Browsing by Author "Sinkala E"

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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.
Care Continuum and Postdischarge Outcomes Among HIV-Infected Adults Admitted to the Hospital in Zambia.
(2019-Oct) Haachambwa L; Kandiwo N; Zulu PM; Rutagwera D; Geng E; Holmes CB; Sinkala E; Claassen CW; Mugavero MJ; Wa Mwanza M; Turan JM; Vinikoor MJ; Zambia National Public Health Institute, Lusaka, Zambia.; Center for Global Health and Quality, Georgetown University School of Medicine, Washington, District of Columbia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; University Teaching Hospital HIV AIDS Programme, Lusaka, Zambia.; Johns Hopkins University, Baltimore, Maryland.; School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.; School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Medicine, University of California at San Francisco, San Francisco, California.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; School of Medicine, University of Maryland at Baltimore, Baltimore, Maryland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: We characterized the extent of antiretroviral therapy (ART) experience and postdischarge mortality among hospitalized HIV-infected adults in Zambia. METHODS: At a central hospital with an opt-out HIV testing program, we enrolled HIV-infected adults (18+ years) admitted to internal medicine using a population-based sampling frame. Critically ill patients were excluded. Participants underwent a questionnaire regarding their HIV care history and CD4 count and viral load (VL) testing. We followed participants to 3 months after discharge. We analyzed prior awareness of HIV-positive status, antiretroviral therapy (ART) use, and VL suppression (VS; <1000 copies/mL). Using Cox proportional hazards regression, we assessed risk factors for mortality. RESULTS: Among 1283 adults, HIV status was available for 1132 (88.2%), and 762 (67.3%) were HIV-positive. In the 239 who enrolled, the median age was 36 years, 59.7% were women, and the median CD4 count was 183 cells/mm CONCLUSIONS: Most HIV-related hospitalizations and deaths may now occur among ART-experienced vs -naïve individuals in Zambia. Development and evaluation of inpatient interventions are needed to mitigate the high risk of death in the postdischarge period.
Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.
(2023-Dec) Musukuma-Chifulo K; Ghebremichael M; Chilyabanyama ON; Bates M; Munsaka S; Simuyandi M; Chisenga C; Tembo J; Sinkala E; Koralnik IJ; Dang X; Chilengi R; Siddiqi OK; Harvard Medical School and Ragon Institute of Mass General, MIT and Harvard, Boston, MA, USA.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Center for Vaccines and Virology Research, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.; HerpeZ, University Teaching Hospital, Lusaka, Zambia.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; School of Life & Environmental Sciences, University of Lincoln, Lincoln, UK.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, Ministry of Health, 10101, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.
Chronic hepatitis B virus monoinfection at a university hospital in Zambia.
(2018-Sep-27) Vinikoor MJ; Sinkala E; Kanunga A; Muchimba M; Nsokolo B; Chilengi R; Wandeler G; Mulenga J; Chisenga T; Bhattacharya D; Saag MS; Foster G; Fried MW; Kelly P; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United States.; Zambian Ministry of Health, Ndeke House, Lusaka 30205, Zambia.; Zambia National Blood Transfusion Service, Private Bag RW1X Ridgeway, Lusaka 50110, Zambia.; Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90035, United States.; Tropical Gastroenterology and Nutrition Group, School of Medicine, University of Zambia, Lusaka 50110, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern 3012, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka 34681, Zambia.; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London E1 2AT, United Kingdom.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
AIM: To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia. METHODS: Hepatitis B surface antigen-positive adults ( RESULTS: The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified CONCLUSION: Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.
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.
Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia.
(2020) Vinikoor MJ; Sinkala E; Kanunga A; Muchimba M; Zanolini A; Saag M; Pry J; Nsokolo B; Chisenga T; Kelly P; Zambian Ministry of Health, Lusaka, Zambia.; Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.; Department for International Development, Dar Es Salaam, Tanzania.; University of California at Davis, Davis, California, United States of America.; Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia. MATERIALS AND METHODS: Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines. RESULTS: Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99-1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81-0.98). Trends toward higher HBsAg-positivity were also seen at ages 30-39 years (AOR, 2.11; 95% CI, 0.96-4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93-3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART). CONCLUSION: Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.
