Winnie Muyindike | Mbarara University of Science and Technology (MUST) (original) (raw)
Papers by Winnie Muyindike
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
Aids Patient Care and Stds, Aug 1, 2017
2013 WHO guidelines for prevention of mother to child transmission recommend combination antiretr... more 2013 WHO guidelines for prevention of mother to child transmission recommend combination antiretroviral therapy (ART) for all pregnant women, regardless of CD4 count (Option B/B+). We conducted a retrospective analysis of data from a government-operated HIV clinic in Mbarara, Uganda before and after implementation of Option B+ to assess the impact on retention in care. We limited our analysis to women not on ART at the time of their first reported pregnancy with CD4 count >350. We fit regression models to estimate relationships between calendar period (Option A vs. Option B+) and the primary outcome of interest, retention in care. One thousand and sixty-two women were included in the analysis. Women were more likely to start ART within 6 months of pregnancy in the Option B+ period (68% vs. 7%, p < 0.0001) and had significantly greater increases in CD4 count 1 year after pregnancy (+172 vs.-5 cells, p < 0.001). However, there was no difference in the proportion of women retained in care 1 year after pregnancy (73% vs. 70%, p = 0.34). In models adjusted for age, distance to clinic, marital status, and CD4 count, Option B+ was associated with a nonsignificant 30% increased odds of retention in care at 1 year [adjusted odds ratio (AOR) = 1.30, 95% CI 0.98-1.73, p = 0.06]. After transition to an Option B+ program, pregnant women with CD4 count >350 were more likely to initiate combination therapy; however, interventions to mitigate losses from HIV care during pregnancy are needed to improve the health of women, children, and families.
Current Hiv/aids Reports, Jun 29, 2011
Alcohol consumption adds fuel to the HIV epidemic in sub-Saharan Africa (SSA). SSA has the highes... more Alcohol consumption adds fuel to the HIV epidemic in sub-Saharan Africa (SSA). SSA has the highest prevalence of HIV infection and heavy episodic drinking in the world. Alcohol consumption is associated with behaviors such as unprotected sex and poor medication adherence, and biological factors such as increased susceptibility to infection, comorbid conditions, and infectiousness, which may synergistically increase HIVacquisition and onward transmission. Few interventions to decrease alcohol consumption and alcohol-related sexual risk behaviors have been developed or implemented in SSA, and few HIV or health policies or services in SSA address alcohol consumption. Structural interventions, such as regulating the availability, price, and advertising of alcohol, are challenging to implement due to the preponderance of homemade alcohol and beverage industry resistance. This article reviews the current knowledge on how alcohol impacts the HIV epidemic in SSA, summarizes current interventions and policies, and identifies areas for increased research and development.
Journal of Acquired Immune Deficiency Syndromes, Apr 1, 2018
Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PL... more Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV), and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in three high TB/HIV burden countries. Methods: We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included non-fatal toxicity, fatal toxicity, life expectancy, TB cases and TB death. Results: In this simulation, 6 months of IPT+ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT+ ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6, and 415/1000
Aids Patient Care and Stds, 2016
The objectives of this study were to determine the epidemiology and correlates of cardiovascular ... more The objectives of this study were to determine the epidemiology and correlates of cardiovascular disease (CVD) risk among Ugandans on first-line antiretroviral therapy (ART). We conducted a cross-sectional study at an HIV clinic in southwestern Uganda. We enrolled adult patients on non-nucleoside-based ART regimens for a minimum of 2 years. We collected anthropometric and clinical measurements, smoking history, and blood for fasting lipid profile and blood sugar (FBS). Outcomes of interest were (1) presence of metabolic syndrome (at least two of the following: FBS >100 mg/dL, blood pressure of ‡130/85 mmHg, triglycerides ‡150 mg/dL, HDL <40 mg/DL, or waist circumference ‡94 cm in males or ‡80 cm in females); and (2) a Framingham score correlating to >5% 10year CVD risk. Of the 250 participants enrolled, metabolic syndrome was detected in 145/250 (58%) of participants (62% in females and 50% in males). Forty-three participants (17%) had a Framingham risk correlating to a 5% or greater risk for CVD within 10 years (26% in males and 13% in females). In multivariate analyses, being female (AOR 3.13; 95% CI: 1.0-9.70; p = 0.04) and over 40 years of age (AOR 1.78; 95% CI: 1.00-3.17; p = 0.05) was independently associated with having metabolic syndrome. We found no independent risk factors for a Framingham risk score 10-year risk exceeding 5%, or associations between ART regimen and CVD risk profiles. We conclude that metabolic abnormalities are common among patients on first-line ART in rural Uganda, and appear to be more common in women than men.
