CIDRZ Research
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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 HIV programme sustainability in Southern and Eastern Africa and the changing role of external assistance for health.(2024-Jan-23) Neel AH; Rodríguez DC; Sikazwe I; Pillay Y; Barron P; Pereira SK; Makakole-Nene S; Bennett SC; Department of Global Health, Stellenbosch University, Stellenbosch, South Africa.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.; School of Public Health, University of the Witwatersrand, Johannesburg 2193, South Africa.; Centre for Infectious Disease Research in Zambia (CIDRZ), 34620 Lukasu Road, Mass Media, Lusaka 10101, Zambia.; SCMN Global Health Consulting, 261 Middel Street, Pretoria 0181, South Africa.High human immunodeficiency virus (HIV)-prevalence countries in Southern and Eastern Africa continue to receive substantial external assistance (EA) for HIV programming, yet countries are at risk of transitioning out of HIV aid without achieving epidemic control. We sought to address two questions: (1) to what extent has HIV EA in the region been programmed and delivered in a way that supports long-term sustainability and (2) how should development agencies change operational approaches to support long-term, sustainable HIV control? We conducted 20 semi-structured key informant interviews with global and country-level respondents coupled with an analysis of Global Fund budget data for Malawi, Uganda, and Zambia (from 2017 until the present). We assessed EA practice along six dimensions of sustainability, namely financial, epidemiological, programmatic, rights-based, structural and political sustainability. Our respondents described HIV systems' vulnerability to donor departure, as well as how development partner priorities and practices have created challenges to promoting long-term HIV control. The challenges exacerbated by EA patterns include an emphasis on treatment over prevention, limiting effects on new infection rates; resistance to service integration driven in part by 'winners' under current EA patterns and challenges in ensuring coverage for marginalized populations; persistent structural barriers to effectively serving key populations and limited capacity among organizations best positioned to respond to community needs; and the need for advocacy given the erosion of political commitment by the long-term and substantive nature of HIV EA. Our recommendations include developing a robust investment case for primary prevention, providing operational support for integration processes, investing in local organizations and addressing issues of political will. While strategies must be locally crafted, our paper provides initial suggestions for how EA partners could change operational approaches to support long-term HIV control and the achievement of universal health coverage.Item Long-term outcomes after new onset seizure in children living with HIV: A cohort study.(2024-Apr) Birbeck GL; Mwenechanya M; Ume-Ezeoke I; Mathews M; Bositis CM; Kalungwana L; Bearden D; Elafros M; Gelbard HA; Theodore WH; Koralnik IJ; Okulicz JF; Johnson BA; Musonda N; Siddiqi OK; Potchen MJ; Sikazwe I; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.; University Teaching Hospitals Neurology Research Office, Lusaka, Zambia.; Department of Biostatistics, University of Rochester, Rochester, New York, USA.; Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.; Department of Neurology, University of Rochester, Rochester, New York, USA.; Department of Medicine, San Antonio Military Medical Center, San Antonio, Texas, USA.; Department of Psychology, University of Zambia, Lusaka, Zambia.; Zambian College of Medicine and Surgery, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Clinical Epilepsy Section, US National Institute of Health, Bethesda, Maryland, USA.; Department of Imaging Sciences, University of Rochester, Rochester, New York, USA.; University Teaching Hospitals Children's Hospital, Lusaka, Zambia.; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Family and Community Medicine, University of California San Francisco, San Francisco, California, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.Item An exploration of multi-level factors affecting routine linkage to HIV care in Zambia's PEPFAR-supported treatment program in the treat all era.(2024) Chipungu J; Smith H; Mwamba C; Haambokoma M; Sharma A; Savory T; Musheke M; Pry J; Bolton C; Sikazwe I; Herce ME; Research Department, Social and Behavioral Science Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.Multiple steps from HIV diagnosis to treatment initiation and confirmed engagement with the health system are required for people living with HIV to establish full linkage to care in the modern treat all era. We undertook a qualitative study to gain an in-depth understanding of the impeding and enabling factors at each step of this linkage pathway. In-depth interviews were conducted with fifty-eight people living with HIV recruited from ten routine HIV care settings supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) in Lusaka, Zambia. Using a semi-structured interview guide informed by an established conceptual framework for linkage to care, questions explored the reasons behind late, missed, and early linkage into HIV treatment, as well as factors influencing the decision to silently transfer to a different clinic after an HIV diagnosis. We identified previously established and intersecting barriers of internal and external HIV-related stigma, concerns about ART side effects, substance use, uncertainties for the future, and a perceived lack of partner and social support that impeded linkage to care at