Browsing by Author "Mulenga PL"

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A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.
(2010-Mar-12) Koethe JR; Westfall AO; Luhanga DK; Clark GM; Goldman JD; Mulenga PL; Cantrell RA; Chi BH; Zulu I; Saag MS; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.
Attrition from HIV treatment after enrollment in a differentiated service delivery model: A cohort analysis of routine care in Zambia.
(2023) Jo Y; Jamieson L; Phiri B; Grimsrud A; Mwansa M; Shakwelele H; Haimbe P; Mukumbwa-Mwenechanya M; Mulenga PL; Nichols BE; Rosen S; Department of Internal Medicine, Health Economics and Epidemiology Research Office, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Medicine, Section of Infectious Diseases, Boston Medical Center, Boston, MA, United States of America.; Clinton Health Access Initiative, Lusaka, Zambia.; Department of Medical Microbiology, Amsterdam University Medical Center, Amsterdam, Netherlands.; HIV Programmes and Advocacy, International AIDS Society, Cape Town, South Africa.; Ministry of Health, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Global Health, Boston University School of Public Health, Boston, MA, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Many sub-Saharan Africa countries are scaling up differentiated service delivery (DSD) models for HIV treatment to increase access and remove barriers to care. We assessed factors associated with attrition after DSD model enrollment in Zambia, focusing on patient-level characteristics. METHODS: We conducted a retrospective record review using electronic medical records (EMR) of adults (≥15 years) initiated on antiretroviral (ART) between 01 January 2018 and 30 November 2021. Attrition was defined as lost to follow-up (LTFU) or died by November 30, 2021. We categorized DSD models into eight groups: fast-track, adherence groups, community pick-up points, home ART delivery, extended facility hours, facility multi-month dispensing (MMD, 4-6-month ART dispensing), frequent refill care (facility 1-2 month dispensing), and conventional care (facility 3 month dispensing, reference group). We used Fine and Gray competing risk regression to assess patient-level factors associated with attrition, stratified by sex and rural/urban setting. RESULTS: Of 547,281 eligible patients, 68% (n = 372,409) enrolled in DSD models, most commonly facility MMD (n = 306,430, 82%), frequent refill care (n = 47,142, 13%), and fast track (n = 14,433, 4%), with <2% enrolled in the other DSD groups. Retention was higher in nearly all DSD models for all dispensing intervals, compared to the reference group, except fast track for the ≤2 month dispensing group. Retention benefits were greatest for patients in the extended clinic hours group and least for fast track dispensing. CONCLUSION: Although retention in HIV treatment differed by DSD type, dispensing interval, and patient characteristics, nearly all DSD models out-performed conventional care. Understanding the factors that influence the retention of patients in DSD models could provide an important step towards improving DSD implementation.
CD4+ response and subsequent risk of death among patients on antiretroviral therapy in Lusaka, Zambia.
(2009-Sep-01) Chi BH; Giganti M; Mulenga PL; Limbada M; Reid SE; Mutale W; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Where virologic monitoring is not routinely available, immunologic criteria are commonly used to determine treatment failure while on antiretroviral therapy (ART). However, few have studied CD4+ response and its relationship to subsequent clinical outcomes in a programmatic setting. METHODS: We analyzed cohort data from Zambia to investigate whether 6- and 12-month CD4+ response after ART initiation was associated with later mortality. We used Cox proportional hazards models that accounted for different strata of baseline CD4 counts and adjusted for age, sex, clinical stage, tuberculosis coinfection, baseline hemoglobin, initial ART regimen, and adherence behavior. RESULTS: We analyzed data from 2 cohorts, from 6 months onward (n = 24,366; median follow-up = 467 days, interquartile range 222-791) and from 12 months onward (n = 17,920; median follow-up = 423 days, interquartile range 191-689). In the post-6-month analysis, hazard for death was significantly higher when absolute CD4+ response was <100 cells per microliter [adjusted hazard ratio (AHR) = 2.25, 95% confidence interval (CI): 1.91 to 2.64], relative response was <10% above baseline (AHR = 2.60, 95% CI: 2.12 to 3.19), and absolute CD4+ count was <100 per microliter (AHR = 2.79, 95% CI: 2.26 to 3.45). In the post-12 month analysis, mortality was associated with rise in absolute CD4+ cell count <200 per microliter (AHR = 2.41, 95% CI: 1.83 to 3.17), relative rise in CD4+ cell count of <10% above baseline (AHR = 3.41, 95% CI: 2.51 to 4.64), and absolute CD4+ count at 12 months <100 per microliter (AHR = 4.11, 95% CI: 2.96 to 5.68). CONCLUSION: Commonly used definitions for immunologic treatment failure are associated with elevated mortality risk among patients on ART.
Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.
(2010-May-01) Chi BH; Mwango A; Giganti M; Mulenga LB; Tambatamba-Chapula B; Reid SE; Bolton-Moore C; Chintu N; Mulenga PL; Stringer EM; Sheneberger R; Mwaba P; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. METHODS: We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. RESULTS: Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. CONCLUSIONS: TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.
Effect of Enhanced Adherence Package on Early ART Uptake Among HIV-Positive Pregnant Women in Zambia: An Individual Randomized Controlled Trial.
(2021-Mar) Mubiana-Mbewe M; Bosomprah S; Kadota JL; Koyuncu A; Kusanathan T; Mweebo K; Musokotwane K; Mulenga PL; Chi BH; Vinikoor MJ; Centre for Infectious Disease Research in Zambia, Plot 34620 Off Alick Nkhata Road, P.O. Box 34681, Lusaka, Zambia. Mwangelwa.Mbewe@cidrz.org.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Department of Medicine, University of Alabama at Birmingham, Birmingham, USA.; Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, USA.; Department of Gender Studies, University of Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Plot 34620 Off Alick Nkhata Road, P.O. Box 34681, Lusaka, Zambia.; Prevention, Care and Treatment Branch, U.S. Centers for Disease Control and Prevention, Lusaka, Zambia.; Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA.; Directorate of Public Health, Zambian Ministry of Health, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.
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.
Six-month hemoglobin concentration and its association with subsequent mortality among adults on antiretroviral therapy in Lusaka, Zambia.
(2012-Sep-01) Giganti MJ; Limbada M; Mwango A; Moyo C; Mulenga LB; Guffey MB; Mulenga PL; Bolton-Moore C; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. giganticidrz@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Little is known about changes in hemoglobin concentration early in the course of antiretroviral therapy and its subsequent relation to survival. We analyzed data for 40,410 HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. Our main exposure of interest was 6-month hemoglobin, but we stratified our analysis by baseline hemoglobin to allow for potential effect modification. Patients with a 6-month hemoglobin <8.5 g/dL, regardless of baseline, had the highest hazard for death after 6 months (hazard ratio: 4.5; 95% confidence interval: 3.3 to 6.3). Future work should look to identify causes of anemia in settings such as ours and evaluate strategies for more timely diagnosis and treatment.