Browsing by Author "Wandeler G"

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A new approach to prevent, diagnose, and treat hepatitis B in Africa.
(2023) Spearman CW; Andersson MI; Bright B; Davwar PM; Desalegn H; Guingane AN; Johannessen A; Kabagambe K; Lemoine M; Matthews PC; Ndow G; Riches N; Shimakawa Y; Sombié R; Stockdale AJ; Taljaard JJ; Vinikoor MJ; Wandeler G; Okeke E; Sonderup M
There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.
Alcohol reduction outcomes following brief counseling among adults with HIV in Zambia: A sequential mixed methods study.
(2022) Asombang M; Helova A; Chipungu J; Sharma A; Wandeler G; Kane JC; Turan JM; Smith H; Vinikoor MJ
Data from sub-Saharan Africa on the impact of alcohol on the HIV epidemic in sub-Saharan Africa is limited. In this region, it is not well understood how people with HIV (PLWHA) respond to alcohol reduction counseling while they are linked to HIV clinical care. We conducted an explanatory sequential mixed-methods study to understand patterns of alcohol use among adults (18+ years) within a prospective HIV cohort at two urban public-sector clinics in Zambia. At antiretroviral therapy (ART) start and one year later, we measured alcohol use with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and those reporting any alcohol use were provided brief counseling. We conducted focus groups at 1 year with participants who had any alcohol use and 20 in-depth interviews among the subgroup with unhealthy use pre-ART and who either reduced or did not reduce their use by 1 year to moderate levels or abstinence. Focus group Discussions (FGDs) (n = 2) were also held with HIV clinic staff. Qualitative data were analyzed using thematic analysis. The data obtained from 693 participants was analyzed (median age 34 years, 45% men), it revealed that unhealthy alcohol use (AUDIT-C >3 for men; >2 for women) was reported among 280 (40.4%) at baseline and 205 (29.6%) at 1 year on ART. Reduction from unhealthy to moderate use or abstinence was more common with older age, female, non-smoking, and at Clinic B (all P<0.05). Qualitative data revealed ineffective alcohol support at clinics, social pressures in the community to consume alcohol, and unaddressed drivers of alcohol use including poverty, poor health status, depression, and HIV stigma. Healthcare workers reported a lack of training in alcohol screening and treatment, which led to mixed messages provided to patients ('reduce to safe levels' versus 'abstain'). In summary, interventions to reduce unhealthy alcohol use are needed within HIV clinics in Zambia as a substantial population have persistent unhealthy use despite current HIV clinical care. A better understanding is needed regarding the implementation challenges related to screening for unhealthy alcohol use integrated with HIV services.
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
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.
Diagnostic value of serological scores for the detection of liver steatosis in people with HIV in low- and middle-income countries.
(2026-May-01) Plaisy MK; Mondoka C; Moreira R; Samala N; Borse R; Kuniholm MH; Minga A; Wandeler G; Lopez-Iñiguez A; Michael D; Ross J; Shumbusho F; Mensah E; Shamu T; Crabtree-Ramirez BE; Byakwaga H; Rupasinghe D; Murenzi G; Mureithi F; Diero L; Mivumbi JP; Nguyen DTH; Maruri F; Jaquet A; Perazzo H
BACKGROUND: The accuracy of Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) to predict liver steatosis in people with HIV (PWH) remains poorly studied in low- and middle-income countries (LMICs). We assessed their diagnostic performances in a multiregional cohort. METHODS: This cross-sectional analysis included PWH aged ≥40 years on antiretroviral therapy for ≥6 months at enrolment (2020-2023) in the Sentinel Research Network (SRN) of IeDEA consortium, across 12 HIV clinics in Asia-Pacific, Americas, and central, East, southern, and West Africa regions. Liver steatosis was defined based on Controlled Attenuation Parameter (CAP) ≥248 dB/m using vibration-controlled transient elastography. HSI was evaluated in the overall population, while FLI was assessed and compared to HSI in a subset of participants with available data. Model discrimination was assessed using area under the receiver operating characteristic curve (AUROC) and model calibration with calibration plots. A decision curve analysis was performed to compare their clinical utility. RESULTS: Among 2195 PWH assessed using CAP, 624 (28.4%) presented with liver steatosis. HSI showed acceptable discriminative ability (AUROC = 0.74) but poor calibration, generally overestimating the risk, except in Asia-Pacific region. FLI performed better than HSI (AUROC = 0.80, P < 0.001), and demonstrated good calibration except in sub-Saharan Africa. Both scores showed high clinical utility, with FLI demonstrating a greater net benefit when compared with HSI. CONCLUSION: FLI demonstrated higher accuracy and clinical utility within a subgroup of regions. However, the limited performance of FLI and HSI in sub-Saharan populations highlights the need to adapt existing tools or develop new predictive models tailored to regional contexts.
Elimination of Viral Hepatitis in Low and Middle-Income Countries: Epidemiological Research Gaps.