Sexually Transmitted Diseases
Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) wher... more Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) where laboratory diagnostic access is limited. Advancements in point-of-care testing (POC) technology have the potential to bring STI testing to many RLSs. We define POC as performed near the patient and with results readily available to inform clinical practice. The World Health Organization Special Programme for Research and Training in Tropical Diseases further outlines desirable POC characteristics with the REASSURED criteria. Despite advantages related to immediate test-and-treat care, integrating POC into RLS health care systems can present challenges that preclude reliance on these tests. In 2018, we incorporated molecular near-POC for chlamydia, gonorrhea, and trichomoniasis and SDBioline treponemal immunochromatographic testing confirmed by rapid plasma reagin for syphilis diagnosis at the Mbarara University of Science and Technology Research Laboratory in rural southwestern Uganda....
Topics in antiviral medicine, 2021
Background: The fixed-dose combination of tenofovir (TDF), lamivudine (3TC), and dolutegravir (TL... more Background: The fixed-dose combination of tenofovir (TDF), lamivudine (3TC), and dolutegravir (TLD) is now preferred first-line antiretroviral therapy (ART) for most adults with HIV in Sub-Saharan Africa. Yet, concerns remain about durability of TLD with high circulating resistance to 3TC and TDF and metabolic abnormalities observed in clinical trials. Limited programmatic data are available to describe the success of the TLD transition in the region. Methods: We established the DISCO cohort to quantify viral suppression and regimen tolerability during the TLD transition. We prospectively enrolled adults from public clinics in Uganda and South Africa who had been on non-nucleoside reverse transcriptase inhibitor-based ART for ≥6 months and were programmatically switched to TLD. We obtained demographics, medical history data, and plasma specimens at enrollment and week 24. We conducted retrospective HIV-1 RNA viral load (VL) testing using the Cepheid GeneXpert platform. Though both s...
Background: Little is known about the survival of patients with esophageal squamous cell cancer i... more Background: Little is known about the survival of patients with esophageal squamous cell cancer in resource limited settings.Objectives: We sought to determine the incidence of one-year all-cause mortality and age-standardized mortality rates for esophageal squamous cell carcinoma in Uganda.Methods: Prospective cohort of 92 participants with histologically confirmed esophageal squamous cell cancer at Mbarara Regional Referral Hospital, southwestern Uganda. Participants were enrolled between January 2018 and March 2020 and followed until death. We used Kaplan-Meier methods to determine all-cause mortality and median survival time; Cox regression to determine predictors of survival; and determined age-standardized mortality rates (SMR) using the WHO standard population. Results: All 92 participants contributed a total 353.8 months at risk, 89 (96.7%) died representing an incidence rate of 251.5 (95% CI 204.3, 309.6) per 1000 person-months. The difference in the one-year risk of all-ca...
BMC Infectious Diseases, 2021
Background Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settin... more Background Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. Methods Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid ...
Journal of Global Health Reports, 2020
Background The burden of non-communicable diseases (NCDs) is rapidly increasing in low- and middl... more Background The burden of non-communicable diseases (NCDs) is rapidly increasing in low- and middle-income countries, but remains largely unknown among people living with HIV (PLWH) in most sub-Saharan African countries. Methods We estimated the proportion of PLWH in Uganda with raised blood pressure and high total cholesterol, and used a modified cardiovascular disease (CVD) risk prediction model (Globorisk) to assess the 10-year risk of atherosclerotic cardiovascular disease using individual-level data on cardiometabolic risk factors, population-level data on HIV prevalence and ART coverage, and the impact of HIV on blood pressure and cholesterol. Results Among PLWH aged 30 to 69 years, the prevalence of raised blood pressure was 30% (95% uncertainty range, UR=27-33%) in women and 26% in men (95% UR=23-29%). The predicted mean 10-year CVD risk was 5% for HIV-infected women, and 6% for HIV-infected men. Five percent (n=41,000) of PLWH may experience a CVD event from 2016 to 2025 wit...
Background Treatment monitoring of multidrug-resistant (MDR) and extensively drug-resistant tuber... more Background Treatment monitoring of multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. Methods Small hair samples were collected from participants at various timepoints during directly-observed MDR/XDR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed an LC-MS/MS index panel assay including isoniazid, ethambutol, pyrazinamide, levofloxacin, moxifloxacin, ethionamide, prothionamide, linezolid, clofazimine, pretomanid, and bedaquiline against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort)...
PLOS ONE, 2021
A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of... more A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of active tuberculosis (TB); however, it is unclear whether 3HP should be provided by directly observed therapy (DOT) or self-administered therapy (SAT). In addition, the introduction of patient informed choice between delivery modalities may have a positive impact on factors leading to treatment completion. The authors randomized 252 participants with HIV to a hypothetical scenario of providing preventive therapy by either DOT or an informed choice between DOT and SAT. Out of 104 participants who were randomized to a choice between DOT and SAT, 103 chose therapy by SAT. Participants rated their level of confidence and intention to complete therapy. Compared to those assigned to the DOT scenario, patients assigned to the choice scenario expressed greater confidence and intention to complete preventive therapy. Convenience and travel required to complete 3HP therapy were important factors i...