every step of the linkage pathway. However, we also uncovered newer themes specific to the current test and treat era related to the rapidity of ART initiation and insufficient patient-centered post-test counseling that appeared to exacerbate these well-known barriers, including callous health workers and limited time to process a new HIV diagnosis before treatment. Long travel distance to the clinic where they were diagnosed was the most common reason for silently transferring to another clinic for treatment. On the other hand, individual resilience, quality counseling, patient-centered health workers, and a supportive and empathetic social network mitigated these barriers. These findings highlight potential areas for strengthening linkage to care and addressing early treatment interruption and silent transfer in the test and treat era in Zambia.Item Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.(2024-Jul) Sikazwe I; Musheke M; Chiyenu K; Ngosa B; Pry JM; Mulubwa C; Zimba M; Sakala M; Sakala M; Somwe P; Nyirenda G; Savory T; Bolton-Moore C; Herce ME; Tithandizeni Umoyo Network, Lusaka, Zambia.; Zambia Sex Workers Alliance, Lusaka, Zambia.; Department of Public Health Sciences, School of Medicine, University of California, Davis, California, USA.; Intersex Society of Zambia, Lusaka, Zambia.; Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA.; Division of Infectious Diseases, Department of Medicine, University of Alabama, Birmingham, Alabama, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.INTRODUCTION: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity. RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%). CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.Item Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.(2024-Jul) Hargreaves JR; Baptiste S; Bhattacharjee P; Cowan FM; Herce ME; Lauer K; Sikazwe I; Geng E; Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Liverpool School of Tropical Medicine, Liverpool, UK.; Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, USA.; International Treatment Preparedness Coalition, Johannesburg, South Africa.; CIDRZ, Lusaka, Zambia.; Institute for Global Public Health, University of Manitoba, Winnipeg, Manitoba, Canada.; Partners for Health and Development in Africa, Nairobi, Kenya.; Division of Infectious Diseases and Center for Dissemination and Implementation, Washington University in St. Lous, St. Louis, Missouri, USA.; CeSHHAR, Harare, Zimbabwe.INTRODUCTION: "Programme science" deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: (1) feasible to undertake, (2) useful, (3) rigorous, (4) real-world-relevant, (5) informative, and undertaken by (6) equitable partnerships. The acronym "FURRIE" is proposed to describe this set of six challenges. This paper discusses selected HIV/STI (sexually transmitted infection) programme science case studies to illustrate how programme science rises to the FURRIE challenges. DISCUSSION: One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, these data can be augmented through methods that reach potential clients of services who have not accessed services or been lost to follow-up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigour by limiting bias and confounding in the real-world context of programme science studies requires methodological innovation. Striving for scientific rigour can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the "real-world." Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. CONCLUSIONS: Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field.Item Health outcomes and cost impact of the new WHO 2013 guidelines on prevention of mother-to-child transmission of HIV in Zambia.(2014) Ishikawa N; Shimbo T; Miyano S; Sikazwe I; Mwango A; Ghidinelli MN; Syakantu G; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; National Center for Global Health and Medicine, Tokyo, Japan.; Ministry of Health, Lusaka, Zambia.; Pan American Health Organization, Washington, D.C., United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: Countries are currently progressing towards the elimination of new paediatric HIV infections by 2015. WHO published new consolidated guidelines in June 2013, which now recommend either 'Antiretroviral drugs (ARVs) for women living with HIV during pregnancy and breastfeeding (Option B)' or 'Lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV (Option B+)', while de facto phasing out Option A. This study examined health outcomes and cost impact of the shift to WHO 2013 recommendations in Zambia. METHODS: A decision analytic model was developed based on the national health system perspective. Estimated risk and number of cases of HIV transmission to infants and to serodiscordant partners, and proportions of HIV-infected pregnant women with CD4 count of ≤350 cells/mm3 to initiate ART were compared between 2010 Option A and the 2013 recommendations. Total costs of prevention of mother-to-child transmission of HIV (PMTCT) services per annual cohort of pregnant women, incremental cost-effectiveness ratio (ICER) per infection averted and quality-adjusted life-year (QALY) gained were examined. RESULTS: Our analysis suggested that the shift from 2010 Option A to the 2013 guidelines would result in a 33% reduction of the risk of HIV transmission among exposed infants. The risk of transmission to serodiscordant partners for a period of 24 months would be reduced by 72% with 'ARVs during pregnancy and breastfeeding' and further reduced by 15% with 'Lifelong ART'. The probability of HIV-infected pregnant women to initiate ART would increase by 80%. It was also suggested that while the shift would generate higher PMTCT costs, it would be cost-saving in the long term as it spares future treatment costs by preventing infections in infants and partners. CONCLUSION: The shift to the WHO 2013 guidelines in Zambia would positively impact health of family and save future costs related to care and treatment.Item Brain Imaging in New-Onset Seizure of Children Living With Human Immunodeficiency Virus in Zambia.