Patterns and causes of suboptimal response to tenofovir-based therapy in individuals coinfected with HIV and hepatitis B virus.

Abstract

BACKGROUND:

Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART).

METHODS:

One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA.

RESULTS:

Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified.

CONCLUSIONS:

Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.

• Authors: Gail V Matthews, Eric C Seaberg, Anchalee Avihingsanon, Scott Bowden, Gregory J Dore, Sharon R Lewin, Joe Sasadeusz, Peter A Revill, Margaret Littlejohn, Jennifer F Hoy, Robert Finlayson, Kiat Ruxrungtham, Melissa Saulynas, Stephen Locarnini, Chloe L Thio
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 56 Issue 9 Pg. e87-94 (May 2013) ISSN: 1537-6591 [Electronic] United States
• PMID: 23315316 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• DNA, Viral
• Organophosphonates
• Deoxycytidine
• Tenofovir
• Emtricitabine
• Adenine

Topics

• Adenine (administration & dosage, analogs & derivatives)
• Adult
• Aged
• Antiretroviral Therapy, Highly Active (methods)
• Antiviral Agents (administration & dosage)
• Australia
• Coinfection (drug therapy)
• DNA, Viral (blood)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Emtricitabine
• Female
• HIV Infections (complications, drug therapy)
• Hepatitis B virus (isolation & purification)
• Hepatitis B, Chronic (complications, drug therapy)
• Humans
• Male
• Medication Adherence
• Middle Aged
• Organophosphonates (administration & dosage)
• Tenofovir
• Thailand
• Treatment Failure
• United States