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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02344680
Other study ID # F150819001
Secondary ID 1K01TW009998
Status Active, not recruiting
Phase
First received
Last updated
Start date October 2015
Est. completion date August 2024

Study information

Verified date June 2023
Source University of Alabama at Birmingham
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

In this study the investigators will determine risk factors for liver fibrosis among HIV-HBV co-infected patients in Lusaka, Zambia, and assess the long-term effectiveness of antiretroviral drugs in the prevention and/or reduction of liver disease.


Description:

Among HIV-infected individuals in Africa, liver disease is a neglected area of investigation but is anticipated to become increasingly common as patients live longer due to antiretroviral therapy. In a currently approved and active research study taking place in Lusaka Urban district - HIV/HBV co-infection in IeDEA-SA (NCT02060162, clinicaltrials.gov) - 800 consecutive HIV-infected adults were screened for possible causes of liver disease and 12% were diagnosed with chronic hepatitis B virus (HBV) co-infection. HBV co-infected patients were more likely to have evidence of liver disease; however, ascertainment of critical long-term outcomes of HIV-HBV patients was not part of the study. Building on these preliminary results and addressing the need to study HIV-HBV during a longer duration of follow-up, the current protocol will focus exclusively on Zambian HIV-HBV patients. In the proposed study, the investigators will determine the risk factors for liver disease among Zambian HIV-HBV co-infected patients, and assess the long-term effectiveness of Ministry of Health (MOH)-recommended antiretroviral drugs in the prevention and/or reduction of HIV-HBV liver disease. This study will provide useful clinical and epidemiologic information to health policymakers in Zambia and throughout the region and may lead to improvements in the care of HIV-HBV patients. Further, it will strengthen collaboration between Zambian institutions and strengthen local capacity in HBV diagnosis and management.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 303
Est. completion date August 2024
Est. primary completion date August 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age 18 years or older - HIV-infected - HBV-infected, defined as any single positive HBsAg assay - Naïve to antiretroviral therapy or currently participating in HIV/HBV co-infection in IeDEA-SA Exclusion Criteria: - Unable or unwilling to provide informed consent - Planning to relocate out of Lusaka district

Study Design


Intervention

Drug:
Anti-HIV Agents


Locations

Country Name City State
Zambia Centre for Infectious Disease Research in Zambia (CIDRZ) Lusaka

Sponsors (3)

Lead Sponsor Collaborator
University of Alabama at Birmingham Fogarty International Center of the National Institute of Health, National Institutes of Health (NIH)

Country where clinical trial is conducted

Zambia, 

References & Publications (36)

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Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva: World Health Organization; 2013 Jun. Available from http://www.ncbi.nlm.nih.gov/books/NBK195400/ — View Citation

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Kapembwa KC, Goldman JD, Lakhi S, Banda Y, Bowa K, Vermund SH, Mulenga J, Chama D, Chi BH. HIV, Hepatitis B, and Hepatitis C in Zambia. J Glob Infect Dis. 2011 Jul;3(3):269-74. doi: 10.4103/0974-777X.83534. — View Citation

Kelly P, Saloojee H, Chen JY, Chung RT. Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects. J Acquir Immune Defic Syndr. 2014 Sep 1;67 Suppl 1(0 1):S79-86. doi: 10.1097/QAI.0000000000000260. — View Citation

Kim BK, Fung J, Yuen MF, Kim SU. Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives. World J Gastroenterol. 2013 Mar 28;19(12):1890-900. doi: 10.3748/wjg.v19.i12.1890. — View Citation

Kirk GD, Bah E, Montesano R. Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia, West Africa. Carcinogenesis. 2006 Oct;27(10):2070-82. doi: 10.1093/carcin/bgl060. Epub 2006 May 5. Erratum In: Carcinogenesis. 2006 Dec;27(12):2565. — View Citation

Lok AS. Chronic hepatitis B. N Engl J Med. 2002 May 30;346(22):1682-3. doi: 10.1056/NEJM200205303462202. No abstract available. — View Citation

Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Aguilar Schall R, Bornstein JD, Kitrinos KM, Subramanian GM, McHutchison JG, Heathcote EJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013 Feb 9;381(9865):468-75. doi: 10.1016/S0140-6736(12)61425-1. Epub 2012 Dec 10. — View Citation

Martin-Carbonero L, Teixeira T, Poveda E, Plaza Z, Vispo E, Gonzalez-Lahoz J, Soriano V. Clinical and virological outcomes in HIV-infected patients with chronic hepatitis B on long-term nucleos(t)ide analogues. AIDS. 2011 Jan 2;25(1):73-9. doi: 10.1097/QAD.0b013e328340fde2. — View Citation

Miailhes P, Pradat P, Chevallier M, Lacombe K, Bailly F, Cotte L, Trabaud MA, Boibieux A, Bottero J, Trepo C, Zoulim F. Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients. J Viral Hepat. 2011 Jan;18(1):61-9. doi: 10.1111/j.1365-2893.2010.01275.x. — View Citation

