Browsing by Author "Mweemba, Aggrey"

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Chronic hepatitis B virus coinfection is associated with renal impairment among Zambian HIV-infected adults.
(2014-Dec-15) Mweemba, Aggrey; Zanolini, Arianna; Mulenga, Lloyd; Emge, Drew; Chi, Benjamin H.; Wandeler, Gilles; Vinikoor, Michael J.
Among 6789 HIV-infected Zambian adults screened for hepatitis B virus (HBV) coinfection, estimated glomerular filtration rate (eGFR) was 50-90 mL/minute/1.73 m(2) in 17.6% and <50 mL/minute/1.73 m(2) in 2.5%. Human immunodeficiency virus/HBV coinfection was associated with eGFR <50 mL/minute/1.73 m(2) (adjusted odds ratio, 1.96 [95% confidence interval, 1.34-2.86]), adjusted for age, sex, CD4(+) count, and World Health Organization disease stage.
Effect of baseline renal function on tenofovir-containing antiretroviral therapy outcomes in Zambia.
(2014-May) Mulenga, Lloyd; Musonda, Patrick; Mwango, Albert; Vinikoor, Michael J.; Davies, Mary-Ann; Mweemba, Aggrey; Calmy, Alexandra; Stringer, Jeffrey S.; Keiser, Olivia; Chi, Benjamin H.; Wandeler, Gilles
BACKGROUND: Although tenofovir disoproxil fumarate (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia. METHODS: We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (estimated glomerular filtration rate [eGFR], 60-89 mL/min), moderate (30-59 mL/min), or severe (<30 mL/min) according to the chronic kidney disease-epidemiology (CKD-EPI) formula. Differences in eGFR during ART were analyzed using linear mixed-effect models. The odds of developing moderate or severe eGFR decrease and mortality were assessed using logistic and competing risk regression, respectively. RESULTS: We included 62 230 adults, of which 38 716 (62.2%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF than in the non-TDF group (1.9% vs 4.0%). Among patients with no or mild renal dysfunction, those receiving TDF were more likely to develop moderate (adjusted odds ratio, 3.11; 95% confidence interval, 2.52-3.87) or severe (2.43; 1.80-3.28) eGFR decrease, although the incidence in such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen, and mortality rates were similar in both treatment groups. CONCLUSIONS: TDF use did not attenuate renal function recovery or increase the mortality rate in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa.
Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia.
(2015-Jul) Vinikoor, Michael J.; Sinkala, Edford; Mweemba, Aggrey; Zanolini, Arianna; Mulenga, Lloyd; Sikazwe, Izukanji; Fried, Micahel W.; Eron, Joseph J.; Wandeler, Gilles; Chi, Benjamin H.
BACKGROUND & AIMS: We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia. METHODS: Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunological status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. RESULTS: Among 20 308 adults in the analysis cohort, 1027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI <18, WHO clinical stage 3 or 4, CD4(+) count <200 cells/mm(3) , and tuberculosis. Among the 237 (1.2%) who were tested, HBsAg-positive patients had four times the odds (adjusted odds ratio, 4.15; 95% CI, 1.71-10.04) of significant fibrosis compared HBsAg-negatives. Both significant fibrosis (adjusted hazard ratio 1.41, 95% CI, 1.21-1.64) and cirrhosis (adjusted hazard ratio 1.57, 95% CI, 1.31-1.89) were associated with increased all-cause mortality. CONCLUSION: Liver fibrosis may be a risk factor for mortality during ART among HIV-infected individuals in Africa. APRI is an inexpensive and potentially useful test for liver fibrosis in resource-constrained settings.
Evolution of HIV-1 drug resistance after virological failure of first-line antiretroviral therapy in Lusaka, Zambia.
(2019) Hudson, Parker F.; Mulenga, Lloyd; Westfall, Andrew O.; Warrier, Ranjit; Mweemba, Aggrey; Saag, Michael S.; Stringer, Jeffrey S.; Eron, Joseph J.; Chi, Benjamin H.
BACKGROUND: HIV viral load (VL) and resistance testing are limited in sub-Saharan Africa, so individuals may have prolonged time on failing first-line antiretroviral therapy (ART). Our objective was to describe the evolution of drug resistance mutations among adults failing first-line ART in Zambia. METHODS: We analysed data from a trial of VL monitoring in Lusaka, Zambia. From 2006 to 2011, 12 randomized sites provided either routine VL monitoring (intervention) or discretionary (control) after ART initiation. Samples were collected prospectively following the same schedule in each arm but analysed retrospectively in the control group. For those with virological failure (VF; >400 copies/ml), HIV genotyping was performed retrospectively on baseline (BL) and on all subsequent specimens until censored due to study completion, withdrawal or death. RESULTS: Of 1,973 enrollees, 165 (8.4%) developed VF. 464 genotype results were available including 132 (80%) at BL, 116 (70%) at VF and 125 (76%) had at least one result between VF and censoring. Major nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations increased from 26% (BL) to 82% (VF) to 89% at last genotype (LG). M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. Among those on a failing tenofovir disoproxil fumarate (TDF)-based regimen, TDF resistance increased from 42% to 58%. CONCLUSIONS: We found substantial resistance to NRTIs and NNRTIs at VF with incremental increases after VF while still on a failing first-line ART; this resistance may compromise attainment of the UNAIDS 90-90-90 goals.