Browsing by Author "Egger M"

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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.
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.
Authors' Reply: Early Initiation of Antiretroviral Therapy Among Young Children: A Long Way to Go.
(2015-Oct-01) Koller M; Patel K; Chi BH; Wools-Kaloustian K; Dicko F; Chokephaibulkit K; Chimbetete C; Hazra R; Ayaya S; Leroy V; Trong HK; Egger M; Davies MA; *Institute of Social & Preventive Medicine (ISPM), University of Bern, Switzerland †Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia §Department of Medicine, Indiana University School of Medicine, Indianapolis, IN ‖Department of Pediatrics, Gabriel Toure Hospital, Bamako, Mali ¶Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand #Newlands Clinic, Harare, Zimbabwe **Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD ††Department of Pediatrics, College of Health Sciences, Moi University, Kenya ‡‡INSERM, French National Institute for Health and Medical Research, U897, Bordeaux, France §§Children's Hospital 1, Ho Chi Minh City, Vietnam ‖‖School of Public Health and Family Medicine, University of Cape Town Faculty of Health Sciences, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Awareness and management of elevated blood pressure among human immunodeficiency virus-infected adults receiving antiretroviral therapy in urban Zambia: a call to action.
(2017) Bauer S; Wa Mwanza M; Chilengi R; Holmes CB; Zyambo Z; Furrer H; Egger M; Wandeler G; Vinikoor MJ; a Department of Infectious Diseases , Bern University Hospital, University of Bern , Bern , Switzerland.; e Department of Medicine , University of Alabama at Birmingham , Birmingham , USA.; b Centre for Infectious Diseases Research in Zambia , Lusaka , Zambia.; f School of Medicine , University of Zambia , Lusaka , Zambia.; d Institute of Social and Preventive Medicine , University of Bern , Bern , Switzerland.; c School of Medicine , Johns Hopkins University , Baltimore , USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The prevalence of high blood pressure (HBP) and hypertension (HTN), awareness of the diagnoses, and use of anti-hypertensive drugs were examined among human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) in Zambia's capital Lusaka. Within a prospective cohort based at two public sector ART clinics, BP was measured at ART initiation and every 6 months thereafter as a routine clinic procedure. Predictors of HBP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) during one year on ART were analyzed using logistic regression, and the proportion with HTN (2+ episodes of HBP >3 months apart) described. A phone survey was used to understand patient awareness of HBP, use of anti-hypertensive drugs, and history of cardiovascular events (CVE; myocardial infarction or stroke). Among 896 cohort participants, 887 (99.0%) had at least one BP measurement, 98 (10.9%) had HBP, and 57 (6.4%) had HTN. Increasing age (10-year increase in age: adjusted odds ratio [AOR] = 1.50; 95% confidence interval [CI] 1.20-1.93), male sex (AOR = 2.33, 95% CI 1.43-3.80), and overweight/obesity (AOR = 4.07; 95% CI 1.94-8.53) were associated with HBP. Among 66 patients with HBP, 35 (53.0%) reported awareness of the condition, and nine (25.7%) of these reported having had a CVE. Only 14 (21.2%) of those reached reported ever taking an anti-hypertensive drug, and one (1.5%) was currently on treatment. These data suggest that major improvements are needed in the management of HBP among HIV-infected individuals in settings such as Zambia.
Cardiovascular Involvement in Tuberculosis Patients Treated in Southern Africa.
(2025-Jan) Samim D; Muula G; Banholzer N; Chibomba D; Xulu S; Bolton C; Evans D; Perrig L; De Marchi S; Günther G; Egger M; Pilgrim T; Fenner L; Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, Republic of South Africa.; Department of Cardiology, Helen Joseph Clinic, Johannesburg, Republic of South Africa.; Department of Pulmonology and Allergology, Inselspital, University Hospital of Bern, Bern, Switzerland.; University Teaching Hospital, Department of Internal Medicine, Lusaka, Zambia.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
BACKGROUND: Tuberculosis (TB) is the leading cause of death among people with HIV and a major global health challenge. Subclinical cardiovascular manifestations of TB are poorly documented in high TB and HIV burden countries. OBJECTIVES: The purpose of this study was to quantify the prevalence of cardiovascular involvement in TB patients and investigate changes after completion of anti-TB treatment. METHODS: HIV-positive and HIV-negative patients diagnosed with pulmonary TB between October 2022 and November 2023 were enrolled from 2 tertiary care hospitals in Zambia and South Africa. Standardized transthoracic echocardiography (TTE) was conducted at TB diagnosis and after 6 months of anti-TB treatment. Cross-sectional and longitudinal analyses assessed pericardial effusion, thickening, or calcification, with and without signs of pericardial constriction. RESULTS: A total of 286 TB patients (218 [76%] men, 109 [38%] people with HIV, median age 35 years) underwent TTE at TB diagnosis, of whom 105 participants had a second TTE after completion of treatment. At TB diagnosis, 134 (47%) had pericardial effusions, 86 (30%) thickening, 7 (2%) calcifications, 103 (42%) signs of constriction, and 13 (12%) had definite diagnosis of constriction. After TB treatment, pericardial effusions (47% vs 16%, CONCLUSIONS: Cardiac involvement is frequent in newly diagnosed TB patients. Early pericardial changes may be reversed with anti-TB treatment. Echocardiographic screening facilitates early detection and timely management of cardiovascular involvement in TB patients.
Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.
(2024-Aug) Nyakato P; Schomaker M; Boulle A; Euvrard J; Wood R; Eley B; Prozesky H; Christ B; Anderegg N; Ayakaka I; Rafael I; Kunzekwenyika C; Moore CB; van Lettow M; Chimbetete C; Mbewe S; Ballif M; Egger M; Yiannoutsos CT; Cornell M; Davies MA; R.M Fairbanks, School of Public Health, Department of Biostatistics, Indiana University, Indianapolis, Indiana, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; SolidarMed, Pemba, Mozambique.; Centre for Infectious Disease Epidemiology and Research, School of Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; SolidarMed, Masvingo, Zimbabwe.; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa.; Lighthouse Trust Clinic, Lilongwe, Malawi.; SolidarMed, Maseru, Lesotho.; Khayelitsha ART Programme, Cape Town, South Africa.; Western Cape Government: Health and Wellness, Cape Town, South Africa.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Madiro, Toronto, Canada.; Department of Statistics, Ludwig-Maximilians-Universität München, Munich, Germany.; Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Gugulethu HIV Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; Dignitas International, Zomba, Malawi.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.
Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.
(2014-Nov) Ballif M; Nhandu V; Wood R; Dusingize JC; Carter EJ; Cortes CP; McGowan CC; Diero L; Graber C; Renner L; Hawerlander D; Kiertiburanakul S; Du QT; Sterling TR; Egger M; Fenner L; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Centre Intégré de Recherches Biocliniques, Abidjan, Côte d'Ivoire.; United States Agency for International Development Academic Model Providing Access to Healthcare, Eldoret, Kenya.; Vanderbilt University School of Medicine, Nashville, Tennessee, USA.; Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.; Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Children's Hospital, Ho Chi Minh City, Viet Nam.; Women's Equity in Access to Care & Treatment, Kigali, Rwanda.; Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.; University of Ghana Medical School, Accra, Ghana.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Chile School of Medicine, Santiago, Chile.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.
Drug Resistance in People With Viremia on Dolutegravir-based Antiretroviral Therapy in Sub-Saharan Africa: The DTG RESIST Study.
(2025-May-20) Loosli T; Moore CB; Buzaalirwa L; Byakwaga H; Çelikağ İ; Chimbetete C; Ebasone PV; Giandhari J; Han N; Huwa J; Kasozi C; Mafoua A; Messou E; Minga A; Muula G; Muyindike W; Ndala ACM; Sauermann M; Semeere A; Singh L; Kouyos RD; Lessells R; Egger M; Centre de Traitement Ambulatoire, Brazzaville, Republic of the Congo.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; Centre National de Transfusion Sanguine, Abidjan, Côte d'Ivoire.; Center for AIDS Research, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Centre de Traitement Ambulatoire, Pointe Noire, Republic of the Congo.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.; Lighthouse Trust, Lilongwe, Malawi.; Centre de Prise en Charge, de Recherche et de Formation, Abidjan, Côte d'Ivoire.; KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa.; Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.; Public Health Department, Regional Referral Hospital, Masaka, Uganda.; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.; Infectious Diseases Institute, Makerere University, Kampala, Uganda.; Hôpital Jamot, Yaoundé and Regional Hospital, Limbé, Cameroon.; AIDS Healthcare Foundation Uganda Cares, Masaka, Uganda.; Centre for Infectious Disease Epidemiology and Research, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Dolutegravir resistance is an increasing concern. An analysis of the DTG RESIST study found that among 227 integrase sequences from 7 African countries (all non-B subtypes), 59 (26.0%) had at least 1 major drug resistance mutation (primarily G118R and E138A/K/T), with 49 (21.6%) predicted to have high-level resistance to dolutegravir.
Extending Visit Intervals for Clinically Stable Patients on Antiretroviral Therapy: Multicohort Analysis of HIV Programs in Southern Africa.
