Browsing by Author "Mulenga L"

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A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia.
(2008-Oct-01) Cantrell RA; Sinkala M; Megazinni K; Lawson-Marriott S; Washington S; Chi BH; Tambatamba-Chapula B; Levy J; Stringer EM; Mulenga L; Stringer JS; Centre for Infectious Disease Research in Zambia, Plot 1275 Lubutu Road, Lusaka, Zambia. cantrell@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The provision of food supplementation to food-insecure patients initiating antiretroviral therapy (ART) may improve adherence to medications. METHODS: A home-based adherence support program at 8 government clinics assessed patients for food insecurity. Four clinics provided food supplementation, and 4 acted as controls. The analysis compared adherence (assessed by medication possession ratio), CD4, and weight gain outcomes among food-insecure patients enrolled at the food clinics with those enrolled at the control clinics. RESULTS: Between May 1, 2004, and March 31, 2005, 636 food- insecure adults were enrolled. Food supplementation was associated with better adherence to therapy. Two hundred fifty-eight of 366 (70%) patients in the food group achieved a medication possession ratio of 95% or greater versus 79 of 166 (48%) among controls (relative risk = 1.5; 95% confidence interval: 1.2 to 1.8). This finding was unchanged after adjustment for sex, age, baseline CD4 count, baseline World Health Organization stage, and baseline hemoglobin. We did not observe a significant effect of food supplementation on weight gain or CD4 cell response. CONCLUSIONS: This analysis suggests that providing food to food-insecure patients initiating ART is feasible and may improve adherence to medication. A large randomized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy.
Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique.
(2016-Mar) Wandeler G; Mulenga L; Hobbins M; Joao C; Sinkala E; Hector J; Aly M; Chi BH; Egger M; Vinikoor MJ; Department of Infectious Diseases, Bern University Hospital; Institute of Social and Preventive Medicine, University of Bern, Switzerland; Department of Infectious Diseases, University of Dakar, Senegal.; School of Medicine, Department of Medicine, University of Zambia, Lusaka; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Alabama at Birmingham.; School of Medicine, Department of Medicine, University of Zambia, Lusaka; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; Nucleo de Investigação Operacional, Pemba , Mozambique.; SolidarMed , Ancuabe, Mozambique, Lucerne , Switzerland.; Institute of Social and Preventive Medicine, University of Bern, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa.; Department of Obstetrics and Gynecology , University of North Carolina at Chapel Hill.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.
Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia.
(2016-Nov) Vinikoor MJ; Mulenga L; Siyunda A; Musukuma K; Chilengi R; Moore CB; Chi BH; Davies MA; Egger M; Wandeler G; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Medicine, University of Zambia, Lusaka, Zambia.; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Medicine, University of Zambia, Lusaka, Zambia. mjv3@uab.edu.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. mjv3@uab.edu.; University Teaching Hospital, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. mjv3@uab.edu.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Infectious Diseases, University of Dakar, Dakar, Senegal.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To describe liver disease epidemiology among HIV-infected individuals in Zambia. METHODS: We recruited HIV-infected adults (≥18 years) at antiretroviral therapy initiation at two facilities in Lusaka. Using vibration controlled transient elastography, we assessed liver stiffness, a surrogate for fibrosis/cirrhosis, and analysed liver stiffness measurements (LSM) according to established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for cirrhosis). All participants underwent standardised screening for potential causes of liver disease including chronic hepatitis B (HBV) and C virus co-infection, herbal medicine, and alcohol use. We used multivariable logistic regression to identify factors associated with elevated liver stiffness. RESULTS: Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53% female). HBV co-infection (12%) and alcohol use disorders (41%) were common and hepatitis C virus co-infection (<1%) was rare. According to LSM, 75 (12%) had significant fibrosis and 13 (2%) had cirrhosis. In multivariable analysis, HBV co-infection as well as male sex, increased age and WHO clinical stage 3 or 4 were independently associated with LSM >7.0 kPa (all P < 0.05). HBV co-infection was the only independent risk factor for LSM >11.0 kPa. Among HIV-HBV patients, those with elevated ALT and HBV viral load were more likely to have significant liver fibrosis than patients with normal markers of HBV activity. CONCLUSIONS: HBV co-infection was the most important risk factor for liver fibrosis and cirrhosis and should be diagnosed early in HIV care to optimise treatment outcomes.
