Browsing by Author "Sinkala, Edford"

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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.
Care Continuum and Postdischarge Outcomes Among HIV-Infected Adults Admitted to the Hospital in Zambia.
(2019-Oct) Haachambwa, Lottie; Kandiwo, Nyakulira; Zulu, Paul M.; Rutagwera, David; Geng, Elvin; Holmes, Charles B.; Sinkala, Edford; Claassen, Cassidy W.; Mugavero, Michael J.; Wa Mwanza, Mwanza; Turan, Janet M.; Vinikoor, Michael J.
BACKGROUND: We characterized the extent of antiretroviral therapy (ART) experience and postdischarge mortality among hospitalized HIV-infected adults in Zambia. METHODS: At a central hospital with an opt-out HIV testing program, we enrolled HIV-infected adults (18+ years) admitted to internal medicine using a population-based sampling frame. Critically ill patients were excluded. Participants underwent a questionnaire regarding their HIV care history and CD4 count and viral load (VL) testing. We followed participants to 3 months after discharge. We analyzed prior awareness of HIV-positive status, antiretroviral therapy (ART) use, and VL suppression (VS; <1000 copies/mL). Using Cox proportional hazards regression, we assessed risk factors for mortality. RESULTS: Among 1283 adults, HIV status was available for 1132 (88.2%), and 762 (67.3%) were HIV-positive. In the 239 who enrolled, the median age was 36 years, 59.7% were women, and the median CD4 count was 183 cells/mm CONCLUSIONS: Most HIV-related hospitalizations and deaths may now occur among ART-experienced vs -naïve individuals in Zambia. Development and evaluation of inpatient interventions are needed to mitigate the high risk of death in the postdischarge period.
Chronic hepatitis B virus monoinfection at a university hospital in Zambia.
(2018-Sep-27) Vinikoor, Michael J.; Sinkala, Edford; Kanunga, Annie; Muchimba, Mutinta; Nsokolo, Bright; Chilengi, Roma; Wandeler, Gilles; Mulenga, Joseph; Chisenga, Tina; Bhattacharya, Debika; Saag, Michael S.; Foster, Graham; Fried, Michael W.; Kelly, Paul
AIM: To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia. METHODS: Hepatitis B surface antigen-positive adults ( RESULTS: The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified CONCLUSION: Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.
Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia.
(2015-Jul) Vinikoor, Michael J.; Sinkala, Edford; Mweemba, Aggrey; Zanolini, Arianna; Mulenga, Lloyd; Sikazwe, Izukanji; Fried, Micahel W.; Eron, Joseph J.; Wandeler, Gilles; Chi, Benjamin H.
BACKGROUND & AIMS: We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia. METHODS: Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunological status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. RESULTS: Among 20 308 adults in the analysis cohort, 1027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI <18, WHO clinical stage 3 or 4, CD4(+) count <200 cells/mm(3) , and tuberculosis. Among the 237 (1.2%) who were tested, HBsAg-positive patients had four times the odds (adjusted odds ratio, 4.15; 95% CI, 1.71-10.04) of significant fibrosis compared HBsAg-negatives. Both significant fibrosis (adjusted hazard ratio 1.41, 95% CI, 1.21-1.64) and cirrhosis (adjusted hazard ratio 1.57, 95% CI, 1.31-1.89) were associated with increased all-cause mortality. CONCLUSION: Liver fibrosis may be a risk factor for mortality during ART among HIV-infected individuals in Africa. APRI is an inexpensive and potentially useful test for liver fibrosis in resource-constrained settings.
Eligibility for hepatitis B antiviral therapy among adults in the general population in Zambia.
(2020) Vinikoor, Michael J.; Sinkala, Edford; Kanunga, Annie; Muchimba, Mutinta; Zanolini, Arianna; Saag, Michael; Pry, Jake; Nsokolo, Bright; Chisenga, Tina; Kelly, Paul
INTRODUCTION: We evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia. MATERIALS AND METHODS: Using a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines. RESULTS: Across 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99-1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81-0.98). Trends toward higher HBsAg-positivity were also seen at ages 30-39 years (AOR, 2.11; 95% CI, 0.96-4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93-3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART). CONCLUSION: Approximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.