PLOS Medicine, Feb 16, 2023
Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive ... more Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. Methods and findings We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided
Alcoholism: Clinical and Experimental Research, Aug 11, 2022
BackgroundBoth human immunodeficiency virus (HIV) infection and alcohol use predispose to autonom... more BackgroundBoth human immunodeficiency virus (HIV) infection and alcohol use predispose to autonomic/sensory neuropathy, imbalance symptoms, and cognitive impairment—conditions associated with a greater risk of falls—yet it is unclear how to identify people with HIV (PWH) whose drinking is associated with falls. Research on alcohol and falls using the same instruments in different countries could help to specify the level of alcohol use associated with fall risk. We examined whether a consumption‐based measure (the Alcohol Use Disorders Identification Test‐Consumption [AUDIT‐C]) and/or a symptom‐based measure (DSM‐5 criteria for alcohol use disorder [AUD]) are associated with sustaining a fall among PWH in St Petersburg, Russia and Boston, Massachusetts in the United States.MethodsSeparate multivariate logistic regressions were used for each cohort to examine cross‐sectional associations for each alcohol measure predicting fall. Potential confounders included physical functioning, depressive symptoms, and other substance use (measured with the Addiction Severity Index).ResultsA fall was reported by 35% (87/251) of the sample in Boston and 12% (46/400) in St Petersburg. Each additional AUD criterion—but not higher AUDIT‐C score—was significantly associated with a fall in both Boston (odds ratio [OR] = 1.10; 95% confidence interval [CI] 1.02, 1.18) and St Petersburg (adjusted OR AOR = 1.10; 95% CI 1.02, 1.18). Heavy alcohol use (>6 drinks/occasion, any vs. none) was associated with more than twice the odds of a fall (AOR = 2.24; 95% CI 1.21, 4.13) in Boston.ConclusionsThese findings suggest that while fall risk may vary by setting and population, heavy alcohol use and AUD symptom severity are potential targets for interventions to prevent falls. Studies in diverse global settings advance our understanding of the relationship between alcohol and falls in PWH.
Addiction, Nov 5, 2015
We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes... more We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes after HIV care entry overall and by several factors. We also compared using phosphatidylethanol (PEth, an alcohol biomarker) to augment self-report to using selfreport alone. Design: Prospective one-year observational cohort study with quarterly visits. Setting: Large rural HIV clinic in Mbarara, Uganda. Participants: 208 adults (89 women and 119 men) entering HIV care, reporting any prior year alcohol consumption. Measurements: Unhealthy drinking was PEth+ (≥50 ng/ml) or Alcohol Use Disorders Test-Consumption+ (AUDIT-C+, over 3 months, women ≥3; men ≥4). We calculated adjusted odds ratios (AOR) for unhealthy drinking per month since baseline, and interactions of month since baseline with perceived health, number of HIV symptoms, anti-retroviral therapy (ART), gender, and self-reported prior unhealthy alcohol use.
International Journal of Std & Aids, Jun 30, 2022
Background We provided sexually transmitted infection (STI) screening and facilitated partner not... more Background We provided sexually transmitted infection (STI) screening and facilitated partner notification and treatment among women participating in a periconception HIV prevention program in southwestern Uganda to understand follow-up STI incidence. Methods Women at-risk for HIV exposure while planning for pregnancy completed laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis at enrollment and 6 months of follow-up and/or incident pregnancy; facilitated partner notification and treatment were offered for those with positive tests. We performed a logistic regression to determine correlates of follow-up STI. Results Ninety-four participants completed enrollment STI screening with a median age of 29 (IQR 26–34); 23 (24%) had ≥1 STI. Of the 23 participants with enrollment STI(s), all completed treatment and 19 (83%) returned for follow-up; 18 (78%) reported delivering partner notification cards and discussing STIs with partner(s), and 14 (61%) reported all partners received STI treatment. Of the 81 (86%) who successfully completed follow-up STI screening, 17 (21%) had ≥1 STI. The STI incidence rate was 29.0 per 100 person-years. In univariable regression analysis, enrollment STI, younger age, less education, and alcohol consumption were all significantly associated with follow-up STI. Conclusions We demonstrated high enrollment and follow-up STI rates and moderate participant-reported partner treatment among women planning for pregnancy in Uganda despite partner notification and treatment. Novel STI partner notification and treatment interventions are needed to decrease the STI burden, especially among women planning for and with pregnancy.