(2024-Oct) Mohajeri S; Potchen M; Sikazwe I; Kampondeni S; Hoffman C; Bearden D; Kalungwana L; Musonda N; Mathews M; Mwenechanya M; Dallah I; Johnson B; Bositis C; Huang J; Birbeck GL; Center for Infectious Diseases Research in Zambia (CIDRZ), Lusaka, Zambia.; Department of Imaging Sciences, University of Rochester, Rochester, New York. Electronic address: sarahmohajeri29@gmail.com.; Department of Family and Community Medicine, University of California, San Francisco, San Francisco, California.; University Teaching Hospital-Children's Hospital, Lusaka, Zambia.; Department of Imaging Sciences, University of Rochester, Rochester, New York.; Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York.; University of Rochester School of Medicine, Rochester, New York.; Mpingwe Clinic, Blantyre, Malawi.; Department of Psychology, University of Zambia, Lusaka, Zambia.; Department of Neurology, Epilepsy, University of Rochester, Rochester, New York.; Department of Neurology, Pediatric, University of Rochester, Rochester, New York.; TrialSpark, New York, New York.; Department of Radiology, Michigan State University, East Lansing, Michigan.BACKGROUND: There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. METHODS: In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered. RESULTS: Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9). CONCLUSIONS: Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.Item Cognitive impairment and psychiatric morbidity in HIV+ Zambians with new-onset seizure.(2014-Dec) Kalungwana L; Elafros MA; Siddiqi OK; Bositis CM; Sikazwe I; Koralnik IJ; Theodore WH; Birbeck GL; Department of Psychology, University of Zambia, Lusaka, Zambia; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia; Division of NeuroVirology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Greater Lawrence Family Health Center, Lawrence, Massachusetts; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Neurology, Epilepsy Division, University of Rochester, Rochester, New York; Chikankata Epilepsy Care Team, Mazabuka, Zambia gretchen_birbeck@urmc.rochester.edu.; Department of Psychology, University of Zambia, Lusaka, Zambia; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia; Division of NeuroVirology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Greater Lawrence Family Health Center, Lawrence, Massachusetts; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Neurology, Epilepsy Division, University of Rochester, Rochester, New York; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)A prospective cohort study of new-onset seizure in people with human immunodeficiency virus (HIV) in Zambia is ongoing to determine the incidence of subsequent epilepsy and risk factors for epileptogenesis in this population. At enrollment, we evaluated this cohort for cognitive impairment and psychiatric morbidity. Over 50% of participants had cognitive impairment and significant psychiatric morbidity. Most participants had advanced HIV disease based on CD4+ T-cell count and World Health Organization stage, but we found no association between cognitive impairment or psychiatric morbidity and HIV disease staging.Item Trends in all-cause mortality during the scale-up of an antiretroviral therapy programme: a cross-sectional study in Lusaka, Zambia.(2014-Oct-01) Rathod SD; Chi BH; Kusanthan T; Chilopa B; Levy J; Sikazwe I; Mwaba P; Stringer JS; Department of Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, England .; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia .; Zambian Central Statistical Office, Lusaka, Zambia .; University of Zambia, Lusaka, Zambia .; Zambian Ministry of Health, Lusaka, Zambia .; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)OBJECTIVE: To follow the trends in all-cause mortality in Lusaka, Zambia, during the scale-up of a national programme of antiretroviral therapy (ART). METHODS: Between November 2004 and September 2011, we conducted 12 survey rounds as part of a cross-sectional study in Lusaka, with independent sampling in each round. In each survey, we asked the heads of 3600 households to state the number of deaths in their households in the previous 12 months and the number of orphans aged less than 16 years in their households and investigated the heads' knowledge, attitudes and practices related to human immunodeficiency virus (HIV). FINDINGS: The number of deaths we recorded - per 100 person-years - in each survey ranged from 0.92 (95% confidence interval, CI: 0.78-1.09) in September 2011, to 1.94 (95% CI: 1.60-2.35) in March 2007. We found that mortality decreased only modestly each year (mortality rate ratio: 0.98; 95% CI: 0.95-1.00; P = 0.093). The proportion of households with orphans under the age of 16 years decreased from 17% in 2004 to 7% in 2011. The proportions of respondents who had ever been tested for HIV, had a comprehensive knowledge of HIV, knew where to obtain free ART and reported that a non-pregnant household member was receiving ART gradually increased. CONCLUSION: The expansion of ART services in Lusaka was not associated with a reduction in all-cause mortality. Coverage, patient adherence and retention may all have to be increased if ART is to have a robust and lasting impact at population level in Lusaka.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 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.