Browsing by Author "Egger, Matthias"

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Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique.
(2016-Mar) Wandeler, Gilles; Mulenga, Lloyd; Hobbins, Michael; Joao, Candido; Sinkala, Edford; Hector, Jonas; Aly, Musa; Chi, Benjamin H.; Egger, Matthias; Vinikoor, Michael J.
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.
Authors' Reply: Early Initiation of Antiretroviral Therapy Among Young Children: A Long Way to Go.
(2015-Oct-01) Koller, Manuel; Patel, Kunjal; Chi, Benjamin H.; Wools-Kaloustian, Kara; Dicko, Fatoumata; Chokephaibulkit, Kulkanya; Chimbetete, Cleophas; Hazra, Rohan; Ayaya, Samuel; Leroy, Valeriane; Trong, Huu K.; Egger, Matthias; Davies, Mary-Ann
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, Sophie; Wa Mwanza, Mwanza; Chilengi, Roma; Holmes, Charles B.; Zyambo, Zude; Furrer, Hansjakob; Egger, Matthias; Wandeler, Gilles; Vinikoor, Michael J.
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, Daryoush; Muula, Guy; Banholzer, Nicolas; Chibomba, Douglas; Xulu, Sihle ; Bolton, Carolyn; Evans, Denise; Perrig, Lisa; De Marchi, Stefano ; Günther, Gunar; Egger, Matthias; Pilgrim, Thomas; Fenner, Lukas
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, Patience; Schomaker, Michael ; Boulle, Andrew ; Euvrard, Jonathan; Wood, Robin ; Eley, Brian; Prozesky, Hans; Christ, Benedikt; Anderegg, Nanina; Ayakaka, Irene; Rafael, Idiovino ; Kunzekwenyika, Cordelia; Moore, Carolyn B.; Lettow, Monique van ; Chimbetete, Cleophas ; Mbewe, Safari; Ballif, Marie; Egger, Matthias; Yiannoutsos, Constantin T.; Cornell, Morna; Davies, Mary-Ann
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.
Drug Resistance in People With Viremia on Dolutegravir-based Antiretroviral Therapy in Sub-Saharan Africa: The DTG RESIST Study.
(2025-May-20) Loosli, Tom; Bolton-Moore, Carolyn; Buzaalirwa, Lydia; Byakwaga, Helen; Çelikağ, İpek; Chimbetete, Cleophas; Ebasone, Peter V.; Giandhari, Jennifer; Han, Nuri; Huwa, Jacqueline; Kasozi, Charles; Mafoua, Adolphe; Messou, Eugène ; Minga, Albert; Muula, Guy; Muyindike, Winnie; Ndala, Arcel C. M.; Sauermann, Mamatha ; Semeere, Aggrey; Singh, Lavanya; Kouyos, Roger D.; Lessells, Richard; Egger, Matthias
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, Andreas D.; Johnson, Leigh F.; Grimsrud, Anna; Ford, Nathan; Mugglin, Catarina; Fox, Matthew P.; Euvrard, Jonathan; van Lettow, Monique; Prozesky, Hans; Sikazwe, Izukanji; Chimbetete, Cleophas; Hobbins, Michael; Kunzekwenyika, Cordelia; Egger, Matthias
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, Tiana C.; Joseph, Lavania; Moono, Andrew; Göller, Pauline C.; Motsei, Mamello; Muula, Guy; Evans, Denise; Neuenschwander, Stefan; Günther, Gunar; Bolton, Carolyn; Keller, Peter M.; Ramette, Alban; Egger, Matthias; Omar, Shaheed V.; Fenner, Lukas
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, Gilles; Musukuma, Kalo; Zürcher, Samuel; Vinikoor, Michael J.; Llenas-García, Jara; Aly, Mussa M.; Mulenga, Lloyd; Chi, Benjamin H.; Ehmer, Jochen; Hobbins, Michael A.; Bolton-Moore, Carolyn; Hoffmann, Christopher J.; Egger, Matthias
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, Marcellin N.; Vinikoor, Michael J.; Seydi, Moussa; Ekouevi, Didier K.; Coffie, Patrick A.; Mulenga, Lloyd; Tanon, Aristophane; Egger, Matthias; Dabis, Francois; Jaquet, Antoine; Wandeler, Gilles
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.
Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.
