Coinfection

ICAAC 2009: Resistance to Hepatitis B Drugs is Common among HIV-HBV Coinfected Patients Receiving Lamivudine-containing ART without Tenofovir (Viread)

Resistance to the hepatitis B drugs adefovir (Hepsera), entecavir (Baraclude), and telbivudine (Tyzeka) is common among HIV-HBV coinfected individuals treated with antiretroviral therapy (ART) regimens that include lamivudine (3TC; Epivir) without tenofovir (Viread, also in the Truvada and Atripla coformulations), according to a poster presented at 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009) this week in San Francisco. These findings support the recommendation that coinfected patients should be treated with ART regimens containing at least 2 drugs with dual activity against HIV and HBV.

Pawinee Wongprasit and colleagues from Thailand conducted a cross-sectional study of HIV-HBV coinfected patients who received lamivudine-containing ART.

Due to overlapping risk factors, infection with both HIV and HBV is common in Asia, where HBV is endemic. The prevalence of HBV infection among HIV positive individuals in that region is estimated to be 8%-10%, the investigators noted as background.

Lamivudine is a common component of ART and is often used as standard therapy for hepatitis B, but drug resistance is a barrier to long-term therapy. This is especially true for HBV, since lamivudine is frequently used as monotherapy (unlike ART for HIV). Although HBV DNA levels decrease by an average of 2.7 log₁₀copies/mL in HIV-HBV coinfected patients taking lamivudine for 1 year, the incidence of lamivudine-resistant HBV is about 20% per year in this population, according to the researchers.

The present study included 84 HIV-HBV coinfected patients treated at a medical school hospital between December 2007 and December 2008. About 75% were men and the mean age was 42 years. The median duration of ART use was 46 months and lamivudine use was 40 months. Participants had complete HIV viral load suppression (< 50 copes/mL) on a lamivudine-containing ART regimen and the median CD4 count was 352 cells/mm³.

Participants were categorized into 2 groups based on the presence of lamivudine resistance, defined as having HBV with the mutations M204V/I/S (YMDD), L180M/A181T, L80V/I, V173L, M204I, L180M/M204V, I169T/V173L/M250V, or T184G/S202I. Mutations associated with resistance to adefovir, entecavir, telbivudine, and tenofovir were also determined.

Results

• Of the 84 patients, 19 (23%) had HBV drug resistance.
• In a univariate analysis, there were no significant differences with regard to sex, age, ART regimen, liver function test results, or hepatitis B core or hepatitis C antibody positivity between the groups with and without lamivudine resistance.
• Patients with HBV drug resistance were more likely than those without to be hepatitis B "e" antigen (HBeAg) positive (68.4% vs 3.8%; P < 0.001).
• In a multivariate analysis, being HBeAg positive (odds ratio [OR] 16.64; P < 0.001) and duration of lamivudine use (OR 1.045; P = 0.046) were the only significant risk factors for HBV drug resistance.
• Of 19 patients with HBV drug resistance, all had lamivudine resistance, with the mutations M204V/I (95%), L180M/A181T (95%), L80V/I (47%), V173L (32%), and N236T (21%).
• Among these patients, 37% also had resistance to entecavir, 32% had resistance to telbivudine, and 26% had resistance to adefovir.

Based on these findings, the investigators concluded, "[lamivudine] resistance in HBV-HIV coinfected patients receiving [lamivudine]-containing HAART is common."

"Positive HBeAg and longer duration of [lamivudine] use are risk factors for [lamivudine] resistance," they continued. "In addition to [lamivudine] resistance, cross-resistance to other anti-HBV drugs is also frequently observed."

In resource-limited countries, HBeAg testing may be used to predict the likelihood of lamivudine resistance in coinfected patients, they suggested. They also suggested avoiding use of lamivudine as the sole agent active against HBV in a HAART regimen. "Combination of [tenofovir] plus [lamivudine] or [emtricitabine] is recommended in HBV-HIV coinfected patients in order to prevent the emergence of resistant HBV variants," they stated.

This recommendation is in accordance with current U.S. Department of Health and Human Services (DHHS) treatment guidelines for HIV-HBV coinfected individuals.

Faculty of Med. Ramathibodi Hosp., Mahidol Univ., Bangkok, Thailand; Bamrasnaradura Infectious Diseases Inst., Ministry of Publ. Hlth., Nonthaburi, Thailand.

9/15/09

Reference

P Wongprasit, W Manosuthi, and S Sungkanuparph. Hepatitis B Virus Drug Resistance in HIV-1 Infected Patients Receiving Lamivudine-Containing Antiretroviral Therapy. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. Abstract H-227.