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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.(2025-Feb-05) Skrivankova VW; Huwa J; Muula G; Chiwaya GD; Banda E; Buleya S; Chihota B; Chintedza J; Bolton C; Tweya H; Kalua T; Hossmann S; Kouyos R; Wandeler G; Egger M; Lessells RJBACKGROUND: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year. METHODS: We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL. RESULTS: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. CONCLUSIONS: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT04612452).Item Association of cardiovascular disease risk with liver steatosis and fibrosis in people with HIV in low- and middle-income countries.(2025-Jan-01) Kuniholm MH; Murenzi G; Shumbusho F; Brazier E; Plaisy MK; Mensah E; Wandeler G; Riebensahm C; Chihota BV; Samala N; Diero L; Semeere AS; Chanyachukul T; Borse R; Nguyen DTH; Perazzo H; Lopez-Iniguez A; Castilho JL; Maruri F; Jaquet AOBJECTIVE: The aim of this study was to understand the relationship between cardiovascular disease (CVD) risk and liver steatosis and fibrosis among people with HIV (PLWH) at least 40 years of age on antiretroviral therapy (ART) in low and middle-income countries (LMIC). DESIGN: We used cross-sectional behavioral and clinical data collected during study enrollment visits in 2020-2022 for the Sentinel Research Network of International epidemiology Databases to Evaluate AIDS (SRN of IeDEA). METHODS: Ten-year CVD risk was calculated using 2019 WHO nonlaboratory and laboratory models. Transient elastography was used to assess liver disease. Presence of steatosis and significant fibrosis were defined by controlled attenuation parameter (CAP) at least 248 dB/m and liver stiffness measurement (LSM) at least 7.1 kPa, respectively. Participants with viral hepatitis, hazardous alcohol consumption, and unsuppressed HIV viral load were excluded from the analysis. Logistic regression was used to estimate odds ratios, adjusting for study site, CD4 + T cell count, stavudine and didanosine exposure, and in models stratified by sex and geographic region. RESULTS: There were 1750 participants from nine LMIC. Median CVD risk was 3% for both nonlaboratory and laboratory-based models. Adjusted odds ratios (ORs) for steatosis and significant fibrosis associated with laboratory CVD risk (≥10 vs. <5%) were OR = 1.83 [95% confidence interval (95% CI) = 1.21-2.76; P = 0.004] and OR = 1.62 (95% CI = 0.85-3.07; P = 0.14), respectively. Associations of CVD risk with steatosis were stronger in men and among participants at study sites outside Africa. CONCLUSION: Higher CVD risk was associated with steatosis but not with significant fibrosis in PWH in our LMIC cohort.Item Effect of baseline renal function on tenofovir-containing antiretroviral therapy outcomes in Zambia.(2014-May) Mulenga L; Musonda P; Mwango A; Vinikoor MJ; Davies MA; Mweemba A; Calmy A; Stringer JS; Keiser O; Chi BH; Wandeler GBACKGROUND: 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.Item Chronic hepatitis B virus coinfection is associated with renal impairment among Zambian HIV-infected adults.(2014-Dec-15) Mweemba A; Zanolini A; Mulenga L; Emge D; Chi BH; Wandeler G; Vinikoor MJAmong 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.Item Cohort profile: Noncommunicable diseases and ideal cardiovascular health among people living with and without HIV in Zambia and Zimbabwe (NCDzz cohort).(2025-Feb-07) Chihota BV; Mandiriri A; Muula G; Banda E; Shamu T; Bolton-Moore C; Chimbetete C; Bosomprah S; Wandeler GPURPOSE: The NCDzz study is a prospective cohort of people living with and without HIV attending primary care clinics in Zambia and Zimbabwe and was established in 2019 to understand the intersection between noncommunicable diseases (NCDs) and HIV in Southern Africa. Here, we describe the study design and population and evaluate their ideal cardiovascular health (ICVH) using the Life's Simple 7 (LS7) score according to the American Heart Association. PARTICIPANTS: Antiretroviral therapy-naïve people living with HIV (PLWH) and people living without HIV (PLWOH) 30 years or older were