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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02060162
First Posted: February 11, 2014
Last Update Posted: May 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Centre for Infectious Disease Research in Zambia
University of Bern
Information provided by (Responsible Party):
Michael Vinikoor, University of Alabama at Birmingham
  Purpose
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.

Condition Intervention
Hepatitis B Virus HIV Antiretroviral Therapy Africa Liver Fibrosis Alcohol Use Disorder Other: Standard of care

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Antiretroviral Treatment Outcomes in HIV-HBV Co-infected Patients in Southern Africa: a Collaborative Multi-country Prospective Cohort Analysis for International Epidemiologic Databases to Evaluate AIDS- Southern Africa (HIV/HBV-coinfection in IeDEA-SA)

Resource links provided by NLM:


Further study details as provided by Michael Vinikoor, University of Alabama at Birmingham:

Primary Outcome Measures:
  • Immunological response [ Time Frame: 12 months post enrollment ]
    A linear mixed effect model will be used to evaluate immunological response to ART in patients with and without viral hepatitis


Secondary Outcome Measures:
  • HIV virological response [ Time Frame: 12 months post enrollment ]
    Virological response will be evaluated using Cox regression analyses.

  • Mortality [ Time Frame: 12 months ]
    Deaths will be ascertained

  • Hepatotoxicity events [ Time Frame: 6 and 12 months ]
    These events will be defined as an increase in the level of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 time the upper limit within the first year of ART.

  • Prevalence liver fibrosis [ Time Frame: Baseline and one year after start of ART ]
    The prevalence of liver fibrosis will be measured to compare HIV/hepatitis coinfected versus HIV monoinfected patients using transient elastography.

  • HBV drug resistance [ Time Frame: 1 and 2 years post enrollment ]
    The presence of HBV drug resistance in co-infected patients who fail treatment after 1 year will be measured

  • Incidence of HBV infection [ Time Frame: 12 and 24 months post enrollment ]
    The incidence of HBV infection during ART will be measured.

  • Prevalence of HIV/HCV coinfection [ Time Frame: Baseline ]
    Describe prevalence of coinfection at ART initiation

  • Alcohol use patterns [ Time Frame: Baseline, 12, and 24 months ]
    Describe the proportion with unhealthy levels of drinking before and after ART


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.

Estimated Enrollment: 900
Study Start Date: October 2013
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
HIV/HBV co-infected
150-200 patients in Zambia and 250-300 across all sites
Other: Standard of care
routine standard of care per Ministry of Health protocol including blood draws and examinations.
HIV mono-infected
700-750 patients in Zambia and 1600-1700 across all sites
Other: Standard of care
routine standard of care per Ministry of Health protocol including blood draws and examinations.

Detailed Description:
The study will take place during routinely scheduled ART visits as per Ministry of Health guidelines. Routinely collected programmatic data will be used to assess general HIV outcomes (CD4 response, loss to follow-up, death) as well as collecting study specific data (hepatitis testing, questionnaire regarding risk factors for hepatitis/liver disease, and non-invasive liver scan) to address other aims. The study will be implemented at two sites in Southern Africa (Zambia and Mozambique) with a total enrollment across all sites of 1,900 participants. The Zambia site will only enroll 900.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Patients who are not planning to remain in the catchment area from which they were recruited for the duration of the study
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02060162


Locations
Zambia
Centre for Infectious Disease Research in Zambia
Lusaka, Zambia
Sponsors and Collaborators
University of Alabama at Birmingham
Centre for Infectious Disease Research in Zambia
University of Bern
Investigators
Principal Investigator: Roma Chilengi, MD Centre for Infectious Disease Research in Zambia
Principal Investigator: Michael Vinikoor, MD Centre for Infectious Disease Research in Zambia
  More Information

Additional Information:
Publications:
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. Review.
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.
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.
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.
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. Review.
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.
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.
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.
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.
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.
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. Review.
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.
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. Review.
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.
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.
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.
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.
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.
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.
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.
Selabe SG, Lukhwareni A, Song E, Leeuw YG, Burnett RJ, Mphahlele MJ. Mutations associated with lamivudine-resistance in therapy-naïve 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.
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. Review. Erratum in: Liver Int. 2012 Jan;32(1):174. Maimuna, Mendy [corrected to Mendy, Maimuna].

Responsible Party: Michael Vinikoor, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02060162     History of Changes
Other Study ID Numbers: F160229001
First Submitted: February 9, 2014
First Posted: February 11, 2014
Last Update Posted: May 24, 2017
Last Verified: May 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Vinikoor, University of Alabama at Birmingham:
antiretroviral therapy
Hepatitis C virus

Additional relevant MeSH terms:
Hepatitis
Hepatitis B
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human


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