Journal Article > LetterAbstract Only
Lancet HIV. 1 October 2024; Volume 11 (Issue 10); e711-e716.; DOI:10.1016/S2352-3018(24)00173-5
Venter WDF, Gandhi M, Sokhela S, Sikwese K, Bygrave H, et al.
Lancet HIV. 1 October 2024; Volume 11 (Issue 10); e711-e716.; DOI:10.1016/S2352-3018(24)00173-5
Journal Article > ResearchFull Text
PLOS Glob Public Health. 27 March 2023; Volume 3 (Issue 3); e0001678.; DOI:10.1371/journal.pgph.0001678
Boyce RM, Ndizeye R, Ngelese H, Baguma E, Shem B, et al.
PLOS Glob Public Health. 27 March 2023; Volume 3 (Issue 3); e0001678.; DOI:10.1371/journal.pgph.0001678
Barriers continue to limit access to viral load (VL) monitoring across sub-Saharan Africa adversely impacting control of the HIV epidemic. The objective of this study was to determine whether the systems and processes required to realize the potential of rapid molecular technology are available at a prototypical lower-level (i.e., level III) health center in rural Uganda. In this open-label pilot study, participants underwent parallel VL testing at both the central laboratory (i.e., standard of care) and on-site using the GeneXpert HIV-1 assay. The primary outcome was the number of VL tests completed each clinic day. Secondary outcomes included the number of days from sample collection to receipt of result at clinic and the number of days from sample collection to patient receipt of the result. From August 2020 to July 2021, we enrolled a total of 242 participants. The median number of daily tests performed on the Xpert platform was 4, (IQR = 2–7). Time from sample collection to result was 51 days (IQR = 45–62) for samples sent to the central laboratory and 0 days (IQR = 0–0.25) for the Xpert assay conducted at the health center. However, few participants elected to receive results by one of the expedited options, which contributed to similar time-to-patient between testing approaches (89 versus 84 days, p = 0.07). Implementation of a rapid, near point-of-care VL assay at a lower-level health center in rural Uganda appears feasible, but interventions to promote rapid clinical response and influence patient preferences about result receipt require further study.
Journal Article > ResearchFull Text
PLOS One. 6 February 2015; Volume 10 (Issue 2); DOI:10.1371/journal.pone.0118191
Orikiriza P, Tibenderana B, Siedner MJ, Mueller YK, Byarugaba F, et al.
PLOS One. 6 February 2015; Volume 10 (Issue 2); DOI:10.1371/journal.pone.0118191
There are limited data on region-specific drug susceptibility of tuberculosis (TB) in Uganda. We performed resistance testing on specimens collected from treatment-naive patients with pulmonary TB in Southwestern Uganda for first and second line anti-TB drugs. We sought to provide data to guide regional recommendations for empiric TB therapy.
Journal Article > ResearchAbstract Only
AIDS Behav. 2 June 2016; Volume 21 (Issue 6); 1735-1740.; DOI:10.1007/s10461-016-1447-1
Musinguzi N, Mocello AR, Boum Y II, Hunt PW, Martin JN, et al.
AIDS Behav. 2 June 2016; Volume 21 (Issue 6); 1735-1740.; DOI:10.1007/s10461-016-1447-1
Little is known about associations between viral suppression, adherence, and duration of prior viral suppression in sub-Saharan Africa. Study participants were from the UARTO study in Mbarara, Uganda. We fit regression models to characterize relationships between average adherence, treatment interruptions, and rebound viremia (>400 copies/mL) following a previously undetectable result. Our goal was to understand the impact of prior viral suppression on these relationships. 396 participants contributed 2864 quarterly visits. Restricted to periods with average adherence <50%, each 10% increase in adherence reduced the odds of rebound viremia by 74% [adjusted odds ratio (AOR) = 0.26, P = 0.002] and 29 % (AOR = 0.71, P = 0.057) during the first 12 months of suppression and beyond 12 months respectively, interaction term P = 0.018. Among periods with adherence ≥50%, the risk of rebound viremia decreased with increasing adherence during the first 12 months of viral suppression (AOR = 0.73 for each 10 % increase, P = 0.001), but not thereafter (AOR = 1.09, P = 0.67), interaction term P = 0.027. In contrast, 72-h interruptions, were associated with increased rebound viremia during the first 12 months (AOR = 1.30, P = 0.009) and after (AOR = 1.39, P = 0.005), interaction term P = 0.69. Completing 12 months of viral suppression decreases the impact of average adherence, but not prolonged treatment interruptions, on risk of rebound viremia.