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 MJ; Department of Medicine, University of Zambia University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill.; Institute of Social and Preventive Medicine, University of Bern Department of Infectious Diseases, University Hospital Bern, Switzerland.; Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill Centre for Infectious Disease Research in Zambia, Lusaka.; Department of Medicine, University of Zambia University Teaching Hospital, Lusaka, Zambia Centre for Infectious Disease Research in Zambia, Lusaka.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Community-based follow-up for late patients enrolled in a district-wide programme for antiretroviral therapy in Lusaka, Zambia.
(2008-Mar) Krebs DW; Chi BH; Mulenga Y; Morris M; Cantrell RA; Mulenga L; Levy J; Sinkala M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. dankrebs@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Timely adherence to clinical and pharmacy appointments is well correlated with favourable patient outcomes among HIV-infected individuals on antiretroviral therapy. To date, however, there is little work exploring reasons behind missed visits or evaluating programmatic strategies to recall patients. For this study we implemented community-based follow-up of late patients as part of a large-scale programme for HIV care and treatment in Lusaka, Zambia. Through a network of local home-based care organizations, we attempted home visits to recall patients using locator information provided at time of enrolment. Between May and September 2005, home-based caregivers were dispatched to trace 1,343 patients with missed appointments. Of these, 554 (41%) were untraceable because the provided address was invalid, the patient had moved or no one was at the home. Of the remaining 789, 359 (46%) were reported to have died. Only 430 (54% of those traced, 32% overall) were contacted directly and encouraged to return for care. The likelihood of patient return was higher among traced patients in crude analysis (relative risk [RR] = 2.5; 95%CI = 1.9-3.2) and in multivariable analysis controlling for baseline body mass index, sex and CD4 + count < or = 50/microL (adjusted RR = 2.3; 95%CI = 1.7-3.2). However, the process was inefficient: one late patient returned for every 18 home visits that were made. Reasons for missed visits were provided in 271 of 430 (63%) of the patients who were successfully traced. Common reasons included feeling too sick to come to the clinic, travelling away from home and being too busy. Despite the availability of free ART in Lusaka, patients face significant barriers to attending scheduled clinical visits. Cost-effective and feasible strategies are urgently needed to improve timely patient follow-up.
Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia.
(2010-Aug-24) Koethe JR; Limbada MI; Giganti MJ; Nyirenda CK; Mulenga L; Wester CW; Chi BH; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To evaluate the relationship between early CD4(+) lymphocyte recovery on antiretroviral therapy (ART) and subsequent survival among low body mass index (BMI) HIV-1-infected adults. DESIGN: Retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: We evaluated ART-treated adults enrolled in care for more than 6 months. We stratified this study population according to World Health Organization (WHO) malnutrition criteria: normal (BMI >or=18.5 kg/m(2)), mild (17.00-18.49), moderate (16.00-16.99), and severe (<16.0). We used Cox proportional hazards regression to estimate the subsequent risk of death associated with absolute CD4(+) cell count change over the first 6 months on ART. To account for effect modification associated with baseline CD4(+) cell count, a weighted summary measure was calculated. RESULTS: From May 2004 to February 2009, 56,612 patients initiated ART at Lusaka district clinics; of these, 33 097 (58%) were included in this analysis. The median change in 0-6 month CD4(+) cell count in each baseline BMI strata varied from 127 to 131 cells/microl. There was a statistically significant, inverse association between baseline BMI and the post 6-month hazard for mortality only among those patients with less than 100 cells/microl increase in the first 6 months of ART. A CD4(+) cell count increase of at least 100 cells/microl over the first 6 months of ART was not associated with a higher hazard for mortality, regardless of baseline BMI. CONCLUSIONS: Low baseline BMI and attenuated CD4(+) cell count response at 6 months had a compounding, negative impact on post 6-month survival. Specific guidelines for monitoring ART response using immunologic criteria may be warranted for low BMI patients.
