months (b ¼ 0.16; 95% CI, 0.19 to 0.13). The estimated product term coefficient was negative and statistically significant (P ¼ 0.004), suggesting that the association between internalized stigma and depression symptom severity weakened over time on ART. Thus, in this large cohort of PHIV initiating ART in rural Uganda, depression symptom severity was associated with internalized stigma but the association declined with time on ART. These findings underscore the potential value of ART as a stigma reduction intervention for PHIV, particularly during early treatment.Item The Kynurenine Pathway of Tryptophan Catabolism, CD4+ T-Cell Recovery, and Mortality Among HIV-Infected Ugandans Initiating Antiretroviral Therapy(The Journal of infectious diseases, 2014) Byakwaga, Helen; Boum, Yap; Huang, Yong; Muzoora, Conrad; Kembabazi, Annet; Weiser, Sheri D.; Bennett, John; Cao, Huyen; Haberer, Jessica E.; Deeks, Steven G.; Bangsberg, David R.; McCune, Joseph M.; Martin, Jeffrey N.; Hunt, Peter W.Human immunodeficiency virus (HIV) infection–induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown. We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the “KT ratio”) in HIV-infected Ugandans before and during antiretroviral therapy (ART)–mediated viral suppression and its association with the rate of subsequent CD4+ T-cell count recovery and mortality. Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load (P < .001) and lipopolysaccharide level (P = .018), a lower CD4+ T-cell count (P < .001), and female sex (P = .047). Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for pre-ART CD4+ T-cell count, virus load, age, and sex, a higher month 12 KT ratio predicted a slower rate of subsequent CD4+ T-cell count recovery (P = .001). Thirty-nine participants died. After adjustment for pre-ART CD4+ T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio predicted increased mortality (P ≤ .016). The kynurenine pathway of tryptophan catabolism independently predicts poor CD4+ T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions.Item No Association Found Between Traditional Healer Use and Delayed Antiretroviral Initiation in Rural Uganda(AIDS and Behavior, 2013) Horwitz, Russell H.; Tsai, Alexander C.; Maling, Samuel; Bajunirwe, Francis; Haberer, Jessica E.; Emenyonu, Nneka; Muzoora, Conrad; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.Traditional healer and/or spiritual counselor (TH/SC) use has been associated with delays in HIV testing. We examined HIV-infected individuals in southwestern Uganda to test the hypothesis that TH/SC use was also associated with lower CD4 counts at antiretroviral therapy (ART) initiation. Approximately 450 individuals initiating ART through an HIV/AIDS clinic at the Mbarara University of Science and Technology (MUST) were recruited to participate. Patients were predominantly female, ranged in age from 18 to 75, and had a median CD4 count of 130. TH/SC use was not associated with lower CD4 cell count, but age and quality-of-life physical health summary score were associated with CD4 cell count at initiation while asset index was negatively associated with CD4 count at ART initiation. These findings suggest that TH/SC use does not delay initiation of ART.Item Prospective Study of the Mental Health Consequences of Sexual Violence Among Women Living With HIV in Rural Uganda(Journal of interpersonal violence, 2016) Tsai, Alexander C.; Wolfe, William R.; Kumbakumba, Elias; Kawuma, Annet; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.; Weiser, Sheri D.The association between sexual violence and depression is well known, but the temporal aspects of the association have not been well established. We analyzed data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed every 3 months for a median of 1.8 years of follow-up. The method of generalized estimating equations (GEE) was used to model the marginal expectation of depression symptom severity (Hopkins Symptom Checklist for Depression), mental health–related quality of life (MOS-HIV Mental Health Summary), and heavy drinking (Alcohol Use Disorders Identification Test) as a function of self-reported forced-sex victimization in the 3 months prior to interview.Item Relationship Power and Sexual Violence Among HIV-Positive Women in Rural Uganda(AIDS and Behavior, 2016) Conroy, Amy A.; Tsai, Alexander C.; Clark, Gina M.; Boum, Yap; Hatcher, Abigail M.; Kawuma, Annet; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.; Weiser, Sheri D.Gender-based power imbalances place women at significant risk for sexual violence, however, little research has examined this association among women living with HIV/AIDS. We performed a cross-sectional analysis of relationship power and sexual violence among HIV-positive women on anti-retroviral therapy in rural Uganda. Relationship power was measured using the Sexual Relationship Power Scale (SRPS), a validated measure consisting of two subscales: relationship control (RC) and decision-making dominance. We used multivariable logistic regression to test for associations between the SRPS and two dependent variables: recent forced se and transactional sex. Higher relationship power (full SRPS) was associated with reduced odds of forced sex (AOR = 0.24; 95 % CI 0.07–0.80; p = 0.020). The association between higher relationship power and transactional sex was strong and in the expected direction, but not statistically significant (AOR = 0.47; 95 % CI 0.18–1.22; p = 0.119). Higher RC was associated with reduced odds of both forced sex (AOR = 0.18; 95 % CI 0.06–0.59; p\0.01) and transactional sex (AOR = 0.38; 95 % CI 0.15–0.99; p = 0.048). Violence prevention interventions with HIV-positive women should consider approaches that increase women’s power in their relationships.