Aids Care-psychological and Socio-medical Aspects of Aids/hiv, Feb 16, 2018
HIV infection may increase risk of postpartum infection and infection-related mortality. We hypot... more HIV infection may increase risk of postpartum infection and infection-related mortality. We hypothesized that postpartum infection incidence and attributable mortality in Mbarara, Uganda would be higher in HIV-infected than HIV-uninfected women. We performed a prospective cohort study of 4,231 women presenting to a regional referral hospital in 2015 for delivery or postpartum care. All febrile or hypothermic women, and a subset of randomly selected normothermic women were followed during hospitalization and with 6-week postpartum phone interviews. The primary outcome was in-hospital postpartum infection. Secondary outcomes included in-hospital complications (mortality, re-operation, intensive care unit transfer, need for imaging or blood transfusion) and 6-week mortality. We performed multivariable regression analyses to estimate adjusted differences in each outcome by HIV serostatus. Mean age was 25.2 years and 481 participants (11%) were HIV-infected. Median CD4+ count was 487 (IQR 325, 696) cells/mm 3 , and 90% of HIV-infected women (193/215 selected for in-depth survey) were on antiretroviral therapy. Overall, 5% (205/4231) of women developed fever or hypothermia. Cumulative inhospital postpartum infection incidence was 2.0% and did not differ by HIV status (aOR 1.4, 95% CI 0.6-3.3, P=0.49). However, more HIV-infected women developed postpartum complications (4.4% vs. 1.2%, P=0.001). In-hospital mortality was rare (2/1,768, 0.1%), and remained so at 6 weeks (4/1526, 0.3%), without differences by HIV serostatus (P=1.0 and 0.31, respectively). For women in rural Uganda with high rates of antiretroviral therapy coverage, HIV infection did not predict postpartum infection or mortality, but was associated with increased risk of postpartum complications.
Open Forum Infectious Diseases, 2017
Background. Combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected... more Background. Combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected pregnant women reduces the maternal-to-child transmission (MTCT) rate from a baseline of 25% to less than 2% when the HIV viral load (VL) is <1,000 copies/mL. The traditional cART is composed of 2 nucleoside reverse transcriptase inhibitor (NRTI-) and 1 protease inhibitor (PI)-class drugs. There is limited information on the effects of VL reduction in pregnancy with alternative cART modalities containing either an integrase strand transfer inhibitor (INSTI) or a non-NRTI (nNRTI). Objective: We sought to compare the HIV VL near delivery in HIV-infected pregnant women receiving 2 NRTI plus 1 PI (traditional cART) to those receiving 2 NRTI plus 1 INSTI or 1 nNRTI (alternative cART). Methods. Prospective cohort study of pregnant HIV-infected women from 2010 through 2016 receiving care in our high-risk obstetric infectious disease clinic. Women were included if they had at least 2 VL (before and after intervention) obtained during pregnancy. Our primary outcome was the rate of VL <1,000 copies/ mL near delivery. Results. We collected data in 274 subjects (traditional cART=156, alternative cART=118). After adjusting for confounders, the rate of VL <1,000 copies/mL near delivery was comparable among women receiving the traditional treatment (121/156, 77.6%) to the alternative cART (101/118, 85.6%); P = 0.2765, RR 1.474 (0.733-2.967). More women in the alternative cART group (66.9%) had undetectable VL near delivery compared with the traditional cART group (46.1%); P = 0.0103, RR 2.002, 95% CI 1.178-3.403. There were 5 cases (1.8%) of MTCT: 1 in the traditional cART group and 4 in 1 in the alternative cART group. Conclusion. After adjusting for confounders, our cohort of women receiving either traditional or alternative cART regimens achieved similar rate of HIV VL <1,000 copies/mL near delivery. Further studies are needed to replicate our findings. Disclosures. All authors: No reported disclosures.