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 G; Centre for Infectious Disease Research in Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Effectiveness of generic and proprietary first-line anti-retroviral regimens in a primary health care setting in Lusaka, Zambia: a cohort study.
(2012-Apr) Stringer JS; Mwango AJ; Giganti MJ; Mulenga L; Levy JW; Stringer EM; Mulenga P; Saag MS; Musonda P; Williams FB; Reid SE; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. stringer@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Although generic anti-retroviral drugs are in common use throughout the developing world, studies comparing their clinical effectiveness with that of proprietary formulations are lacking. METHODS: We analysed observational data from a large cohort of adults on anti-retroviral therapy (ART) to assess potential differences between generic and proprietary zidovudine (ZDV) formulations in post-90-day mortality, 'programme failure' (a composite of death, follow-up losses and withdrawals) and other clinical outcomes. We accounted for drug exposure in three ways: an 'initial dispensation' approach that categorized patients according to the first prescription; 'time-varying' approach that attributed an outcome to the formulation taken at the time of event; and 'predominant exposure' approach that considered only those with >75% exposure to either brand or generic ZDV. Proprietary formulations were used as the reference group in all adjusted Cox proportional hazard regressions. RESULTS: Among 14 736 patients eligible for analysis, 7277 (49%) initiated a generic formulation of ZDV and 7459 (51%) initiated a proprietary formulation. When categorized according to initial dispensation, no difference in post-90-day mortality was observed between the two groups [adjusted hazard ratio (AHR): 0.93, 95% confidence interval (CI): 0.77-1.12]. Similar findings were noted when drug formulation was treated as a time-varying exposure (AHR: 1.15, 95% CI: 0.89-1.48) when analysis was limited to those with a predominant exposure to one formulation or the other (AHR: 0.59, 95% CI: 0.24-1.49). Results were consistent across all approaches when programme failure was considered as an outcome. No longitudinal differences were detected between formulations for CD4 response, weight change and haemoglobin concentration. Generic ZDV formulations were associated with slight decreases in single-drug substitution. CONCLUSIONS: In this large programmatic cohort of adults starting ZDV-based first-line therapy, clinical outcomes appeared similar among patients on generic or proprietary formulations. These findings support continued use of generic anti-retroviral drug formulations in resource-constrained settings.
Effects of implementing universal and rapid HIV treatment on initiation of antiretroviral therapy and retention in care in Zambia: a natural experiment using regression discontinuity.
(2021-Dec) Mody A; Sikazwe I; Namwase AS; Wa Mwanza M; Savory T; Mwila A; Mulenga L; Herce ME; Mweebo K; Somwe P; Eshun-Wilson I; Sikombe K; Beres LK; Pry J; Holmes CB; Bolton-Moore C; Geng EH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Department of Medicine, Georgetown University, Washington, DC, USA.; Zambian Ministry of Health, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA.; Center for Disease Control, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Infectious Diseases, University of Alabama, Birmingham, AL, USA.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA. Electronic address: aaloke.mody@wustl.edu.; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Universal testing and treatment (UTT) for all people living with HIV has only been assessed under experimental conditions in cluster-randomised trials. The public health effectiveness of UTT policies on the HIV care cascade under real-world conditions is not known. We assessed the real-world effectiveness of universal HIV treatment policies that were implemented in Zambia on Jan 1, 2017. METHODS: We used data from Zambia's routine electronic health record system to analyse antiretroviral therapy (ART)-naive adults who newly enrolled in HIV care up to 1 year before and after the implementation of universal treatment (ie, Jan 1, 2016, to Jan 1, 2018) at 117 clinics supported by the Centre for Infectious Disease Research in Zambia. We used a regression discontinuity design to estimate the effects of implementing UTT on same-day ART initiation, ART initiation within 1 month, and retention on ART at 12 months (defined as clinic attendance 9-15 months after enrolment and at least 6 months on ART), under the assumption that