HIVHBV Coinfection in Southern Africa and the Effect of Lamivudine- Versus Tenofovir-Containing cART on HBV Outcomes

Hamers, Raph L. MD, PhD*,†,‡; Zaaijer, Hans L. MD, PhD§,‖; Wallis, Carole L. PhD¶,#; Siwale, Margaret MD**; Ive, Prudence MD††; Botes, Mariette E. MD‡‡; Sigaloff, Kim C. E. MD, PhD*,†,‡; Hoepelman, Andy I. M. MD, PhD§§; Stevens, Wendy S. MD, MMed; Rinke de Wit, Tobias F. PhD*,†,‡; PharmAccess African Studies to Evaluate Resistance (PASER)

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 October 2013 - Volume 64 - Issue 2 - p 174–182
doi: 10.1097/QAI.0b013e3182a60f7d
Clinical Science

Background: This study assessed HIV–hepatitis B virus (HBV) coinfection in southern Africa in terms of prevalence, viral characteristics, occult HBV, and the effect of lamivudine- versus tenofovir-containing first-line combination antiretroviral treatment (cART) on HBV-related outcomes.

Methods: A multicenter prospective cohort of HIV-infected adults in Zambia and South Africa who initiated cART. Outcomes by month 12 on cART were immunological recovery, hepatitis B surface antigen (HBsAg) loss, viral suppression, and drug resistance. We used descriptive statistics, logistic regression, and linear mixed models.

Results: Of the 1087 participants, 92 were HBsAg seropositive, yielding a sample-weighted prevalence of 7.4% (95% confidence interval: 5.6 to 9.2), with 76% genotype HBV-A1. The estimated CD4 recovery on cART was similar between HIV monoinfection and HIV–HBV coinfection groups and between lamivudine- and tenofovir-treated participants. HBsAg loss was documented in 20% (4/20) of lamivudine-treated and 18% (3/17) of tenofovir-treated participants (P = 0.305). Viral suppression (HBV-DNA < 20 IU/mL) was achieved in 61.5% (16/26) of lamivudine-treated and 71.4% (15/21) of tenofovir-treated participants (P = 0.477). HBV pol sequencing demonstrated M204I (n = 3) and N236T (n = 1) resistance-associated mutations in 4 of 8 (50%) lamivudine-treated participants and none in tenofovir-treated participants. Occult HBV infection was present in 13.3% before cART, but by month 12, HBV-DNA was below the limit of detection (<15 IU/mL) in 90.5% (19/21) of lamivudine-treated and 100% (18/18) of tenofovir-treated participants (P = 0.179).

Conclusions: Tenofovir-containing first-line cART is preferred for HIV–HBV coinfection in Africa because of a superior resistance profile relative to lamivudine monotherapy. Extended follow-up will be needed to determine long-term complications of occult HBV coinfection. Improved access to HBsAg screening and tenofovir is needed.

*Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;

PharmAccess Foundation, Amsterdam, The Netherlands;

Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands;

§Department of Blood-Borne Infections, Sanquin, Amsterdam, The Netherlands;

Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;

Department of Molecular Medicine and Hematology, University of the Witwatersrand, Johannesburg, South Africa;

#Lancet Laboratories, Johannesburg, South Africa;

**Lusaka Trust Hospital, Lusaka, Zambia;

††Clinical HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa;

‡‡Muelmed Hospital, Pretoria, South Africa; and

§§Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.

Correspondence to: Raph L. Hamers, MD, PhD, Department of Global Health, Academic Medical Center of the University of Amsterdam, PharmAccess Foundation, Amsterdam Institute for Global Health and Development, Trinity Building C, Pietersbergweg 17, 1105 BM Amsterdam, The Netherlands (e-mail: r.hamers@aighd.org).

Supported by the Ministry of Foreign Affairs of The Netherlands (Grant 12454) and Stichting Aids Fonds.

The authors have no conflicts of interest to disclose.

Part of the data were presented at 19th Conference on Retroviruses and Opportunistic Infections, March 5–8, 2012, Seattle, WA (Abstract 794).

T.F.R.W. was the principal investigator. R.L.H., H.L.Z., C.L.W., I.M.H., W.S., and T.F.R.W. designed the study and developed the protocol. R.L.H. and K.C.E.S. contributed to implementation. M.S., P.I., and M.B. established the cohort and supervised data collection. H.L.Z., C.L.W., and W.S. supervised the laboratory testing. R.L.H. conceived and conducted the data analyses. R.L.H. drafted the manuscript, with assistance from H.L.Z. H.L.Z., C.L.W., K.C.E.S., I.M.H., and T.F.R.W. provided valuable input to interpretation of the data and critically reviewed the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript.

The funders had no role in the study design, data collection, data analysis, data interpretation, decision to publish, or writing of the report. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above.

Received May 03, 2013

Accepted July 16, 2013

© 2013 by Lippincott Williams & Wilkins