Epstein-Barr Virus Detection in the Central Nervous System of HIV-Infected Patients.
(2022-Sep-22) Musukuma-Chifulo K; Siddiqi OK; Chilyabanyama ON; Bates M; Chisenga CC; Simuyandi M; Sinkala E; Dang X; Koralnik IJ; Chilengi R; Munsaka S; HerpeZ Infection Research and Training, University Teaching Hospital, Lusaka Private Bag RW1X Ridgeway, Lusaka P.O. Box 10101, Zambia.; Department of Biomedical Science, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.; School of Life & Environmental Sciences, University of Lincoln, Lincoln LN6 7TS, UK.; Department of Internal Medicine, School of Medicine, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Department of Internal Medicine, Center for Virology and Vaccines Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Simply detecting Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) is insufficient to diagnose EBV-associated diseases. The current literature around EBV-DNA detection from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-positive non-lymphoma patients was systematically reviewed and a meta-analysis reporting the estimated pooled prevalence in this population when PCR methods are employed, targeting different sequence segments within the EBV genome, was conducted. Using a combination of three key concepts-Epstein-Barr virus detection, central nervous system disease, and human cerebrospinal fluid-and their MeSH terms, the PubMed database was searched. A total of 273 papers reporting the detection of EBV in CNS were screened, of which 13 met the inclusion criteria. The meta-analysis revealed a pooled prevalence of EBV-DNA in CSF of 20% (CI: 12-31%). The highest pooled prevalence was from studies conducted on the African population at 39% (CI: 27-51%). The investigation of the presence of EBV-DNA in the CSF was also very varied, with several gene targets used. While most patients from the articles included in this review and meta-analysis were symptomatic of CNS disorders, the pathogenicity of EBV in non-lymphoma HIV patients when detected in CSF has still not been determined. The presence of EBV-DNA in the CNS remains a concern, and further research is warranted to understand its significance in causing CNS disorders.
Hepatitis B Therapy as HIV Prevention in Africa: A Case Series From Zambia.
(2019-Jan) Vinikoor MJ; Sinkala E; Chihota B; Kanunga A; Wandeler G; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia.
(2023-Nov-01) Muula GK; Bosomprah S; Sinkala E; Nsokolo B; Musonda T; Hamusonde K; Bhattacharya D; Lauer G; Chung RT; Mulenga LB; Wandeler G; Vinikoor MJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, University of California at Los Angeles, Los Angeles, California.; Department of Medicine, Levy Mwanawasa Medical University, Lusaka, Zambia.; School of Public Health, University of Ghana, Accra, Ghana.; Department of Medicine, University of Zambia.; Division of Gastroenterology, Massachusetts General Hospital, Boston, USA.; Department of Infectious Diseases, Bern University Hospital.; Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University Teaching Hospital, Zambian Ministry of Health.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. METHODS: In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers. RESULTS: Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/μl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/μl. HIV was not associated with markers of fibrosis or ALT. DISCUSSION: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.
Hepatosplenic schistosomiasis in Zambian adults is characterized by increased liver stiffness: A nested case-control study.
(2020-Jul) Sinkala E; Vinikoor M; Miyanda Siyunda A; Zyambo K; Besa E; Nsokolo B; Wandeler G; Foster GR; Kelly P; Department of Medicine, University of Alabama at Birmingham, Birmingham, USA.; Institute of Social and Preventive Medicine, University of Bern, Switzerland.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Cirrhosis commonly complicates portal hypertension worldwide but in Zambia hepatosplenic schistosomiasis (HSS) dominates as the cause of portal hypertension. We need easier and non-invasive ways to assess HSS. Transient elastography (TE), a measure of liver stiffness can diagnose liver cirrhosis. TE remains unexplored in HSS patients, who generally have normal liver parenchyma. We aimed to explore liver stiffness in HSS. This nested case control study was conducted at the University Teaching Hospital, Lusaka, Zambia between January 2015 and January 2016. We enrolled 48 adults with HSS and 22 healthy controls. We assessed liver stiffness using TE while plasma hyaluronan was used to assess liver fibrosis. Plasma tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) were used to assess inflammation. The median (interquartile range) liver stiffness was higher in patients, 9.5 kPa (7.8, 12.8) than in controls, 4.7 kPa (4.0, 5.4),
Impact of Antiretroviral Therapy on Liver Fibrosis Among Human Immunodeficiency Virus-Infected Adults With and Without HBV Coinfection in Zambia.