PLOS ONE, Oct 25, 2018
Background Preventing unintended pregnancy is critical for women living with HIV (WLWH) to safely... more Background 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. Study design 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. Results Among 455 women, 110 women reported 110 incident pregnancies with report on intent. Women had a baseline median age of 29 years, baseline CD4 count 403 cells/mm 3 , and were living with HIV for 3.8 years. Fifty pregnancies (45%) were reported as unintended and 60 (55%) as intended. Postpartum, 64% of women with unintended and 51% with intended
Alcoholism: Clinical and Experimental Research, May 7, 2021
BackgroundObjective measurement of alcohol consumption is important for clinical care and researc... more BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self‐reported alcohol use, we conducted an individual participant data (IPD) meta‐analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self‐reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1‐step IPD meta‐analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index—BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger‐prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self‐reported alcohol use using the AUDIT‐C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT‐C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases
Aids Patient Care and Stds, Aug 1, 2017
2013 WHO guidelines for prevention of mother to child transmission recommend combination antiretr... more 2013 WHO guidelines for prevention of mother to child transmission recommend combination antiretroviral therapy (ART) for all pregnant women, regardless of CD4 count (Option B/B+). We conducted a retrospective analysis of data from a government-operated HIV clinic in Mbarara, Uganda before and after implementation of Option B+ to assess the impact on retention in care. We limited our analysis to women not on ART at the time of their first reported pregnancy with CD4 count >350. We fit regression models to estimate relationships between calendar period (Option A vs. Option B+) and the primary outcome of interest, retention in care. One thousand and sixty-two women were included in the analysis. Women were more likely to start ART within 6 months of pregnancy in the Option B+ period (68% vs. 7%, p < 0.0001) and had significantly greater increases in CD4 count 1 year after pregnancy (+172 vs.-5 cells, p < 0.001). However, there was no difference in the proportion of women retained in care 1 year after pregnancy (73% vs. 70%, p = 0.34). In models adjusted for age, distance to clinic, marital status, and CD4 count, Option B+ was associated with a nonsignificant 30% increased odds of retention in care at 1 year [adjusted odds ratio (AOR) = 1.30, 95% CI 0.98-1.73, p = 0.06]. After transition to an Option B+ program, pregnant women with CD4 count >350 were more likely to initiate combination therapy; however, interventions to mitigate losses from HIV care during pregnancy are needed to improve the health of women, children, and families.
Current Hiv/aids Reports, Jun 29, 2011
Alcohol consumption adds fuel to the HIV epidemic in sub-Saharan Africa (SSA). SSA has the highes... more Alcohol consumption adds fuel to the HIV epidemic in sub-Saharan Africa (SSA). SSA has the highest prevalence of HIV infection and heavy episodic drinking in the world. Alcohol consumption is associated with behaviors such as unprotected sex and poor medication adherence, and biological factors such as increased susceptibility to infection, comorbid conditions, and infectiousness, which may synergistically increase HIVacquisition and onward transmission. Few interventions to decrease alcohol consumption and alcohol-related sexual risk behaviors have been developed or implemented in SSA, and few HIV or health policies or services in SSA address alcohol consumption. Structural interventions, such as regulating the availability, price, and advertising of alcohol, are challenging to implement due to the preponderance of homemade alcohol and beverage industry resistance. This article reviews the current knowledge on how alcohol impacts the HIV epidemic in SSA, summarizes current interventions and policies, and identifies areas for increased research and development.
Journal of Acquired Immune Deficiency Syndromes, Apr 1, 2018
Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PL... more Background: Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV), and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in three high TB/HIV burden countries. Methods: We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included non-fatal toxicity, fatal toxicity, life expectancy, TB cases and TB death. Results: In this simulation, 6 months of IPT+ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT+ ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6, and 415/1000
Aids Patient Care and Stds, 2016
The objectives of this study were to determine the epidemiology and correlates of cardiovascular ... more The objectives of this study were to determine the epidemiology and correlates of cardiovascular disease (CVD) risk among Ugandans on first-line antiretroviral therapy (ART). We conducted a cross-sectional study at an HIV clinic in southwestern Uganda. We enrolled adult patients on non-nucleoside-based ART regimens for a minimum of 2 years. We collected anthropometric and clinical measurements, smoking history, and blood for fasting lipid profile and blood sugar (FBS). Outcomes of interest were (1) presence of metabolic syndrome (at least two of the following: FBS >100 mg/dL, blood pressure of ‡130/85 mmHg, triglycerides ‡150 mg/dL, HDL <40 mg/DL, or waist circumference ‡94 cm in males or ‡80 cm in females); and (2) a Framingham score correlating to >5% 10year CVD risk. Of the 250 participants enrolled, metabolic syndrome was detected in 145/250 (58%) of participants (62% in females and 50% in males). Forty-three participants (17%) had a Framingham risk correlating to a 5% or greater risk for CVD within 10 years (26% in males and 13% in females). In multivariate analyses, being female (AOR 3.13; 95% CI: 1.0-9.70; p = 0.04) and over 40 years of age (AOR 1.78; 95% CI: 1.00-3.17; p = 0.05) was independently associated with having metabolic syndrome. We found no independent risk factors for a Framingham risk score 10-year risk exceeding 5%, or associations between ART regimen and CVD risk profiles. We conclude that metabolic abnormalities are common among patients on first-line ART in rural Uganda, and appear to be more common in women than men.