(2021-Sep) Jaquet A; Muula G; Ekouevi DK; Wandeler G
PURPOSE OF REVIEW: The purpose of our review was to summarize current recommendations on testing strategies, antiviral therapy eligibility and monitoring, and prevention of mother-to-child transmission of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and to highlight major research gaps in low and middle-income countries (LMIC), with a particular focus on sub-Saharan Africa (SSA). RECENT FINDINGS: While data on the prevalence of HBV and HCV infections in LMIC are increasing, current knowledge on liver-related complications as well as on treatment outcomes remains limited. Furthermore, very little information is available on the feasibility and cost-effectiveness of large-scale testing and management strategies in high-prevalence settings. The availability of policy-relevant data is particularly scarce in SSA, which accounts for a significant part of the global burden of chronic viral hepatitis. SUMMARY: Current recommendations on the management and monitoring of chronic viral hepatitis rely mainly on data from high-income settings. The global elimination of viral hepatitis will only be achieved if prevention, testing, and treatment strategies tailored to specific LMIC are implemented. In order to inform scalable and cost-effective interventions, dedicated research initiatives have to be undertaken. Future studies will have to include the evaluation of innovative testing strategies, the validation of simplified methods to diagnose liver cirrhosis and hepatocellular carcinoma, and the monitoring of long-term treatment outcomes and toxicity. In addition, national plans to achieve the elimination of HBV mother-to-child transmission are urgently needed, including effective ways to test pregnant women, treat those who are eligible, and ensure birth dose vaccination is given to all newborns.
Hepatitis B and C Prevention, Screening and Diagnostic Services at HIV Treatment Sites: International epidemiology Databases to Evaluate AIDS.
(2026-May-05) Kuniholm MH; Murenzi G; Samala N; Yunihastuti E; Wandeler G; Kim HN; Plaisy MK; Perazzo H; Twizere C; Odhiambo F; Bopage R; Muula G; Lo Re V; Minga A; López-Iñiguez A; Nsonde DM; Kasozi C; Wati DK; Fox MP; Kirk GD; Messou E; Cesar C; Ebasone PV; Byakwaga H; Ross J; Chimbetete C; Yendewa GA; Jaquet A; Succi RCM; Maruri F; Brazier E
BACKGROUND: Prevention, screening and diagnostic services for hepatitis B virus (HBV) and hepatitis C virus (HCV) can prevent morbidity and mortality in people receiving HIV care. However, there is limited information about the availability of HBV and HCV services at HIV clinics globally. METHODS: The International epidemiology Databases to Evaluate AIDS (IeDEA) conducted surveys of service delivery and practices at participating HIV treatment centers from seven regions. We used 2023 survey data to measure availability of HBV vaccination, HBV and HCV screening, HBV surface antigen (HBsAg), HBV DNA, HCV antibody, HCV RNA testing. Multivariable logistic regression models were used to test associations of site characteristics with HBV and HCV services. RESULTS: HBV vaccination was available on-site at 67.7% of 204 HIV treatment sites. Screening for HBV and HCV at HIV care enrollment was reported by 72.1% and 50% of sites, respectively. HBsAg, HBV DNA, HCV antibody and HCV RNA testing were available on-site at 77%, 47.6%, 61.8% and 44.6% of sites, respectively. Sites serving predominately rural (vs. urban) populations were less likely to report on-site availability of HBV DNA (odds ratio (OR):0.07; 95% confidence interval (CI):0.01-0.68;P=0.02), HCV antibody (OR=0.18; 95% CI:0.04-0.92;P=0.04) and HCV RNA (OR=0.10; 95% CI:0.01-0.90;P=0.04) testing. CONCLUSION: Life-saving services such as HBV vaccination, HBsAg and HCV antibody testing were available on-site at most HIV treatment sites participating in the IeDEA network. Lower availability at rural sites suggests that expansion of services is important to eliminate HBV and HCV as public health problems in people receiving HIV care.
Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia.
(2023-Nov-01) Muula GK; Bosomprah S; Sinkala E; Nsokolo B; Musonda T; Hamusonde K; Bhattacharya D; Lauer G; Chung RT; Mulenga LB; Wandeler G; Vinikoor MJ
BACKGROUND: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. METHODS: In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers. RESULTS: Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/μl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/μl. HIV was not associated with markers of fibrosis or ALT. DISCUSSION: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.
Implementation of routine screening for chronic hepatitis B virus co-infection by HIV clinics in Lusaka, Zambia.