patients presenting immediately before and after UTT implementation were balanced on both measured and unmeasured characteristics. We did an instrumental variable analysis to estimate the effect of same-day ART initiation under routine conditions on 12-month retention on ART. FINDINGS: 65 673 newly enrolled patients with HIV (40 858 [62·2%] female, median age 32 years [IQR 26-39], median CD4 count 287 cells per μL [IQR 147-466]) were eligible for inclusion in the analyses; 31 145 enrolled before implementation of UTT, and 34 528 enrolled after UTT. Implementation of universal treatment increased same-day ART initiation from 41·7% to 74·8% (risk difference [RD] 33·1%, 95% CI 30·5-35·7), ART initiation by 1 month from 69·6% to 87·0% (RD 17·4%, 15·5-19·3), and 12-month retention on ART from 56·2% to 63·3% (RD 7·1%, 4·3-9·9). ART initiation rates became more uniform across patient subgroups after implementation of universal treatment, but heterogeneity in 12-month retention on ART between subgroups was unchanged. Instrumental variable analyses indicated that same-day ART initiation in routine settings led to a 15·8% increase (95% CI 12·1-19·5) in 12-month retention on ART. INTERPRETATION: UTT policies implemented in Zambia increased the rapidity and uptake of ART, as well as retention on ART at 12 months, although overall retention on ART remained suboptimal. UTT policies reduced disparities in treatment initiation, but not 12-month retention on ART. Natural experiments reveal both the anticipated and unanticipated effects of real-world implementation and indicate the need for new strategies leveraging the short-term effects of UTT to cultivate long-term treatment success. FUNDING: National Institutes of Health.
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 BH; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Infectious Diseases, University Hospital Bern, Bern, Switzerland.; Department of Medicine, University of Zambia, Lusaka, Zambia.; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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 FP; Mulenga L; Westfall AO; Warrier R; Mweemba A; Saag MS; Stringer JS; Eron JJ; Chi BH; Department of Internal Medicine, University of Texas at Austin, Austin, TX, USA.; UNC Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.; Department of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; School of Medicine, University of Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Geospatial Patterns of Progress towards UNAIDS "95-95-95" Targets and Community Vulnerability in Zambia.
(2023-Apr-26) Cuadros DF; Chowdhury T; Milali M; Citron D; Nyimbili S; Vlahakis N; Savory T; Mulenga L; Sivile S; Zyambo K; Bershteyn A; National HIV Program, Ministry of Health, Lusaka, Zambia.; Digital Epidemiology Laboratory, Digital Futures, University of Cincinnati, Cincinnati, OH, USA.; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.
In sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the "95-95-95" targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the "95-95-95" indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps. This study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimized hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access, and social determinants of healthcare utilization. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioral covariates and the three main outcomes of study. Varied progress towards the "95-95-95" targets were observed in different regions of Zambia. Each "95" displayed a unique geographic pattern, independent of HIV prevalence, resulting in four distinct geographic clusters. Factors associated with gaps in the "95s" include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on ART and having detectable viral loads. Our study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographic patterns and levels of performance in the "95-95-95" targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors, and developing innovative strategies to improve local HIV care continuum outcomes.
Geospatial patterns of progress towards UNAIDS '95-95-95' targets and community vulnerability in Zambia: insights from population-based HIV impact assessments.
(2023-Oct) Cuadros DF; Chowdhury T; Milali M; Citron DT; Nyimbili S; Vlahakis N; Savory T; Mulenga L; Sivile S; Zyambo KD; Bershteyn A; Digital Epidemiology Laboratory, Digital Futures, University of Cincinnati, Cincinnati, OH, USA.; National HIV Program, Ministry of Health, Lusaka, Zambia.; Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Digital Epidemiology Laboratory, Digital Futures, University of Cincinnati, Cincinnati, OH, USA diego.cuadros@uc.edu.