Sexually Transmitted Diseases
Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) wher... more Most sexually transmitted infections (STIs) are acquired in resource-limited settings (RLSs) where laboratory diagnostic access is limited. Advancements in point-of-care testing (POC) technology have the potential to bring STI testing to many RLSs. We define POC as performed near the patient and with results readily available to inform clinical practice. The World Health Organization Special Programme for Research and Training in Tropical Diseases further outlines desirable POC characteristics with the REASSURED criteria. Despite advantages related to immediate test-and-treat care, integrating POC into RLS health care systems can present challenges that preclude reliance on these tests. In 2018, we incorporated molecular near-POC for chlamydia, gonorrhea, and trichomoniasis and SDBioline treponemal immunochromatographic testing confirmed by rapid plasma reagin for syphilis diagnosis at the Mbarara University of Science and Technology Research Laboratory in rural southwestern Uganda....
Topics in antiviral medicine, 2021
Background: The fixed-dose combination of tenofovir (TDF), lamivudine (3TC), and dolutegravir (TL... more Background: The fixed-dose combination of tenofovir (TDF), lamivudine (3TC), and dolutegravir (TLD) is now preferred first-line antiretroviral therapy (ART) for most adults with HIV in Sub-Saharan Africa. Yet, concerns remain about durability of TLD with high circulating resistance to 3TC and TDF and metabolic abnormalities observed in clinical trials. Limited programmatic data are available to describe the success of the TLD transition in the region. Methods: We established the DISCO cohort to quantify viral suppression and regimen tolerability during the TLD transition. We prospectively enrolled adults from public clinics in Uganda and South Africa who had been on non-nucleoside reverse transcriptase inhibitor-based ART for ≥6 months and were programmatically switched to TLD. We obtained demographics, medical history data, and plasma specimens at enrollment and week 24. We conducted retrospective HIV-1 RNA viral load (VL) testing using the Cepheid GeneXpert platform. Though both s...
Background: Little is known about the survival of patients with esophageal squamous cell cancer i... more Background: Little is known about the survival of patients with esophageal squamous cell cancer in resource limited settings.Objectives: We sought to determine the incidence of one-year all-cause mortality and age-standardized mortality rates for esophageal squamous cell carcinoma in Uganda.Methods: Prospective cohort of 92 participants with histologically confirmed esophageal squamous cell cancer at Mbarara Regional Referral Hospital, southwestern Uganda. Participants were enrolled between January 2018 and March 2020 and followed until death. We used Kaplan-Meier methods to determine all-cause mortality and median survival time; Cox regression to determine predictors of survival; and determined age-standardized mortality rates (SMR) using the WHO standard population. Results: All 92 participants contributed a total 353.8 months at risk, 89 (96.7%) died representing an incidence rate of 251.5 (95% CI 204.3, 309.6) per 1000 person-months. The difference in the one-year risk of all-ca...
BMC Infectious Diseases, 2021
Background Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settin... more Background Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. Methods Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid ...
Journal of Global Health Reports, 2020
Background The burden of non-communicable diseases (NCDs) is rapidly increasing in low- and middl... more Background The burden of non-communicable diseases (NCDs) is rapidly increasing in low- and middle-income countries, but remains largely unknown among people living with HIV (PLWH) in most sub-Saharan African countries. Methods We estimated the proportion of PLWH in Uganda with raised blood pressure and high total cholesterol, and used a modified cardiovascular disease (CVD) risk prediction model (Globorisk) to assess the 10-year risk of atherosclerotic cardiovascular disease using individual-level data on cardiometabolic risk factors, population-level data on HIV prevalence and ART coverage, and the impact of HIV on blood pressure and cholesterol. Results Among PLWH aged 30 to 69 years, the prevalence of raised blood pressure was 30% (95% uncertainty range, UR=27-33%) in women and 26% in men (95% UR=23-29%). The predicted mean 10-year CVD risk was 5% for HIV-infected women, and 6% for HIV-infected men. Five percent (n=41,000) of PLWH may experience a CVD event from 2016 to 2025 wit...
Background Treatment monitoring of multidrug-resistant (MDR) and extensively drug-resistant tuber... more Background Treatment monitoring of multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. Methods Small hair samples were collected from participants at various timepoints during directly-observed MDR/XDR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed an LC-MS/MS index panel assay including isoniazid, ethambutol, pyrazinamide, levofloxacin, moxifloxacin, ethionamide, prothionamide, linezolid, clofazimine, pretomanid, and bedaquiline against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort)...
PLOS ONE, 2021
A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of... more A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of active tuberculosis (TB); however, it is unclear whether 3HP should be provided by directly observed therapy (DOT) or self-administered therapy (SAT). In addition, the introduction of patient informed choice between delivery modalities may have a positive impact on factors leading to treatment completion. The authors randomized 252 participants with HIV to a hypothetical scenario of providing preventive therapy by either DOT or an informed choice between DOT and SAT. Out of 104 participants who were randomized to a choice between DOT and SAT, 103 chose therapy by SAT. Participants rated their level of confidence and intention to complete therapy. Compared to those assigned to the DOT scenario, patients assigned to the choice scenario expressed greater confidence and intention to complete preventive therapy. Convenience and travel required to complete 3HP therapy were important factors i...