(2015-Oct) Vinikoor MJ; Musukuma K; Munamunungu V; Masaninga M; Sikazwe I; Chi BH; Wandeler G
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
INTRODUCTION: The growing importance of non-communicable diseases (NCDs) and high HIV prevalence in urban African settings may increase the burden of metabolic dysfunction-associated fatty liver disease (MAFLD). We assessed liver steatosis among HIV-positive and negative adults in urban Zambia. METHODS: Adults 30 years and older who were newly diagnosed with HIV, or tested HIV-negative at two primary care clinics in Lusaka, Zambia, were assessed for liver steatosis. Cardiometabolic data were collected through comprehensive clinical and laboratory assessments. Transient elastography was performed to measure controlled-attenuation parameter (≥248 dB/m). We used multivariable logistic regression models to determine the factors associated with the presence of steatosis. RESULTS: We enrolled 381 patients, including 154 (40%) antiretroviral therapy-naïve people living with HIV (PLWH) with a median CD4+ count of 247 cells/mm CONCLUSIONS: The prevalence of liver steatosis in this urban cohort of HIV-positive and negative adults in Zambia was low, despite a large proportion of patients with high BMI and central obesity. Our study is among the first to report data on MAFLD among adults in Africa, demonstrating that metabolic risk factors are key drivers of liver steatosis and supporting the adoption of the criteria for MAFLD in African populations.
Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.
(2024-Jun-14) Vinikoor MJ; Hamusonde K; Muula G; Asombang M; Riebensahm C; Chitundu H; Sunkuntu-Sichizya V; Bhattacharya D; Sinkala E; Lauer G; Chung R; Mbewe W; Egger M; Bosomprah S; Wandeler G
BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. CONCLUSIONS: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.
New Window Into Hepatitis B in Africa: Liver Sampling Combined With Single-Cell Omics Enables Deep and Longitudinal Assessment of Intrahepatic Immunity in Zambia.
(2024-Nov-15) Musonda T; Wallace MS; Patel H; Martin OP; Oetheimer C; Mwakamui S; Sinkala E; Nsokolo B; Kanunga A; Lauer G; Chung RT; Wandeler G; Bhattacharya D; Kelly P; Alatrakchi N; Vinikoor MJ
In Lusaka, Zambia, we introduced liver fine-needle aspiration biopsy (FNAB) into a research cohort of adults with treatment-naive chronic hepatitis B virus (HBV) infection, with and without human immunodeficiency virus (HIV) coinfection, as well as with acute HBV infection. From 117 enrollment and 47 longitudinal FNABs (at 1-year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single-cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.
Screening for hepatocellular carcinoma among adults with HIV/HBV co-infection in Zambia: a pilot study.
(2022-Mar) Riebensahm C; Chitundu H; Muula G; Chihota B; Sinkala E; Sunkutu V; Maurer MH; Dufour JF; Berzigotti A; Egger M; Bolton-Moore C; Vinikoor M; Wandeler G
BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). An HCC screening initiative was piloted in an established cohort of individuals co-infected with human immunodeficiency virus (HIV) and HBV on antiretroviral therapy (ART) at two outpatient clinics in Lusaka, Zambia. METHODS: All patients underwent abdominal ultrasound (AUS) and transient elastography. RESULTS: Among 279 patients co-infected with HIV/HBV, 165 (59.1%) were men, median age was 34 years [interquartile range (IQR) 28-39 years] and median CD4 count was 246 cells/µL (IQR 112-355 cells/µL) at ART initiation. While 102 (55.7%) individuals had elevated transaminases, 114 (59.7%) had HBV levels >2000 IU/mL and 59 (24.6%) had significant fibrosis. At their first AUS measurement, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) had periportal fibrosis. Five patients had a liver lesion >1 cm, an indication for confirmatory imaging. CONCLUSIONS: In one of the first HCC screening initiatives in SSA, 2% of patients co-infected with HIV/HBV had significant liver lesions, and one-quarter had findings suggestive of schistosomiasis-induced liver damage.
The Social Construction of Aging Among a Clinic-Based Population and Their Healthcare Workers in Zambia.
(2024) Sharma A; Mwamba C; St Clair-Sullivan N; Chihota BV; Pry JM; Bolton-Moore C; Vinikoor MJ; Muula GK; Daultrey H; Gittelsohn J; Mulenga LB; Siyumbwa N; Wandeler G; Vera JH
OBJECTIVES: We sought to understand the social construction of aging in a clinic-based population, with and without HIV, to address gaps in care for older individuals living with HIV in Zambia. METHODS: Our exploratory qualitative study included 36 in-depth interviews with clinic clients and four focus group discussions with 36 professional and lay healthcare workers providing services to the clients. We identified themes based on social construction theory. RESULTS: At the individual level, aging was multidimensional, perceived both as an achievement in the HIV era and as a period of cognitive, physical, and economic decline. In social interactions, older individuals were often stereotyped and treated as helpless, poor, and "witches." Those living with HIV faced the additional stigma of being labeled as promiscuous. Some of the participants living without HIV refused to take daily medication for non-communicable diseases to avoid being mistaken for taking antiretroviral therapy for HIV. Older individuals wanted quality healthcare and family support to address the intersectional stigma of aging, poverty, and chronic illness. CONCLUSION: Multifaceted interventions are required to combat age-related prejudice, intersectional stigma, and discriminatory practices, particularly for people living with HIV.