recruited from three primary care clinics in Lusaka and Harare, and underwent comprehensive clinical, laboratory and behavioural assessments. All study measurements are repeated during yearly follow-up visits. PLWOH were recruited from the same neighbourhoods and had similar socioeconomic conditions as PLWH. FINDINGS TO DATE: Between August 2019 and March 2023, we included 1100 adults, of whom 618 (56%) were females and 539 (49%) were PLWH. The median age at enrolment was 39 years (IQR 34-46 years). Among 1013 participants (92%) with complete data, the median LS7 score was 11/14 (IQR 10-12). Overall, 60% of participants met the criteria of ICVH metrics (5-7 ideal components) and among individual components of the LS7, more females had poor body mass index (BMI) than males, regardless of HIV status (27% vs 3%, p<0.001). Our data show no apparent difference in cardiovascular health determinants between men and women, but high BMI in women and overall high hypertension prevalence need detailed investigation. Untreated HIV (OR: 1.36 (IQR 1.05-1.78)) and being a Zambian participant (OR: 1.81 (IQR 1.31-2.51)) were associated with having ICVH metrics, whereas age older than 50 years (OR: 0.46 (IQR 0.32-0.65)) was associated with not having ICVH metrics. FUTURE PLANS: Our study will be regularly updated with upcoming analyses using prospective data including a focus on arterial hypertension and vascular function. We plan to enrich the work through conducting in-depth assessments on the determinants of cardiovascular, liver and kidney end-organ disease outcomes yearly. Additionally, we seek to pilot NCD interventions using novel methodologies like the trials within cohorts. Beyond the initial funding support, we aim to collect at minimum yearly data for an additional 5-year period.Item Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia.(2015-Jul) Vinikoor MJ; Sinkala E; Mweemba A; Zanolini A; Mulenga L; Sikazwe I; Fried MW; Eron JJ; Wandeler G; Chi BHBACKGROUND & 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.Item Response to 'Is AST-to-platelet ratio index a reliable tool in HIV patients in Africa?'.(2015-Aug) Vinikoor MJ; Sinkala E; Wandeler G; Chi BHItem Implementation of routine screening for chronic hepatitis B virus co-infection by HIV clinics in Lusaka, Zambia.(2015-Oct) Vinikoor MJ; Musukuma K; Munamunungu V; Masaninga M; Sikazwe I; Chi BH; Wandeler GItem Hepatitis B viral load in dried blood spots: A validation study in Zambia.(2015-Nov) Vinikoor MJ; Zürcher S; Musukuma K; Kachuwaire O; Rauch A; Chi BH; Gorgievski M; Zwahlen M; Wandeler GBACKGROUND: Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons. OBJECTIVES: To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples. STUDY DESIGN: Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for HBV genotype by direct sequencing. We used Bland-Altman analysis to compare VLs between sample types and by genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL. RESULTS: Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98logIU/ml (interquartile range, 2.04-5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59logIU/ml lower than plasma with 95% limits of agreement of -2.40 to -0.83log IU/ml. At a plasma VL ≥2,000IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5-6.6). At plasma VL ≥20,000IU/ml this probability reduced to 0.2% (95% CI: 0.03-1.7). CONCLUSIONS: In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL ≥2,000IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing and care in SSA settings.Item Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis.(2015-Jul) Haas AD; Keiser O; Balestre E; Brown S; Bissagnene E; Chimbetete C; Dabis F; Davies MA; Hoffmann CJ; Oyaro P; Parkes-Ratanshi R; Reynolds SJ; Sikazwe I; Wools-Kaloustian K; Zannou DM; Wandeler G; Egger MBACKGROUND: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa. METHODS: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics. FINDINGS: Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL). INTERPRETATION: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing. FUNDING: National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.