PLOS Medicine, Feb 16, 2023
Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive ... more Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. Methods and findings We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided
Alcoholism: Clinical and Experimental Research, Aug 11, 2022
BackgroundBoth human immunodeficiency virus (HIV) infection and alcohol use predispose to autonom... more BackgroundBoth human immunodeficiency virus (HIV) infection and alcohol use predispose to autonomic/sensory neuropathy, imbalance symptoms, and cognitive impairment—conditions associated with a greater risk of falls—yet it is unclear how to identify people with HIV (PWH) whose drinking is associated with falls. Research on alcohol and falls using the same instruments in different countries could help to specify the level of alcohol use associated with fall risk. We examined whether a consumption‐based measure (the Alcohol Use Disorders Identification Test‐Consumption [AUDIT‐C]) and/or a symptom‐based measure (DSM‐5 criteria for alcohol use disorder [AUD]) are associated with sustaining a fall among PWH in St Petersburg, Russia and Boston, Massachusetts in the United States.MethodsSeparate multivariate logistic regressions were used for each cohort to examine cross‐sectional associations for each alcohol measure predicting fall. Potential confounders included physical functioning, depressive symptoms, and other substance use (measured with the Addiction Severity Index).ResultsA fall was reported by 35% (87/251) of the sample in Boston and 12% (46/400) in St Petersburg. Each additional AUD criterion—but not higher AUDIT‐C score—was significantly associated with a fall in both Boston (odds ratio [OR] = 1.10; 95% confidence interval [CI] 1.02, 1.18) and St Petersburg (adjusted OR AOR = 1.10; 95% CI 1.02, 1.18). Heavy alcohol use (>6 drinks/occasion, any vs. none) was associated with more than twice the odds of a fall (AOR = 2.24; 95% CI 1.21, 4.13) in Boston.ConclusionsThese findings suggest that while fall risk may vary by setting and population, heavy alcohol use and AUD symptom severity are potential targets for interventions to prevent falls. Studies in diverse global settings advance our understanding of the relationship between alcohol and falls in PWH.
Addiction, Nov 5, 2015
We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes... more We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes after HIV care entry overall and by several factors. We also compared using phosphatidylethanol (PEth, an alcohol biomarker) to augment self-report to using selfreport alone. Design: Prospective one-year observational cohort study with quarterly visits. Setting: Large rural HIV clinic in Mbarara, Uganda. Participants: 208 adults (89 women and 119 men) entering HIV care, reporting any prior year alcohol consumption. Measurements: Unhealthy drinking was PEth+ (≥50 ng/ml) or Alcohol Use Disorders Test-Consumption+ (AUDIT-C+, over 3 months, women ≥3; men ≥4). We calculated adjusted odds ratios (AOR) for unhealthy drinking per month since baseline, and interactions of month since baseline with perceived health, number of HIV symptoms, anti-retroviral therapy (ART), gender, and self-reported prior unhealthy alcohol use.
International Journal of Std & Aids, Jun 30, 2022
Background We provided sexually transmitted infection (STI) screening and facilitated partner not... more Background We provided sexually transmitted infection (STI) screening and facilitated partner notification and treatment among women participating in a periconception HIV prevention program in southwestern Uganda to understand follow-up STI incidence. Methods Women at-risk for HIV exposure while planning for pregnancy completed laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis at enrollment and 6 months of follow-up and/or incident pregnancy; facilitated partner notification and treatment were offered for those with positive tests. We performed a logistic regression to determine correlates of follow-up STI. Results Ninety-four participants completed enrollment STI screening with a median age of 29 (IQR 26–34); 23 (24%) had ≥1 STI. Of the 23 participants with enrollment STI(s), all completed treatment and 19 (83%) returned for follow-up; 18 (78%) reported delivering partner notification cards and discussing STIs with partner(s), and 14 (61%) reported all partners received STI treatment. Of the 81 (86%) who successfully completed follow-up STI screening, 17 (21%) had ≥1 STI. The STI incidence rate was 29.0 per 100 person-years. In univariable regression analysis, enrollment STI, younger age, less education, and alcohol consumption were all significantly associated with follow-up STI. Conclusions We demonstrated high enrollment and follow-up STI rates and moderate participant-reported partner treatment among women planning for pregnancy in Uganda despite partner notification and treatment. Novel STI partner notification and treatment interventions are needed to decrease the STI burden, especially among women planning for and with pregnancy.