(2015-Jan-01) Koller, Manuel; Patel, Kunjal; Chi, Benjamin H.; Wools-Kaloustian, Kara; Dicko, Fatoumata; Chokephaibulkit, Kulkanya; Chimbetete, Cleophas; Avila, Dorita; Hazra, Rohan; Ayaya, Samual ; Leroy, Valeriane; Truong, Huu K.; Egger, Matthias; Davies, Mary-Ann
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, Michael J.; Sinkala, Edford; Chilengi, Roma; Mulenga, Lloyd B.; Chi, Benjamin H.; Zyambo, Zude; Hoffmann, Christopher J.; Saag, Michael S.; Davies, Mary-Ann; Egger, Matthias ; Wandeler, Gilles
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, Manuel; Fatti, Geoffrey; Chi, Benjamin H.; Keiser, Olivia; Hoffmann, Christopher J.; Wood, Robin; Prozesky, Hans; Stinson, Kathryn; Giddy, Janet; Mutevedzi, Portia; Fox, Matthew P.; Law, Matthew; Boulle, Andrew; Egger, Matthias
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, Eliane; Valeri, Fabio; Maskew, Mhairi; Prozesky, Hans; Rabie, Helena; Garone, Daniela; Dickinson, Diana; Chimbetete, Cleophas; Lumano-Mulenga, Priscilla; Sikazwe, Izukanji; Wyss, Natascha; Clough-Gorr, Kerri M.; Egger, Matthias; Chi, Benjamin H.; Bohlius, Julia
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, Gilles; Mulenga, Lloyd; Vinikoor, Michael J.; Kovari, Helen; Battegay, Manuel; Calmy, Alexandra; Cavassini, Matthias; Bernasconi, Enos; Schmid, Patrick; Bolton-Moore, Carolyn; Sinkala, Edford; Chi, Benjamin H.; Egger, Matthias; Rauch, Andri
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.
Mental, physical, and respiratory health in people with tuberculosis in Southern Africa: a multi-country cohort analysis.
(2025-Aug-20) Banholzer, Nicolas; Muula, Guy; Mureithi, Fiona; Evans, Denise; Huwa, Jacqueline; Rafael, Idiovino ; Kunzekwenyika, Cordelia; Jinga, Nelly; Fernando, Amina; Thawani, Agness; Schmutz, Remo; Bolton, Carolyn; Günther, Gunar; Egger, Matthias ; Haas, Andreas D.; Sweetland, Annika C.; Ballif, Marie; Fenner, Lukas
BACKGROUND: Tuberculosis (TB) affects people's quality of life (QoL). We prospectively monitored physical and mental health-related QoL over time in people with TB in the Southern African region with a high HIV and TB burden. METHODS: Adults aged ≥ 15 years with pulmonary TB were enrolled in five cohorts in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe from October 2022 to September 2024. We assessed six QoL outcomes using validated instruments at the start (baseline), end of treatment, and 6 months post-treatment: symptoms of depression (PHQ-9), mental and physical health (SF-12 mental, SF12-MC, SF-12 physical component, SF12-PC), physical fitness (6-Minute Walk Test, 6MWT; 1-min Sit-To-Stand Test, STST), and respiratory health (Saint-George-Respiratory-Questionnaire, SGRQ). Missing QoL scores were imputed with multivariate imputation by chained equations. We compared the proportion of participants with impaired QoL, defining impairment based on outcome-specific cut-off values. We also estimated changes in QoL scores and examined their associations with baseline characteristics using Bayesian multivariable regression models. RESULTS: We included 1438 participants with a median follow-up of 344 days (interquartile range [IQR] 183-373). The median age was 39 years (IQR 30-50); 67% were male, and 39% living with HIV. At baseline, 49% had symptoms of depression, 73% had impaired mental health and 92% impaired physical health-related QoL, 68-74% had reduced physical fitness (68%: 6MWT, 74%: STST), and 78% impaired respiratory health. All QoL outcomes improved by the end of treatment, notably depressive symptoms (48% to 5%), mental health-related QoL (73% to 28%), and respiratory health (78% to 11%). Most QoL impairments continued to decrease post-treatment, especially physical and respiratory health; depressive symptoms remained below 5%. Across QoL domains and study visits, better outcomes were associated with age < 30 (83% probability), and worse outcomes with female gender (86%) and a prior TB history (89%). Living with HIV and alcohol drinking were associated with worse QoL only at baseline (88% and 87%). CONCLUSIONS: TB negatively impacts QoL across physical, mental, and social domains, including post-treatment. The study highlights the need for integrated mental and physical healthcare and rehabilitation during TB treatment and beyond, especially for high-risk populations, to address the long-term impact of TB on QoL.
Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis.