(2019-Aug-01) Haas AD; Johnson LF; Grimsrud A; Ford N; Mugglin C; Fox MP; Euvrard J; van Lettow M; Prozesky H; Sikazwe I; Chimbetete C; Hobbins M; Kunzekwenyika C; Egger M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; 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.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; Global Health, Boston University School of Public Health, Boston, MA.; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Newlands Clinic, Harare, Zimbabwe.; Department of HIV/AIDS World Health Organization, Geneva, Switzerland.; SolidarMed, Masvingo, Zimbabwe.; International AIDS Society, Cape Town, South Africa.; Division of Infectious Diseases, Department of Medicine, Tygerberg Academic Hospital, University of Stellenbosch, Cape Town, South Africa.; Dignitas International, Zomba, Malawi.; SolidarMed, Lucerne, Switzerland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The World Health Organization recommends differentiated antiretroviral therapy (ART) delivery with longer visit intervals for clinically stable patients. We examined time trends in visit frequency and associations between criteria for clinical stability and visit frequency in ART programs in Southern Africa. METHODS: We included adults on ART from 4 programs with viral-load monitoring, 2 programs with CD4 monitoring, and 4 programs with clinical monitoring of ART. We classified patients as clinically stable based on virological (viral load <1000 copies/mL), immunological (CD4 >200 cells/µL), or clinical (no current tuberculosis) criteria. We used Poisson regression and survival models to examine associations between criteria for clinical stability and the rate of clinic visits. RESULTS: We included 180,837 patients. There were trends toward fewer visits in more recent years and with longer ART duration. In all ART programs, clinically stable patients were seen less frequently than patients receiving failing ART, but the strength of the association varied. Adjusted incidence rate ratios comparing visit rates for stable patients with patients on failing ART were 0.82 (95% confidence interval: 0.73 to 0.90) for patients classified based on the virological criterion, 0.81 (0.69 to 0.93) for patients classified based on the clinical criterion, and 0.90 (0.85 to 0.96) for patients classified based on the immunological criterion for stability. CONCLUSION: Differences in visit rates between stable patients and patients failing ART were variable and modest overall. Larger differences were seen in programs using virological criteria for clinical stability than in programs using immunological criteria. Greater access to routine viral-load monitoring may increase scale-up of differentiated ART delivery.
Field evaluation of nanopore targeted next-generation sequencing to predict drug-resistant tuberculosis from native sputum in South Africa and Zambia.
(2025-Mar-12) Schwab TC; Joseph L; Moono A; Göller PC; Motsei M; Muula G; Evans D; Neuenschwander S; Günther G; Bolton C; Keller PM; Ramette A; Egger M; Omar SV; Fenner L; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Population Health Sciences, University of Bristol, Bristol, United Kingdom.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Pulmonology and Allergology, Inselspital Universitatsspital Bern, Bern, Switzerland.; Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.; Department of Medical Science, Faculty of Health Sciences, University of Namibia, Windhoek, Namibia.; Institute for Infectious Diseases, University of Bern Institute for Infectious Diseases, Bern, Switzerland.; Clinical Bacteriology/Mycology, University Hospital Basel, Basel, Switzerland.; Centre for Infectious Disease Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa.; Centre for Tuberculosis, National & WHO Supranational TB Reference Laboratory, a division of the National Health Laboratory Services, National Institute for Communicable Diseases, Johannesburg, South Africa.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Rapid and comprehensive drug susceptibility testing (DST) is essential for diagnosing and treating drug-resistant tuberculosis effectively, and next-generation sequencing can be an effective genotypic DST method. We implemented and evaluated the performance of a nanopore targeted sequencing assay, called the Tuberculosis Drug Resistance Test (TBDR, Oxford Nanopore Diagnostics, Ltd., United Kingdom), which predicts drug resistance to 16 TB drugs, at a South African reference laboratory and a district diagnostic laboratory in Zambia. We compared the sequencing success rates between unprocessed and decontaminated sputum samples and determined the diagnostic accuracy against local DST (Xpert MTB/RIF Ultra, Xpert MTB/XDR, and BD BACTEC MGIT phenotypic DST). We prospectively sequenced 236 samples and have 148 samples with sequencing results from unprocessed and decontaminated sputum. We obtained successful sequencing results from 66.4% (94/148) unprocessed sputum samples and 75% (111/148) decontaminated samples. Sequencing success rates at the two sites differed, with 50.7% (36/71) successful sequencing results from unprocessed sputum in Zambia and 75.3% (58/77) in South Africa. Samples with "low" bacterial load, measured by Xpert MTB/RIF Ultra, tended to produce fewer successful sequencing results. TBDR sequencing predicted resistances in 48 samples, detecting resistance for rifampicin (
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.
High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study.