INTRODUCTION: In sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the '95-95-95' targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the '95-95-95' indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps. METHODS: This study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimised hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access and social determinants of healthcare utilisation. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioural covariates and the three main outcomes of study. RESULTS: Varied progress towards the '95-95-95' targets were observed in different regions of Zambia. Each '95' displayed a unique geographical pattern, independent of HIV prevalence, resulting in four distinct geographical clusters. Factors associated with gaps in the '95s' include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on antiretroviral therapy and having detectable viral loads. CONCLUSIONS: Our study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographical patterns and levels of performance in the '95-95-95' targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors and developing innovative strategies to improve local HIV care continuum outcomes.
Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia.
(2016) Wandeler G; Musukuma K; Zürcher S; Vinikoor MJ; Llenas-García J; Aly MM; Mulenga L; Chi BH; Ehmer J; Hobbins MA; Bolton-Moore C; Hoffmann CJ; Egger M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Nucleo do investigacão Operational de Pemba, Pemba, Mozambique.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, United States of America.; Institute for Infectious Diseases, University of Bern, Bern, Switzerland.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; SolidarMed, Ancuabe, Mozambique.; Department of Infectious diseases, University of Dakar, Dakar, Senegal.; Department of Medicine at University of Alabama, Birmingham, United States of America.; SolidarMed, Lucerne, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Johns Hopkins University School of Medicine, Baltimore, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS: We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS: Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION: One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.
High prevalence of binge drinking among people living with HIV in four African countries.
(2018-Dec) Nouaman MN; Vinikoor M; Seydi M; Ekouevi DK; Coffie PA; Mulenga L; Tanon A; Egger M; Dabis F; Jaquet A; Wandeler G; INSERM U1219 Bordeaux Population Health Research, ISPED, Université de Bordeaux, Bordeaux, France.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Département de santé publique, Faculté des Sciences de la santé, Université de Lomé, Lomé, Togo.; Zambia Ministry of Health, Lusaka, Zambia.; Programme PACCI, CHU de Treichville, Abidjan, Côte d'Ivoire.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Centre for Infectious Diseases Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; CHU de Treichville, Service de maladies infectieuses et tropicales, Abidjan, Côte d'Ivoire.; University Teaching Hospital, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Service de maladies infectieuses et tropicales, CRCF, CHU de Fann, Dakar, Sénégal.
INTRODUCTION: Excessive alcohol consumption leads to unfavourable outcomes in people living with HIV (PLHIV), including reduced adherence to antiretroviral therapy (ART) and engagement into care. However, there is limited information on alcohol consumption patterns among PLHIV in sub-Saharan Africa. METHODS: Using a cross-sectional approach, the Alcohol Use Disorders Identification Test (AUDIT-C) was administered to PLHIV attending HIV clinics in Côte d'Ivoire, Togo, Senegal and Zambia (2013 to 2015). Hazardous drinking was defined as an AUDIT-C score ≥4 for men or ≥3 for women, and binge drinking as ≥6 drinks at least once per month. The prevalence of binge drinking was compared to estimates from the general population using data from the World Health Organization. Factors associated with binge drinking among persons declaring any alcohol use in the past year were assessed using a logistic regression model to estimate odds ratio (OR) and their corresponding 95% confidence intervals (CI). RESULTS: Among 1824 PLHIV (median age 39 years, 62.8% female), the prevalence of hazardous alcohol use ranged from 0.9% in Senegal to 38.4% in Zambia. The prevalence of binge drinking ranged from 14.3% among drinkers in Senegal to 81.8% in Zambia, with higher estimates among PLHIV than in the general population. Male sex (OR 2.4, 95% CI 1.6 to 3.7), tobacco use (OR 1.7, 95% CI 1.0 to 2.9) and living in Zambia were associated with binge drinking. CONCLUSIONS: Alcohol consumption patterns varied widely across settings and binge drinking was more frequent in HIV-positive individuals compared to the general population. Interventions to reduce excessive alcohol use are urgently needed to optimize adherence in the era of universal ART.