(2015-Jul) Haas, Andreas D.; Keiser, Olivia; Balestre, Eric; Brown, Steve; Bissagnene, Emmanuel; Chimbetete, Cleophas; Dabis, François; Davies, Mary-Ann; Hoffmann, Christopher J.; Oyaro, Patrick; Parkes-Ratanshi, Rosalind; Reynolds, Steven J.; Sikazwe, Izukanji; Wools-Kaloustian, Kara; Zannou, Marcel D.; Wandeler, Gilles; Egger, Matthias
BACKGROUND: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa. METHODS: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics. FINDINGS: Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL). INTERPRETATION: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing. FUNDING: National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.
No Impact of Hepatitis B Virus Infection on Early Mortality Among Human Immunodeficiency Virus-Infected Patients in Southern Africa.
(2018-Sep-28) Hector, Jonas; Vinikoor, Michael J.; Chilengi, Roma; Ehmer, Jochen; Egger, Matthias; Wandeler, Gilles
Prognosis of children with HIV-1 infection starting antiretroviral therapy in Southern Africa: a collaborative analysis of treatment programs.
(2014-Jun) Davies, Mary-Anne; May, Margaret; Bolton-Moore, Carolyn; Chimbetete, Cleophas; Eley, Brian; Garone, Daniela; Giddy, Janet; Moultrie, Harry; Ndirangu, James; Phiri, Sam; Rabie, Helena; Technau, Karl-Günter ; Wood, Robin; Boulle, Andrew; Egger, Matthias; Keiser, Olivia
BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years of age who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004 to 2010. Children lost to follow up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct 2 prognostic models: 1 with CD4%, age, World Health Organization clinical stage, weight-for-age z-score (WAZ) and anemia and the other without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12,655 children, 877 (6.9%) died in the first year of ART. We excluded 1780 children who were lost to follow up/transferred from main analyses; 10,875 children were therefore included. With the CD4% model probability of death at 1 year ranged from 1.8% [95% confidence interval (CI): 1.5-2.3] in children 5-10 years with CD4% ≥10%, World Health Organization stage I/II, WAZ ≥ -2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% < 5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics = 0.753 and 0.745 for models with and without CD4%, respectively). CONCLUSIONS: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.
Retention and mortality on antiretroviral therapy in sub-Saharan Africa: collaborative analyses of HIV treatment programmes.
(2018-Feb) Haas, Andreas D.; Zaniewski, Elizabeth; Anderegg, Nanina; Ford, Nathan; Fox, Matthew P.; Vinikoor, Michael J.; Dabis, François; Nash, Denis; Sinayobye, Jean D.; Niyongabo, Thêodore; Tanon, Aristophane; Poda, Armel; Adedimeji, Adebola A.; Edmonds, Andrew; Davies, Mary-Ann; Egger, Matthias
INTRODUCTION: By 2020, 90% of all people diagnosed with HIV should receive long-term combination antiretroviral therapy (ART). In sub-Saharan Africa, this target is threatened by loss to follow-up in ART programmes. The proportion of people retained on ART long-term cannot be easily determined, because individuals classified as lost to follow-up, may have self-transferred to another HIV treatment programme, or may have died. We describe retention on ART in sub-Saharan Africa, first based on observed data as recorded in the clinic databases, and second adjusted for undocumented deaths and self-transfers. METHODS: We analysed data from HIV-infected adults and children initiating ART between 2009 and 2014 at a sub-Saharan African HIV treatment programme participating in the International epidemiology Databases to Evaluate AIDS (IeDEA). We used the Kaplan-Meier method to calculate the cumulative incidence of retention on ART and the Aalen-Johansen method to calculate the cumulative incidences of death, loss to follow-up, and stopping ART. We used inverse probability weighting to adjust clinic data for undocumented mortality and self-transfer, based on estimates from a recent systematic review and meta-analysis. RESULTS: We included 505,634 patients: 12,848 (2.5%) from Central Africa, 109,233 (21.6%) from East Africa, 347,343 (68.7%) from Southern Africa and 36,210 (7.2%) from West Africa. In crude analyses of observed clinic data, 52.1% of patients were retained on ART, 41.8% were lost to follow-up and 6.0% had died 5 years after ART initiation. After accounting for undocumented deaths and self-transfers, we estimated that 66.6% of patients were retained on ART, 18.8% had stopped ART and 14.7% had died at 5 years. CONCLUSIONS: Improving long-term retention on ART will be crucial to attaining the 90% on ART target. Naïve analyses of HIV cohort studies, which do not account for undocumented mortality and self-transfer of patients, may severely underestimate both mortality and retention on ART.