Journal Article > ResearchFull Text
J Acquir Immune Defic Syndr. 16 January 2018; Volume 77 (Issue 5); DOI:10.1097/QAI.0000000000001629
Castillo-Mancilla JR, Morrow M, Boum Y II, Byakwaga H, Haberer JE, et al.
J Acquir Immune Defic Syndr. 16 January 2018; Volume 77 (Issue 5); DOI:10.1097/QAI.0000000000001629
Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays.
Journal Article > ResearchFull Text
SSM Ment Health. 1 December 2021; Volume 1; 100034.; DOI:10.1016/j.ssmmh.2021.100034
Bebell LM, Kembabazi A, Musinguzi N, Martin JN, Hunt PW, et al.
SSM Ment Health. 1 December 2021; Volume 1; 100034.; DOI:10.1016/j.ssmmh.2021.100034
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×time product 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=0.03; 95% confidence interval [CI], 0.02 to 0.04) and negatively associated with ART duration >6 months (b =- 0.16; 95% CI,- 0.19 to -0.13). The estimated product term coefficient was negative and statistically significant (P = 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.
Journal Article > ResearchFull Text
AIDS. 8 January 2014; Volume 28 (Issue 8); 1221-6.; DOI:10.1097/QAD.0000000000000188
Venkataramani AS, Thirumurthy H, Haberer JE, Boum Y II, Siedner MJ, et al.
AIDS. 8 January 2014; Volume 28 (Issue 8); 1221-6.; DOI:10.1097/QAD.0000000000000188
OBJECTIVE
To determine whether earlier initiation of antiretroviral therapy (ART) is associated with better economic outcomes.
DESIGN
Prospective cohort study of HIV-positive patients on ART in rural Uganda.
METHODS
Patients initiating ART at a regional referral clinic in Uganda were enrolled in the Uganda AIDS Rural Treatment Outcomes study starting in 2005. Data on labor force participation and asset ownership were collected on a yearly basis, and CD4 cell counts were collected at pre-ART baseline. We fitted multivariable regression models to assess whether economic outcomes at baseline and in the 6 years following ART initiation varied by baseline CD4 cell count.
RESULTS
Five hundred and five individuals, followed up to 6 years, formed the estimation sample. Participants initiating ART at CD4 cell count at least 200 cells/μl were 13 percentage points more likely to be working at baseline (P < 0.01, 95% confidence interval 0.06-0.21) than those initiating below this threshold. Those in the latter group achieved similar labor force participation rates within 1 year of initiating ART (P < 0.01 on the time indicators). Both groups had similar asset scores at baseline and demonstrated similar increases in asset scores over the 6 years of follow-up.
CONCLUSION
ART helps participants initiating therapy at CD4 cell count below 200 cells/μl rejoin the labor force, though the findings for participants initiating with higher CD4 cell counts suggests that pretreatment declines in labor supply may be prevented altogether with earlier therapy. Baseline similarities in asset scores for those with early and advanced disease suggest that mechanisms other than morbidity may help drive the relationship between HIV infection and economic outcomes.
To determine whether earlier initiation of antiretroviral therapy (ART) is associated with better economic outcomes.
DESIGN
Prospective cohort study of HIV-positive patients on ART in rural Uganda.
METHODS
Patients initiating ART at a regional referral clinic in Uganda were enrolled in the Uganda AIDS Rural Treatment Outcomes study starting in 2005. Data on labor force participation and asset ownership were collected on a yearly basis, and CD4 cell counts were collected at pre-ART baseline. We fitted multivariable regression models to assess whether economic outcomes at baseline and in the 6 years following ART initiation varied by baseline CD4 cell count.
RESULTS
Five hundred and five individuals, followed up to 6 years, formed the estimation sample. Participants initiating ART at CD4 cell count at least 200 cells/μl were 13 percentage points more likely to be working at baseline (P < 0.01, 95% confidence interval 0.06-0.21) than those initiating below this threshold. Those in the latter group achieved similar labor force participation rates within 1 year of initiating ART (P < 0.01 on the time indicators). Both groups had similar asset scores at baseline and demonstrated similar increases in asset scores over the 6 years of follow-up.
CONCLUSION
ART helps participants initiating therapy at CD4 cell count below 200 cells/μl rejoin the labor force, though the findings for participants initiating with higher CD4 cell counts suggests that pretreatment declines in labor supply may be prevented altogether with earlier therapy. Baseline similarities in asset scores for those with early and advanced disease suggest that mechanisms other than morbidity may help drive the relationship between HIV infection and economic outcomes.