Hepatitis B Therapy as HIV Prevention in Africa: A Case Series From Zambia.
(2019-Jan) Vinikoor, Michael J.; Sinkala, Edford; Chihota, Belinda; Kanunga, Annie; Wandeler, Gilles
Hepatosplenic schistosomiasis in Zambian adults is characterized by increased liver stiffness: A nested case-control study.
(2020-Jul) Sinkala, Edford; Vinikoor, Michael J.; Siyunda, Alice M.; Zyambo, Kanekwa; Besa, Ellen; Nsokolo, Bright; Wandeler, Gilles; Foster, Graham R.; Kelly, Paul
Cirrhosis commonly complicates portal hypertension worldwide but in Zambia hepatosplenic schistosomiasis (HSS) dominates as the cause of portal hypertension. We need easier and non-invasive ways to assess HSS. Transient elastography (TE), a measure of liver stiffness can diagnose liver cirrhosis. TE remains unexplored in HSS patients, who generally have normal liver parenchyma. We aimed to explore liver stiffness in HSS. This nested case control study was conducted at the University Teaching Hospital, Lusaka, Zambia between January 2015 and January 2016. We enrolled 48 adults with HSS and 22 healthy controls. We assessed liver stiffness using TE while plasma hyaluronan was used to assess liver fibrosis. Plasma tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) were used to assess inflammation. The median (interquartile range) liver stiffness was higher in patients, 9.5 kPa (7.8, 12.8) than in controls, 4.7 kPa (4.0, 5.4),
Impact of Antiretroviral Therapy on Liver Fibrosis Among Human Immunodeficiency Virus-Infected Adults With and Without HBV Coinfection in Zambia.
(2017-May-15) Vinikoor, 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.
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.
Propranolol Reduces Portal Vein Diameter in Schistosomal Liver Disease with Portal Hypertension: A Prospective Cohort Study.
(2020-Apr) Sinkala, Edford; Vinikoor, Michael J.; Zyambo, Kanekwa; Besa, Ellen; Nsokolo, Bright; Kelly, Paul
Hepatosplenic schistosomiasis (HSS) complicates portal hypertension, leading to life-threatening variceal bleeding. Variceal bleeding is associated with increased portal vein diameter (PVD). Beta-blockers prevent variceal bleeding. It is unclear whether beta-blockers such as propranolol can reduce PVD in HSS. We aimed to explore the effect of propranolol on PVD in HSS. A longitudinal study was conducted at the University Teaching Hospital, Zambia, as an extension of a clinical trial of rifaximin undertaken to test the hypothesis that rifaximin could reduce bacterial translocation in HSS. We randomized 85 adults to either rifaximin and standard care, or propranolol-based standard care only for 42 days. We then followed up all the patients on propranolol up to day 180. We used ultrasound to measure PVD at baseline and day 180. The primary outcome was reduction in PVD. Beta-blockade and splenic size reduction were secondary outcomes. Portal vein diameter reduced after 180 days of propranolol therapy from median 12 mm (interquartile range (IQR): 11-14) to median 10 mm (IQR: 9-13) (
Response to 'Is AST-to-platelet ratio index a reliable tool in HIV patients in Africa?'.
(2015-Aug) Vinikoor, Michael J.; Sinkala, Edford; Wandeler, Gilles; Chi, Benjamin H.
Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.
(2018-Apr) Sinkala, Edford; Zyambo, Kanekwa; Besa, Ellen; Kaonga, Patrick; Nsokolo, Bright; Kayamba, Violet; Vinikoor, Michael J.; Zulu, Rabison; Bwalya, Martin; Foster, Graham R.; Kelly, Paul
Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196),