High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia.
(2020-Jan-02) Chihota BV; Wandeler G; Chilengi R; Mulenga L; Chung RT; Bhattacharya D; Egger M; Vinikoor MJ; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.; Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Liver Center and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Ministry of Health, Lusaka, Zambia.; School of Medicine, University of Zambia, Lusaka, Zambia.; Institute of Social and Preventative Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.
How can Africa sustain its HIV response amid US aid cuts?
(2025-Mar-20) Mutale W; Semeere A; Bukusi EA; Ojji D; Venter F; Odeny T; Chilengi R; Mosepele M; Geng E; Sikazwe I; Bosomprah S; Mulenga L; Simitala F; Department of Medicine, Washington University in St Louis, St Louis, MO, USA.; Zambian National Public Health Institute, Lusaka, Zambia; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Center for Microbiology Research, KEMRI, Nairobi, Kenya; Division of Oncology, Washington University, St Louis, MO, USA.; Department of Health Policy and Management, School of Public Health, University of Zambia, Lusaka 10101, Zambia; Southern Africa Institute for Collaborative Research and Innovation Organisation (SAICRIO), Lusaka, Zambia. Electronic address: wmutale@yahoo.com.; University of Botswana, Gaborone, Botswana.; Department of Medicine and Makerere University Joint AIDS Program, Makerere University, Kampala, Uganda.; University of the Witwatersrand, Johannesburg, South Africa.; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Ministry of Health, Lusaka, Zambia.; Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.; Center for Microbiology Research, KEMRI, Nairobi, Kenya.; Department of Internal Medicine, Faculty of Clinical Sciences, College of Health Sciences, University of Abuja, Abuja, Nigeria.
Integrating isoniazid preventive therapy into the fast-track HIV treatment model in urban Zambia: A proof-of -concept pilot project.
(2023) Mukumbwa-Mwenechanya M; Mubiana M; Somwe P; Zyambo K; Simwenda M; Zongwe N; Kalunkumya E; Mwango LK; Rabkin M; Mpesela F; Chungu F; Mwanza F; Preko P; Bolton-Moore C; Bosomprah S; Sharma A; Morton K; Kasonde P; Mulenga L; Lingu P; Mulenga PL; ICAP at Columbia University and Departments of Medicine & Epidemiology, New York, New York, United States of America.; ICAP at Columbia University, Mbabane, Eswatini.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Network of Zambian People Living with HIV, Lusaka, Zambia.; Clinton Health Access, Lusaka, Zambia.; ICAP at Columbia University, Lusaka, Zambia.; Columbia University Mailman School of Public Health, New York, New York, United States of America.; Ministry of Health, Lusaka, Zambia.; CIHEB, Lusaka, Zambia.; JSI USAID SAFE, Lusaka, Zambia.; University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Treatment Advocacy and Literacy Campaign, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Most people living with HIV (PLHIV) established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models such as Fast Track (FT), where clients collect ART every 3-6 months and make clinical visits every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. Asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in FT HIV treatment model. We implemented and evaluated a proof-of-concept project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials, standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, 6-month supply of isoniazid and ART, aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1-5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher's exact test to determine variation by participant characteristics. Key lessons learned were synthesized from monthly meeting notes. 1,167 clients were screened with 818 (70.1%) enrolled, two thirds (66%) were female and median age 42 years. 738 (90.2%) completed 6-month IPT course and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were insignificant differences of outcomes by age or sex. Lessons learnt included promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating collaborative structured learning. Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.
Liver fibrosis in treatment-naïve HIV-infected and HIV/HBV co-infected patients: Zambia and Switzerland compared.
