Antiretroviral Treatment Outcomes in HIV-HBV Co-infected Patients in Southern Africa

NCT02060162 | Completed

• 1 other identifier: F160229001
• Study Type: observational
• Target: 897
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective HIV cohort that aims to establish causes of liver disease among HIV-infected individuals in Zambia, including viral hepatitis and alcohol.

Conditions

Hepatitis B Virus; HIV; Antiretroviral Therapy; Africa; Liver Fibrosis; Alcohol Use Disorder

Keywords

antiretroviral therapy; Hepatitis C virus

Outcome Measures

Primary Outcomes (1)

• Immunological response

  A linear mixed effect model will be used to evaluate immunological response to ART in patients with and without viral hepatitis

  12 months post enrollment

Secondary Outcomes (8)

• HIV virological response

  12 months post enrollment

• Mortality

  12 months

• Hepatotoxicity events

  6 and 12 months

• Prevalence liver fibrosis

  Baseline and one year after start of ART

• HBV drug resistance

  1 and 2 years post enrollment

Study Arms (2)

HIV/HBV co-infected

150-200 patients in Zambia and 250-300 across all sites

Other: Standard of care

HIV mono-infected

700-750 patients in Zambia and 1600-1700 across all sites

Other: Standard of care

Interventions

Standard of care OTHER

routine standard of care per Ministry of Health protocol including blood draws and examinations.

HIV mono-infected; HIV/HBV co-infected

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Enrollment of 1,900 consecutive patients starting ART (900 in Zambia and 1,000 in Mozambique) is planned.

You may qualify if:

• HIV-infected
• Male or female aged ≥18 years
• ART naïve
• ART eligible as defined by Zambian or WHO treatment guidelines
• Initiating an ART regimen including at least 3 drugs at one of the study sites.
• Willing to provide signed informed consent and be followed at the clinical site.

You may not qualify if:

• Patients who are not planning to remain in the catchment area from which they were recruited for the duration of the study

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Centre for Infectious Disease Research in Zambia: collaborator
• University of Bern: collaborator

Study Sites (1)

Centre for Infectious Disease Research in Zambia

Lusaka, Zambia

Location

Related Publications (23)

• Barth RE, Huijgen Q, Taljaard J, Hoepelman AI. Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis. Int J Infect Dis. 2010 Dec;14(12):e1024-31. doi: 10.1016/j.ijid.2010.06.013. Epub 2010 Sep 25.

  PMID: 20870439 BACKGROUND

• Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D; BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1001-10. doi: 10.1056/NEJMoa051285.

  PMID: 16525137 BACKGROUND

• Davies J, van Oosterhout JJ, Nyirenda M, Bowden J, Moore E, Hart IJ, Zijlstra EE, Chaponda M, Faragher B, Beeching NJ, Beadsworth MB. Reliability of rapid testing for hepatitis B in a region of high HIV endemicity. Trans R Soc Trop Med Hyg. 2010 Feb;104(2):162-4. doi: 10.1016/j.trstmh.2009.10.010.

  PMID: 19931107 BACKGROUND

• De Luca A, Bugarini R, Lepri AC, Puoti M, Girardi E, Antinori A, Poggio A, Pagano G, Tositti G, Cadeo G, Macor A, Toti M, D'Arminio Monforte A; Italian Cohort Naive Antiretrovirals Study Group. Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naive HIV-infected subjects. Arch Intern Med. 2002 Oct 14;162(18):2125-32. doi: 10.1001/archinte.162.18.2125.

  PMID: 12374521 BACKGROUND

• Di Bisceglie AM, Maskew M, Schulze D, Reyneke A, McNamara L, Firnhaber C. HIV-HBV coinfection among South African patients receiving antiretroviral therapy. Antivir Ther. 2010;15(3 Pt B):499-503. doi: 10.3851/IMP1494.

  PMID: 20516571 BACKGROUND

• Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z, Crowther L, Condreay LD, Woessner M, Rubin M, Brown NA. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med. 1999 Oct 21;341(17):1256-63. doi: 10.1056/NEJM199910213411702.

  PMID: 10528035 BACKGROUND

• Firnhaber C, Reyneke A, Schulze D, Malope B, Maskew M, MacPhail P, Sanne I, Di Bisceglie A. The prevalence of hepatitis B co-infection in a South African urban government HIV clinic. S Afr Med J. 2008 Jul;98(7):541-4.

  PMID: 18785395 BACKGROUND

• Hoffmann CJ, Charalambous S, Martin DJ, Innes C, Churchyard GJ, Chaisson RE, Grant AD, Fielding KL, Thio CL. Hepatitis B virus infection and response to antiretroviral therapy (ART) in a South African ART program. Clin Infect Dis. 2008 Dec 1;47(11):1479-85. doi: 10.1086/593104.

  PMID: 18937580 BACKGROUND

• Hoffmann CJ, Charalambous S, Thio CL, Martin DJ, Pemba L, Fielding KL, Churchyard GJ, Chaisson RE, Grant AD. Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B. AIDS. 2007 Jun 19;21(10):1301-8. doi: 10.1097/QAD.0b013e32814e6b08.

  PMID: 17545706 BACKGROUND

• KASOLO, F. (2003) Hepatitis B virus infection in human immunodeficiency virus seropositive patients at the University Teaching Hospital, Lusaka, Zambia: Interrelationship. IN SAKALA, I. (Ed.) Abstract no. B12601. The XV International Aids Conference, International Aids Society.

