Objectives: To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV–HBV co-infected patients receiving HBV-active antiretrovirals.
Methods: One hundred and fifteen HIV–HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound.
Results: The proportion with HBV DNA below 200 IU/ml was 60% (95% confidence interval 50–69%) at 24 weeks and 79% (95% confidence interval 69–88%) at 144 weeks. Pretreatment factors associated with the primary outcome were HBV DNA, CD4+ T-cell count, and aspartate aminotransferase, but only pretreatment HBV DNA remained associated with long-term suppression (P < 0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual-therapy group achieved HBV DNA below 200 IU/ml (P = 0.007). A higher proportion of hepatitis B e antigen-negative patients (n = 57) achieved HBV DNA below 200 IU/ml at any point, regardless of the therapy group. All 12 patients with emergence of lamivudine-resistant mutants were in the monotherapy group.
Conclusions: TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV–HBV co-infected patients. In resource-limited settings in which TDF may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication.
aJohns Hopkins University, Baltimore, Maryland
bHarvard School of Public Health, Boston, Massachusetts, USA
cYRG Centre for AIDS Research and Education, Voluntary Health Services Hospital Campus, Taramani, Chennai
dNational AIDS Research Institute-ICMR, Pune, India
eUniversity of Zimbabwe Clinical Research Centre, College of Health Sciences, Harare, Zimbabwe
fCollege of Medicine, Johns Hopkins Research Project, Department of Medicine, Blantyre, Malawi
gNelson R Mandela School of Medicine, University of KwaZulu-Natal, Glenwood, South Africa
hUniversity of Colorado School of Medicine, Aurora, Colorado
iBrigham and Women's Hospital, Boston, Massachusetts
jUCLA David Geffen School of Medicine, Los Angeles, California, USA.
Correspondence to Chloe L. Thio, MD, Professor of Medicine, Johns Hopkins University, 855 N Wolfe St, 5th floor, Baltimore, MD 21205, USA. Tel: +1 410 614 6088; e-mail: email@example.com
Received 19 December, 2014
Revised 18 March, 2015
Accepted 20 March, 2015