Journal Article > ResearchFull Text
PLOS One. 13 April 2017; Volume 12 (Issue 4); e0175456.; DOI:10.1371/journal.pone.0175456
Bebell LM, Ngonzi J, Bazira J, Fajardo Y, Boatin AA, et al.
PLOS One. 13 April 2017; Volume 12 (Issue 4); e0175456.; DOI:10.1371/journal.pone.0175456
INTRODUCTION
Puerperal sepsis causes 10% of maternal deaths in Africa, but prospective studies on incidence, microbiology and antimicrobial resistance are lacking.
METHODS
We performed a prospective cohort study of 4,231 Ugandan women presenting to a regional referral hospital for delivery or postpartum care, measured vital signs after delivery, performed structured physical exam, symptom questionnaire, and microbiologic evaluation of febrile and hypothermic women. Malaria rapid diagnostic testing, blood and urine cultures were performed aseptically and processed at Epicentre Mbarara Research Centre. Antimicrobial susceptibility and breakpoints were determined using disk diffusion per EUCAST standards. Hospital diagnoses, treatments and outcomes were abstracted from patient charts.
RESULTS
Mean age was 25 years, 12% were HIV-infected, and 50% had cesarean deliveries. Approximately 5% (205/4176) with ≥1 temperature measurement recorded developed postpartum fever or hypothermia; blood and urine samples were collected from 174 (85%), and 17 others were evaluated clinically. Eighty-four (48%) had at least one confirmed source of infection: 39% (76/193) clinical postpartum endometritis, 14% (25/174) urinary tract infection (UTI), 3% (5/174) bloodstream infection. Another 3% (5/174) had malaria. Overall, 30/174 (17%) had positive blood or urine cultures, and Acinetobacter species were the most common bacteria isolated. Of 25 Gram-negatives isolated, 20 (80%) were multidrug-resistant and cefepime non-susceptible.
CONCLUSIONS
For women in rural Uganda with postpartum fever, we found a high rate of antibiotic resistance among cultured urinary and bloodstream infections, including cephalosporin-resistant Acinetobacter species. Increasing availability of microbiology testing to inform appropriate antibiotic use, development of antimicrobial stewardship programs, and strengthening infection control practices should be high priorities.
Puerperal sepsis causes 10% of maternal deaths in Africa, but prospective studies on incidence, microbiology and antimicrobial resistance are lacking.
METHODS
We performed a prospective cohort study of 4,231 Ugandan women presenting to a regional referral hospital for delivery or postpartum care, measured vital signs after delivery, performed structured physical exam, symptom questionnaire, and microbiologic evaluation of febrile and hypothermic women. Malaria rapid diagnostic testing, blood and urine cultures were performed aseptically and processed at Epicentre Mbarara Research Centre. Antimicrobial susceptibility and breakpoints were determined using disk diffusion per EUCAST standards. Hospital diagnoses, treatments and outcomes were abstracted from patient charts.
RESULTS
Mean age was 25 years, 12% were HIV-infected, and 50% had cesarean deliveries. Approximately 5% (205/4176) with ≥1 temperature measurement recorded developed postpartum fever or hypothermia; blood and urine samples were collected from 174 (85%), and 17 others were evaluated clinically. Eighty-four (48%) had at least one confirmed source of infection: 39% (76/193) clinical postpartum endometritis, 14% (25/174) urinary tract infection (UTI), 3% (5/174) bloodstream infection. Another 3% (5/174) had malaria. Overall, 30/174 (17%) had positive blood or urine cultures, and Acinetobacter species were the most common bacteria isolated. Of 25 Gram-negatives isolated, 20 (80%) were multidrug-resistant and cefepime non-susceptible.
CONCLUSIONS
For women in rural Uganda with postpartum fever, we found a high rate of antibiotic resistance among cultured urinary and bloodstream infections, including cephalosporin-resistant Acinetobacter species. Increasing availability of microbiology testing to inform appropriate antibiotic use, development of antimicrobial stewardship programs, and strengthening infection control practices should be high priorities.