Puoti M, Manno D, Nasta P, Carosi G. Hepatitis B virus and HIV coinfection in low-income countries: unmet needs. Clin Infect Dis. 2008 Feb 1;46(3):367-9. doi: 10.1086/525532. No abstract available. — View Citation

Puoti M, Torti C, Bruno R, Filice G, Carosi G. Natural history of chronic hepatitis B in co-infected patients. J Hepatol. 2006;44(1 Suppl):S65-70. doi: 10.1016/j.jhep.2005.11.015. Epub 2005 Nov 28. — View Citation

Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003 Dec;29(12):1705-13. doi: 10.1016/j.ultrasmedbio.2003.07.001. — View Citation

Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791-804. doi: 10.1111/j.1360-0443.1993.tb02093.x. — View Citation

Stabinski L, Reynolds SJ, Ocama P, Laeyendecker O, Ndyanabo A, Kiggundu V, Boaz I, Gray RH, Wawer M, Thio C, Thomas DL, Quinn TC, Kirk GD; Rakai Health Sciences Program. High prevalence of liver fibrosis associated with HIV infection: a study in rural Rakai, Uganda. Antivir Ther. 2011;16(3):405-11. doi: 10.3851/IMP1783. — View Citation

Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317-25. doi: 10.1002/hep.21178. — View Citation

The Zambian National Health Research Bill, 2013

Thio CL, Seaberg EC, Skolasky R Jr, Phair J, Visscher B, Munoz A, Thomas DL; Multicenter AIDS Cohort Study. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002 Dec 14;360(9349):1921-6. doi: 10.1016/s0140-6736(02)11913-1. — View Citation

Thio CL. Hepatitis B in the human immunodeficiency virus-infected patient: epidemiology, natural history, and treatment. Semin Liver Dis. 2003 May;23(2):125-36. doi: 10.1055/s-2003-39951. — View Citation

Tuma P, Medrano J, Resino S, Vispo E, Madejon A, Sanchez-Piedra C, Rivas P, Labarga P, Martin-Carbonero L, Barreiro P, Soriano V. Incidence of liver cirrhosis in HIV-infected patients with chronic hepatitis B or C in the era of highly active antiretroviral therapy. Antivir Ther. 2010;15(6):881-6. doi: 10.3851/IMP1630. — View Citation

Vinikoor MJ, Schuttner L, Moyo C, Li M, Musonda P, Hachaambwa LM, Stringer JS, Chi BH. Short communication: Late refills during the first year of antiretroviral therapy predict mortality and program failure among HIV-infected adults in urban Zambia. AIDS Res Hum Retroviruses. 2014 Jan;30(1):74-7. doi: 10.1089/AID.2013.0167. Epub 2013 Aug 30. — View Citation

Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003 Aug;38(2):518-26. doi: 10.1053/jhep.2003.50346. — View Citation

Wandeler G, Gsponer T, Bihl F, Bernasconi E, Cavassini M, Kovari H, Schmid P, Battegay M, Calmy A, Egger M, Furrer H, Rauch A; Swiss HIV Cohort Study. Hepatitis B virus infection is associated with impaired immunological recovery during antiretroviral therapy in the Swiss HIV cohort study. J Infect Dis. 2013 Nov 1;208(9):1454-8. doi: 10.1093/infdis/jit351. Epub 2013 Jul 30. — View Citation

Weber R, Sabin CA, Friis-Moller N, Reiss P, El-Sadr WM, Kirk O, Dabis F, Law MG, Pradier C, De Wit S, Akerlund B, Calvo G, Monforte Ad, Rickenbach M, Ledergerber B, Phillips AN, Lundgren JD. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006 Aug 14-28;166(15):1632-41. doi: 10.1001/archinte.166.15.1632. — View Citation

Zambian Ministry of Health. Guidelines for the care of individuals with HIV/AIDS, 2010.

* Note: There are 36 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Change in liver fibrosis stage Measure of liver fibrosis using AST-to-platelet ratio index (APRI), Fibrosis 4 (FIB-4) and transient elastography. Ascertainment of potential risk factors including demographics, alcohol use, HIV-related biomarkers, HBV DNA, hepatitis delta virus, and other factors. From baseline to month 48
Secondary Incidence of hepatocellular carcinoma Liver cancer screening at baseline and during follow-up From baseline to month 48
Secondary Prevalence of significant liver fibrosis (Metavir F2 or greater) Measure of liver fibrosis using AST-to-platelet ratio index (APRI), Fibrosis 4 (FIB-4) and transient elastography At enrollment
Secondary Risk factors for persistent HBV viremia 9Measure HBV DNA at baseline and month 12 and determine patient characteristics associated with unsuppressed HBV after 12 months of treatment) Measure HBV DNA at baseline and month 12 and determine patient characteristics associated with unsuppressed HBV after 12 months of treatment Month 12
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