(2017-May-15) Vinikoor MJ; Sinkala E; Chilengi R; Mulenga LB; Chi BH; Zyambo Z; Hoffmann CJ; Saag MS; Davies MA; Egger M; Wandeler G; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill.; Department of Medicine, Johns Hopkins University, Baltimore, Maryland.; Department of Medicine, University of Alabama at Birmingham.; Institute of Social and Preventive Medicine, University of Bern, Switzerland.; School of Medicine, University of Zambia, and.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland.; Centre for Infectious Disease Research in Zambia.; School of Public Health and Family Medicine, University of Cape Town, South Africa.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: We investigated changes in hepatic fibrosis, based on transient elastography (TE), among human immunodeficiency virus (HIV)-infected patients with and without hepatitis B virus (HBV) coinfection on antiretroviral therapy (ART) in Zambia. METHODS: Patients' liver stiffness measurements (LSM; kiloPascals [kPa]) at ART initiation were categorized as no or minimal fibrosis (equivalent to Metavir F0-F1), significant fibrosis (F2-F3), and cirrhosis (F4). TE was repeated following 1 year of ART. Stratified by HBV coinfection status (hepatitis B surface antigen positive at baseline), we described LSM change and the proportion with an increase/decrease in fibrosis category. Using multivariable logistic regression, we assessed correlates of significant fibrosis/cirrhosis at 1 year on ART. RESULTS: Among 463 patients analyzed (61 with HBV coinfection), median age was 35 years, 53.7% were women, and median baseline CD4+ count was 240 cells/mm3. Nearly all (97.6%) patients received tenofovir disoproxil fumarate-containing ART, in line with nationally recommended first-line treatment. The median LSM change was -0.70 kPa (95% confidence interval, -3.0 to +1.7) and was similar with and without HBV coinfection. Significant fibrosis/cirrhosis decreased in frequency from 14.0% to 6.7% (P < .001). Increased age, male sex, and HBV coinfection predicted significant fibrosis/cirrhosis at 1 year (all P < .05). CONCLUSION: The percentage of HIV-infected Zambian adults with elevated liver stiffness suggestive of significant fibrosis/cirrhosis decreased following ART initiation-regardless of HBV status. This suggests that HIV infection plays a role in liver inflammation. HBV-coinfected patients were more likely to have significant fibrosis/cirrhosis at 1 year on ART. CLINICAL TRIALS REGISTRATION: NCT02060162.
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.
Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.
(2024-Jun-14) Vinikoor MJ; Hamusonde K; Muula G; Asombang M; Riebensahm C; Chitundu H; Sunkuntu-Sichizya V; Bhattacharya D; Sinkala E; Lauer G; Chung R; Mbewe W; Egger M; Bosomprah S; Wandeler G; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Ghana.; Kanyama Level 1 Hospital, Ministry of Health, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; Department of Radiology, University Teaching Hospital, Lusaka, Zambia.; Research Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. CONCLUSIONS: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.
New Window Into Hepatitis B in Africa: Liver Sampling Combined With Single-Cell Omics Enables Deep and Longitudinal Assessment of Intrahepatic Immunity in Zambia.
(2024-Nov-15) Musonda T; Wallace MS; Patel H; Martin OP; Oetheimer C; Mwakamui S; Sinkala E; Nsokolo B; Kanunga A; Lauer G; Chung RT; Wandeler G; Bhattacharya D; Kelly P; Alatrakchi N; Vinikoor MJ; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, University of California Los Angeles, Los Angeles, California, USA.; Blizard Institute, Queen Mary University of London, London, United Kingdom.; Tropical Gastroenterology and Nutrition Group, University of Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Medicine, Levy Mwanawasa University Teaching Hospital, Lusaka, Zambia.; Division of Infectious Diseases, University of Alabama Birmingham, Birmingham, Alabama, USA.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
In Lusaka, Zambia, we introduced liver fine-needle aspiration biopsy (FNAB) into a research cohort of adults with treatment-naive chronic hepatitis B virus (HBV) infection, with and without human immunodeficiency virus (HIV) coinfection, as well as with acute HBV infection. From 117 enrollment and 47 longitudinal FNABs (at 1-year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single-cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.