Journal Article > ResearchFull Text
Ann Glob Health. 12 March 2015; Volume 81 (Issue 1); 207.; DOI:10.1016/j.aogh.2015.02.977
Kim JH, Hemphill LC, Boum Y II, Bangsberg DR, Siedner MJ
Ann Glob Health. 12 March 2015; Volume 81 (Issue 1); 207.; DOI:10.1016/j.aogh.2015.02.977
BACKGROUND
Non-communicable diseases (NCDs) account for the majority of adult deaths worldwide, and 80% of these deaths occur in
low and middle-income countries (LMICs). The burden of NCDs in LMICs is predicted to grow with improvements in sanitation and infectious disease control, and will be altered by local diet, smoking rates, and HIV co-infection. There is a critical need to identify and implement low-cost, well-validated diagnostic tests to elucidate the epidemiology of NCDs, and enable diagnostic monitoring and ther- apeutic interventions. Moreover, tests that enable non-healthcare professionals to lead care provision will augment the scalability of this strategy. We recently completed implementation and evaluation of a bundle of point-of-care, low-cost diagnostics for NCD measurement in rural Uganda.
METHODS
We performed a cross-sectional cohort study in rural, southwestern Uganda of HIV-infected persons on antiretroviral therapy at the Mbarara Regional Referral Hospital and a control group of HIV-uninfected persons from the clinic catchment area. Three non-healthcare professional Ugandan staff completed a two- week intensive course to perform a series of point-of-care cardiovas- cular assessments, including portable electrocardiogram (EKG), ankle-brachial index (ABI), hemoglobin A1c testing (HbA1c), auto- mated blood pressure, and anthropometric measurements. An American medical student was trained through the University of Wisconsin Atherosclerosis Imaging Research Program to perform measurement of carotid intima-media thickness (CIMT). We assessed the quality and feasibility of each measurement by: 1) proportion of valid hemoglobin A1c results; 2) proportion of interpretable carotid ultrasound images as graded by a board-certified vascular cardiologist using the University of Wisconsin CIMT image quality assessment scale; and 3) correlation between brachial blood pressure measure- ments and automated systolic blood pressure measurements. The study received ethics approval from the Mbarara University of Science & Technology and Partners Healthcare. All participants provided written informed consent.
FINDINGS
105 HIV-infected and 90 HIV-uninfected individuals were enrolled in the study. None of the HbA1c tests were invalid (0/ 195). Of the 96 CIMT images reviewed, 86 (90%) were found to be of adequate quality, and 10 (10.4%) were not suitable for measure- ment. The right and left brachial blood pressure measurements had coefficients of determination of 0.79 and 0.72, respectively, with the automated systolic blood pressure measurements. Based on an esti- mate patient volume of 1,000 patients per year and measurement for 3 years, the cost for this array of tests, including capital equipment, would be approximately $28 per patient.
INTERPRETATION
Low-cost, portable, and well-validated point-of-care tests can be implemented by non-medical professionals in LMICs. Implementation evaluations should be pursued to assess the large- scale feasibility, scalability, and impact of this strategy.
Non-communicable diseases (NCDs) account for the majority of adult deaths worldwide, and 80% of these deaths occur in
low and middle-income countries (LMICs). The burden of NCDs in LMICs is predicted to grow with improvements in sanitation and infectious disease control, and will be altered by local diet, smoking rates, and HIV co-infection. There is a critical need to identify and implement low-cost, well-validated diagnostic tests to elucidate the epidemiology of NCDs, and enable diagnostic monitoring and ther- apeutic interventions. Moreover, tests that enable non-healthcare professionals to lead care provision will augment the scalability of this strategy. We recently completed implementation and evaluation of a bundle of point-of-care, low-cost diagnostics for NCD measurement in rural Uganda.
METHODS
We performed a cross-sectional cohort study in rural, southwestern Uganda of HIV-infected persons on antiretroviral therapy at the Mbarara Regional Referral Hospital and a control group of HIV-uninfected persons from the clinic catchment area. Three non-healthcare professional Ugandan staff completed a two- week intensive course to perform a series of point-of-care cardiovas- cular assessments, including portable electrocardiogram (EKG), ankle-brachial index (ABI), hemoglobin A1c testing (HbA1c), auto- mated blood pressure, and anthropometric measurements. An American medical student was trained through the University of Wisconsin Atherosclerosis Imaging Research Program to perform measurement of carotid intima-media thickness (CIMT). We assessed the quality and feasibility of each measurement by: 1) proportion of valid hemoglobin A1c results; 2) proportion of interpretable carotid ultrasound images as graded by a board-certified vascular cardiologist using the University of Wisconsin CIMT image quality assessment scale; and 3) correlation between brachial blood pressure measure- ments and automated systolic blood pressure measurements. The study received ethics approval from the Mbarara University of Science & Technology and Partners Healthcare. All participants provided written informed consent.
