By
Liz Highleyman
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 log10 copies/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.