Propranolol Reduces Portal Vein Diameter in Schistosomal Liver Disease with Portal Hypertension: A Prospective Cohort Study.
(2020-Apr) Sinkala E; Vinikoor M; Zyambo K; Besa E; Nsokolo B; Kelly P; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Department of Internal Medicine, Tropical Gastroenterology and Nutritional Group, University of Zambia, Lusaka, Zambia.; Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Hepatosplenic schistosomiasis (HSS) complicates portal hypertension, leading to life-threatening variceal bleeding. Variceal bleeding is associated with increased portal vein diameter (PVD). Beta-blockers prevent variceal bleeding. It is unclear whether beta-blockers such as propranolol can reduce PVD in HSS. We aimed to explore the effect of propranolol on PVD in HSS. A longitudinal study was conducted at the University Teaching Hospital, Zambia, as an extension of a clinical trial of rifaximin undertaken to test the hypothesis that rifaximin could reduce bacterial translocation in HSS. We randomized 85 adults to either rifaximin and standard care, or propranolol-based standard care only for 42 days. We then followed up all the patients on propranolol up to day 180. We used ultrasound to measure PVD at baseline and day 180. The primary outcome was reduction in PVD. Beta-blockade and splenic size reduction were secondary outcomes. Portal vein diameter reduced after 180 days of propranolol therapy from median 12 mm (interquartile range (IQR): 11-14) to median 10 mm (IQR: 9-13) (
Response to 'Is AST-to-platelet ratio index a reliable tool in HIV patients in Africa?'.
(2015-Aug) Vinikoor MJ; Sinkala E; Wandeler G; Chi BH; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.; Department of Infectious Diseases, University Hospital Bern, Bern, Switzerland.; Department of Medicine, University of Zambia, Lusaka, Zambia.; University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.
(2018-Apr) Sinkala E; Zyambo K; Besa E; Kaonga P; Nsokolo B; Kayamba V; Vinikoor M; Zulu R; Bwalya M; Foster GR; Kelly P; Paediatric Centre of Excellence Laboratory, University Teaching Hospital, Lusaka, Zambia.; Department of Internal Medicine, Tropical Gastroenterology & Nutritional Group, University of Zambia, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom.; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196),
Screening for hepatocellular carcinoma among adults with HIV/HBV co-infection in Zambia: a pilot study.
(2022-Mar) Riebensahm C; Chitundu H; Muula G; Chihota B; Sinkala E; Sunkutu V; Maurer MH; Dufour JF; Berzigotti A; Egger M; Bolton-Moore C; Vinikoor M; Wandeler G; Department for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Hepatology, Department of BioMedical Research, University of Bern, Bern, Switzerland.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: carlotta.riebensahm@insel.ch.; Department of Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Centre for Infectious Diseases Research, University of Cape Town, Cape Town, Republic of South Africa.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia; Department of Medicine, University of Alabama, Birmingham, AL, USA.; Department of Radiology, University Teaching Hospital, Lusaka, Zambia.; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Hepatology, Department of BioMedical Research, University of Bern, Bern, Switzerland.; Department of Medicine, University Teaching Hospital, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). An HCC screening initiative was piloted in an established cohort of individuals co-infected with human immunodeficiency virus (HIV) and HBV on antiretroviral therapy (ART) at two outpatient clinics in Lusaka, Zambia. METHODS: All patients underwent abdominal ultrasound (AUS) and transient elastography. RESULTS: Among 279 patients co-infected with HIV/HBV, 165 (59.1%) were men, median age was 34 years [interquartile range (IQR) 28-39 years] and median CD4 count was 246 cells/µL (IQR 112-355 cells/µL) at ART initiation. While 102 (55.7%) individuals had elevated transaminases, 114 (59.7%) had HBV levels >2000 IU/mL and 59 (24.6%) had significant fibrosis. At their first AUS measurement, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) had periportal fibrosis. Five patients had a liver lesion >1 cm, an indication for confirmatory imaging. CONCLUSIONS: In one of the first HCC screening initiatives in SSA, 2% of patients co-infected with HIV/HBV had significant liver lesions, and one-quarter had findings suggestive of schistosomiasis-induced liver damage.