FINDINGS
105 HIV-infected and 90 HIV-uninfected individuals were enrolled in the study. None of the HbA1c tests were invalid (0/ 195). Of the 96 CIMT images reviewed, 86 (90%) were found to be of adequate quality, and 10 (10.4%) were not suitable for measure- ment. The right and left brachial blood pressure measurements had coefficients of determination of 0.79 and 0.72, respectively, with the automated systolic blood pressure measurements. Based on an esti- mate patient volume of 1,000 patients per year and measurement for 3 years, the cost for this array of tests, including capital equipment, would be approximately $28 per patient.
INTERPRETATION
Low-cost, portable, and well-validated point-of-care tests can be implemented by non-medical professionals in LMICs. Implementation evaluations should be pursued to assess the large- scale feasibility, scalability, and impact of this strategy.
Journal Article > ResearchFull Text
Malar J. 23 February 2022; Volume 21 (Issue 1); 63.; DOI:10.1186/s12936-022-04086-w
Boyce RM, Muhindo E, Baguma E, Muhindo R, Shem B, et al.
Malar J. 23 February 2022; Volume 21 (Issue 1); 63.; DOI:10.1186/s12936-022-04086-w
BACKGROUND
Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed.
METHODS
The pilot was a randomized, placebo-controlled pilot study of permethrin-treated baby wraps-known locally as lesus-in children 6-18 months of age at a single site in rural western Uganda. Fifty mother-infant pairs were assigned to permethrin-treated or untreated lesus in a 1:1 allocation. Participants and clinical staff were blinded to group assignments through use of sham treatment and re-treatment of lesus. Participants attended scheduled clinic visits every 2 weeks for a total 12 weeks. The primary outcome of interest was the safety of the intervention, assessed as changes in the frequency of use, rates of discontinuation, and incidence of adverse events, such as skin rash. Secondary outcomes included acceptability and feasibility of the intervention as measured through participant satisfaction and completion of study activities, respectively.
RESULTS
Overall, rates of retention and participation were relatively high with 86.0% (43 of 50) of participants completing all scheduled visits, including 18 (75.0%) and 25 (96.2%) in the intervention and control arms respectively. By the conclusion of the 12-week follow-up period, one adverse event (0.35 events per 100 person-weeks, one-sided 95% CI 0.0-1.65) was reported. Satisfaction with the lesu was high in both groups. In each study arm, there were five incident RDT positive results, but the only PCR-positive results were observed in the control group (n = 2).
CONCLUSIONS
Permethrin-treated baby wraps were well-tolerated and broadly acceptable. Adverse events were infrequent and mild. These findings support future trials seeking to determine the efficacy of treated wraps to prevent P. falciparum malaria infection in young children as a complementary tool to existing household-based interventions.
Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed.
METHODS
The pilot was a randomized, placebo-controlled pilot study of permethrin-treated baby wraps-known locally as lesus-in children 6-18 months of age at a single site in rural western Uganda. Fifty mother-infant pairs were assigned to permethrin-treated or untreated lesus in a 1:1 allocation. Participants and clinical staff were blinded to group assignments through use of sham treatment and re-treatment of lesus. Participants attended scheduled clinic visits every 2 weeks for a total 12 weeks. The primary outcome of interest was the safety of the intervention, assessed as changes in the frequency of use, rates of discontinuation, and incidence of adverse events, such as skin rash. Secondary outcomes included acceptability and feasibility of the intervention as measured through participant satisfaction and completion of study activities, respectively.
RESULTS
Overall, rates of retention and participation were relatively high with 86.0% (43 of 50) of participants completing all scheduled visits, including 18 (75.0%) and 25 (96.2%) in the intervention and control arms respectively. By the conclusion of the 12-week follow-up period, one adverse event (0.35 events per 100 person-weeks, one-sided 95% CI 0.0-1.65) was reported. Satisfaction with the lesu was high in both groups. In each study arm, there were five incident RDT positive results, but the only PCR-positive results were observed in the control group (n = 2).
CONCLUSIONS
Permethrin-treated baby wraps were well-tolerated and broadly acceptable. Adverse events were infrequent and mild. These findings support future trials seeking to determine the efficacy of treated wraps to prevent P. falciparum malaria infection in young children as a complementary tool to existing household-based interventions.