Aids Care-psychological and Socio-medical Aspects of Aids/hiv, Feb 16, 2018
HIV infection may increase risk of postpartum infection and infection-related mortality. We hypot... more HIV infection may increase risk of postpartum infection and infection-related mortality. We hypothesized that postpartum infection incidence and attributable mortality in Mbarara, Uganda would be higher in HIV-infected than HIV-uninfected women. We performed a prospective cohort study of 4,231 women presenting to a regional referral hospital in 2015 for delivery or postpartum care. All febrile or hypothermic women, and a subset of randomly selected normothermic women were followed during hospitalization and with 6-week postpartum phone interviews. The primary outcome was in-hospital postpartum infection. Secondary outcomes included in-hospital complications (mortality, re-operation, intensive care unit transfer, need for imaging or blood transfusion) and 6-week mortality. We performed multivariable regression analyses to estimate adjusted differences in each outcome by HIV serostatus. Mean age was 25.2 years and 481 participants (11%) were HIV-infected. Median CD4+ count was 487 (IQR 325, 696) cells/mm 3 , and 90% of HIV-infected women (193/215 selected for in-depth survey) were on antiretroviral therapy. Overall, 5% (205/4231) of women developed fever or hypothermia. Cumulative inhospital postpartum infection incidence was 2.0% and did not differ by HIV status (aOR 1.4, 95% CI 0.6-3.3, P=0.49). However, more HIV-infected women developed postpartum complications (4.4% vs. 1.2%, P=0.001). In-hospital mortality was rare (2/1,768, 0.1%), and remained so at 6 weeks (4/1526, 0.3%), without differences by HIV serostatus (P=1.0 and 0.31, respectively). For women in rural Uganda with high rates of antiretroviral therapy coverage, HIV infection did not predict postpartum infection or mortality, but was associated with increased risk of postpartum complications.
Open Forum Infectious Diseases, 2017
Background. Combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected... more Background. Combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected pregnant women reduces the maternal-to-child transmission (MTCT) rate from a baseline of 25% to less than 2% when the HIV viral load (VL) is <1,000 copies/mL. The traditional cART is composed of 2 nucleoside reverse transcriptase inhibitor (NRTI-) and 1 protease inhibitor (PI)-class drugs. There is limited information on the effects of VL reduction in pregnancy with alternative cART modalities containing either an integrase strand transfer inhibitor (INSTI) or a non-NRTI (nNRTI). Objective: We sought to compare the HIV VL near delivery in HIV-infected pregnant women receiving 2 NRTI plus 1 PI (traditional cART) to those receiving 2 NRTI plus 1 INSTI or 1 nNRTI (alternative cART). Methods. Prospective cohort study of pregnant HIV-infected women from 2010 through 2016 receiving care in our high-risk obstetric infectious disease clinic. Women were included if they had at least 2 VL (before and after intervention) obtained during pregnancy. Our primary outcome was the rate of VL <1,000 copies/ mL near delivery. Results. We collected data in 274 subjects (traditional cART=156, alternative cART=118). After adjusting for confounders, the rate of VL <1,000 copies/mL near delivery was comparable among women receiving the traditional treatment (121/156, 77.6%) to the alternative cART (101/118, 85.6%); P = 0.2765, RR 1.474 (0.733-2.967). More women in the alternative cART group (66.9%) had undetectable VL near delivery compared with the traditional cART group (46.1%); P = 0.0103, RR 2.002, 95% CI 1.178-3.403. There were 5 cases (1.8%) of MTCT: 1 in the traditional cART group and 4 in 1 in the alternative cART group. Conclusion. After adjusting for confounders, our cohort of women receiving either traditional or alternative cART regimens achieved similar rate of HIV VL <1,000 copies/mL near delivery. Further studies are needed to replicate our findings. Disclosures. All authors: No reported disclosures.
PLOS ONE, Oct 25, 2018
Background Preventing unintended pregnancy is critical for women living with HIV (WLWH) to safely... more Background 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. Study design 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. Results Among 455 women, 110 women reported 110 incident pregnancies with report on intent. Women had a baseline median age of 29 years, baseline CD4 count 403 cells/mm 3 , and were living with HIV for 3.8 years. Fifty pregnancies (45%) were reported as unintended and 60 (55%) as intended. Postpartum, 64% of women with unintended and 51% with intended
Alcoholism: Clinical and Experimental Research, May 7, 2021
BackgroundObjective measurement of alcohol consumption is important for clinical care and researc... more BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self‐reported alcohol use, we conducted an individual participant data (IPD) meta‐analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self‐reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1‐step IPD meta‐analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index—BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger‐prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self‐reported alcohol use using the AUDIT‐C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT‐C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.