  BACKGROUND

• Kwon H, Lok AS. Hepatitis B therapy. Nat Rev Gastroenterol Hepatol. 2011 May;8(5):275-84. doi: 10.1038/nrgastro.2011.33. Epub 2011 Mar 22.

  PMID: 21423260 BACKGROUND

• Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, Dienstag JL, Heathcote EJ, Little NR, Griffiths DA, Gardner SD, Castiglia M. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003 Dec;125(6):1714-22. doi: 10.1053/j.gastro.2003.09.033.

  PMID: 14724824 BACKGROUND

• Lok AS, Zoulim F, Locarnini S, Bartholomeusz A, Ghany MG, Pawlotsky JM, Liaw YF, Mizokami M, Kuiken C; Hepatitis B Virus Drug Resistance Working Group. Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology. 2007 Jul;46(1):254-65. doi: 10.1002/hep.21698.

  PMID: 17596850 BACKGROUND

• Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008 Dec 4;359(23):2442-55. doi: 10.1056/NEJMoa0802878.

  PMID: 19052126 BACKGROUND

• Nagu TJ, Bakari M, Matee M. Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania. BMC Public Health. 2008 Dec 19;8:416. doi: 10.1186/1471-2458-8-416.

  PMID: 19099553 BACKGROUND

• Nikolopoulos GK, Paraskevis D, Hatzitheodorou E, Moschidis Z, Sypsa V, Zavitsanos X, Kalapothaki V, Hatzakis A. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clin Infect Dis. 2009 Jun 15;48(12):1763-71. doi: 10.1086/599110.

  PMID: 19435436 BACKGROUND

• Nyirenda M, Beadsworth MB, Stephany P, Hart CA, Hart IJ, Munthali C, Beeching NJ, Zijlstra EE. Prevalence of infection with hepatitis B and C virus and coinfection with HIV in medical inpatients in Malawi. J Infect. 2008 Jul;57(1):72-7. doi: 10.1016/j.jinf.2008.05.004. Epub 2008 Jun 13.

  PMID: 18555534 BACKGROUND

• Oshitani H, Kasolo F, Tembo C, Mpabalwani M, Mizuta K, Luo N, Suzuki H, Numazaki Y. Hepatitis B virus infection among pregnant women in Zambia. East Afr Med J. 1995 Dec;72(12):813-5.

  PMID: 8689985 BACKGROUND

• Otegbayo JA, Taiwo BO, Akingbola TS, Odaibo GN, Adedapo KS, Penugonda S, Adewole IF, Olaleye DO, Murphy R, Kanki P. Prevalence of hepatitis B and C seropositivity in a Nigerian cohort of HIV-infected patients. Ann Hepatol. 2008 Apr-Jun;7(2):152-6.

  PMID: 18626434 BACKGROUND

• 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.

  PMID: 21555823 BACKGROUND

• Selabe SG, Lukhwareni A, Song E, Leeuw YG, Burnett RJ, Mphahlele MJ. Mutations associated with lamivudine-resistance in therapy-naive hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients. J Med Virol. 2007 Nov;79(11):1650-4. doi: 10.1002/jmv.20974.

  PMID: 17854040 BACKGROUND

• Wiersma ST, McMahon B, Pawlotsky JM, Thio CL, Thursz M, Lim SG, Ocama P, Esmat G, Mendy M, Bell D, Vitoria M, Eramova I, Lavanchy D, Dusheiko G; World Health Organization Department of Immunization, Vaccines and Biologicals. Treatment of chronic hepatitis B virus infection in resource-constrained settings: expert panel consensus. Liver Int. 2011 Jul;31(6):755-61. doi: 10.1111/j.1478-3231.2010.02373.x. Epub 2011 Feb 15.

  PMID: 21645206 BACKGROUND

• Vinikoor MJ, Sinkala E, Chilengi R, Mulenga LB, Chi BH, Zyambo Z, Hoffmann CJ, Saag MS, Davies MA, Egger M, Wandeler G; IeDEA- Southern Africa. Impact of Antiretroviral Therapy on Liver Fibrosis Among Human Immunodeficiency Virus-Infected Adults With and Without HBV Coinfection in Zambia. Clin Infect Dis. 2017 May 15;64(10):1343-1349. doi: 10.1093/cid/cix122.

  PMID: 28158504 DERIVED

Related Links

• University of North Carolina website

Biospecimen

Retention: SAMPLES WITH DNA

Specimen storage is optional and participants will provide additional informed consent. The laboratory will store leftover blood specimens for up to 5 years for hepatitis related serologic, immunological, and virologic studies pending availability of funding. Use of specimens for any tests outside the realm of the goals and objectives of this study will require additional approval by the Zambian IRB.

MeSH Terms

Conditions

Hepatitis B; Liver Cirrhosis; Alcoholism; Hepatitis C

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Flaviviridae Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Roma Chilengi, MD

  Centre for Infectious Disease Research in Zambia

  PRINCIPAL INVESTIGATOR

• Michael Vinikoor, MD

  Centre for Infectious Disease Research in Zambia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 9, 2014
• First Posted: February 11, 2014
• Study Start: October 1, 2013
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: November 12, 2021

Record last verified: 2021-11

Locations

ZA (1)