(2022-Dec-15) Nyakato P; Christ B; Anderegg N; Muhairwe J; Jefferys L; van Dijk J; Vinikoor MJ; van Lettow M; Chimbetete C; Phiri SJ; Egger M; Ballif M; Yiannoutsos CT; Schomaker M; Kassanjee R; Davies MA; Cornell M; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Newlands Clinic, Harare, Zimbabwe.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine.; SolidarMed, Maseru, Lesotho.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Lighthouse Trust Clinic, Lilongwe, Malawi.; SolidarMed, Pemba, Mozambique.; SolidarMed, Masvingo, Zimbabwe.; R.M. Fairbanks School of Public Health, Department of Biostatistics, Indiana University, Indianapolis, IN; and.; Dignitas International, Zomba, Malawi.; Department of Statistics, Ludwig-Maximilians-Universität München, München, Germany.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Antiretroviral therapy program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS: We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS: Among 680 children and youth aged <25 years on antiretroviral therapy who were lost and traced in Southern Africa between October 2017 and November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20-24 years compared with infants aged <2 years [adjusted hazard ratio: 0.40 (95% confidence interval: 0.31 to 0.51)]. CONCLUSIONS: Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality.
Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.
(2015-Jan-01) Koller M; Patel K; Chi BH; Wools-Kaloustian K; Dicko F; Chokephaibulkit K; Chimbetete C; Avila D; Hazra R; Ayaya S; Leroy V; Truong HK; Egger M; Davies MA; *Institute of Social & Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; †Department of Epidemiology, Harvard School of Public Health, Boston, MA; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; ‖Department of Pediatrics, Gabriel Toure Hospital, Bamako, Mali; ¶Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; #Newlands Clinic, Harare, Zimbabwe; **Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD; ††Department of Pediatrics, College of Health Sciences, Moi University, Kenya; ‡‡INSERM, French National Institute for Health and Medical Research, U897, Bordeaux, France; §§Children's Hospital 1, Ho Chi Minh City, Vietnam; and ‖‖School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. METHODS: We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. RESULTS: A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. CONCLUSIONS: Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.
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.
Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.
(2015-Nov-01) Koller M; Fatti G; Chi BH; Keiser O; Hoffmann CJ; Wood R; Prozesky H; Stinson K; Giddy J; Mutevedzi P; Fox MP; Law M; Boulle A; Egger M; *Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; †Kheth'Impilo, Cape Town, South Africa; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §Aurum Institute for Health Research, Johannesburg, South Africa; ‖Gugulethu ART Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; ¶Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; #Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; **Sinikithemba Clinic, McCord Hospital, Durban, South Africa; ††Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; ‡‡Health Economics and Epidemiology Research Office, University of the Witwatersrand, Johannesburg, South Africa; §§Center for Global Health & Development and Department of Epidemiology, Boston University, Boston, MA; ‖‖Biostatistics and Databases Program, The Kirby Institute, Faculty of Medicine, The University of New South Wales, Sydney, Australia; and ¶¶Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS: We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS: In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS: CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.
Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral therapy in Southern Africa: a prospective multicohort study.
(2014-Dec-15) Rohner E; Valeri F; Maskew M; Prozesky H; Rabie H; Garone D; Dickinson D; Chimbetete C; Lumano-Mulenga P; Sikazwe I; Wyss N; Clough-Gorr KM; Egger M; Chi BH; Bohlius J; *Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland; †Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; ‡Division of Infectious Diseases, Department of Medicine, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; §Department of Pediatrics and Child Health, University of Stellenbosch and Tygerberg Academic Hospital, Cape Town, South Africa; ‖Khayelitsha ART Program, Medecins Sans Frontieres, Cape Town, South Africa; ¶Independent Surgery, Gaborone, Botswana; #Newlands Clinic, Harare, Zimbabwe; **Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia; ††Boston University School of Medicine, Section of Geriatrics, Boston, MA, USA; and ‡‡Centre for Infectious Disease Epidemiology and Research (CIDER), University of Cape Town, Cape Town, South Africa.
BACKGROUND: The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. METHODS: We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS: We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. Five hundred and sixty-four incident cases were diagnosed during 343,927 person-years (pys). The overall KS incidence rate was 164/100,000 pys [95% confidence interval (CI): 151 to 178]. The incidence rate was highest 30-90 days after ART initiation (413/100,000 pys; 95% CI: 342 to 497) and declined thereafter [86/100,000 pys (95% CI: 71 to 105), >2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (≥500 versus <50 cells/μL, adjusted HR: 0.36; 95% CI: 0.23 to 0.55), and age (5-9 years versus 30-39 years, adjusted HR: 0.20; 95% CI: 0.05 to 0.79) were relevant risk factors for developing KS. INTERPRETATION: Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality.
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.