(2016-Oct) Wandeler G; Mulenga L; Vinikoor MJ; Kovari H; Battegay M; Calmy A; Cavassini M; Bernasconi E; Schmid P; Bolton-Moore C; Sinkala E; Chi BH; Egger M; Rauch A; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa.; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Medicine, University of Zambia, Lusaka, Zambia.; University Hospital Basel, Basel, Switzerland.; Department of Infectious Diseases, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. Electronic address: gilles.wandeler@ispm.unibe.ch.; Regional Hospital, Lugano, Switzerland.; Cantonal Hospital, St. Gallen, Switzerland.; University Hospital Lausanne, Lausanne, Switzerland.; Department of Medicine, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital and University of Bern, CH-3010 Bern, Switzerland.; University Hospital Geneva, Geneva, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To examine the association between hepatitis B virus (HBV) infection and liver fibrosis in HIV-infected patients in Zambia and Switzerland. METHODS: HIV-infected adults starting antiretroviral therapy in two clinics in Zambia and Switzerland were included. Liver fibrosis was evaluated using the aspartate aminotransferase-to-platelet-ratio index (APRI), with a ratio >1.5 defining significant fibrosis and a ratio >2.0 indicating cirrhosis. The association between hepatitis B surface antigen (HBsAg) positivity, HBV replication, and liver fibrosis was examined using logistic regression. RESULTS: In Zambia, 96 (13.0%) of 739 patients were HBsAg-positive compared to 93 (4.5%) of 2058 in Switzerland. HBsAg-positive patients were more likely to have significant liver fibrosis than HBsAg-negative ones: the adjusted odds ratio (aOR) was 3.25 (95% confidence interval (CI) 1.44-7.33) in Zambia and 2.50 (95% CI 1.19-5.25) in Switzerland. Patients with a high HBV viral load (≥20000 IU/ml) were more likely to have significant liver fibrosis compared to HBsAg-negative patients or patients with an undetectable viral load: aOR 3.85 (95% CI 1.29-11.44) in Zambia and 4.20 (95% CI 1.64-10.76) in Switzerland. In both settings, male sex was a strong risk factor for significant liver fibrosis. CONCLUSIONS: Despite the differences in HBV natural history between Sub-Saharan Africa and Europe, the degree of liver fibrosis and the association with important risk factors were similar.
Liver steatosis and metabolic dysfunction-associated fatty liver disease among HIV-positive and negative adults in urban Zambia.
(2022-Jul) Chihota BV; Riebensahm C; Muula G; Sinkala E; Chilengi R; Mulenga L; Bosomprah S; Vinikoor MJ; Bolton-Moore C; Egger M; Rauch A; Berzigotti A; Wandeler G; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Graduate School of Health Sciences, University of Bern, Bern, Switzerland.; Department of Medicine, The University of Alabama, Birmingham, Alabama, USA.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Biostatistics, University of Ghana, Accra, Ghana.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Ministry of Health, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia belinda.chihota@cidrz.org.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: The growing importance of non-communicable diseases (NCDs) and high HIV prevalence in urban African settings may increase the burden of metabolic dysfunction-associated fatty liver disease (MAFLD). We assessed liver steatosis among HIV-positive and negative adults in urban Zambia. METHODS: Adults 30 years and older who were newly diagnosed with HIV, or tested HIV-negative at two primary care clinics in Lusaka, Zambia, were assessed for liver steatosis. Cardiometabolic data were collected through comprehensive clinical and laboratory assessments. Transient elastography was performed to measure controlled-attenuation parameter (≥248 dB/m). We used multivariable logistic regression models to determine the factors associated with the presence of steatosis. RESULTS: We enrolled 381 patients, including 154 (40%) antiretroviral therapy-naïve people living with HIV (PLWH) with a median CD4+ count of 247 cells/mm CONCLUSIONS: The prevalence of liver steatosis in this urban cohort of HIV-positive and negative adults in Zambia was low, despite a large proportion of patients with high BMI and central obesity. Our study is among the first to report data on MAFLD among adults in Africa, demonstrating that metabolic risk factors are key drivers of liver steatosis and supporting the adoption of the criteria for MAFLD in African populations.