Coinfection

Coinfected People May Control HIV but not HBV on a Tenofovir Regimen

More then one-third of people coinfected with HIV and hepatitis B virus (HBV) did not achieve or maintain HBV suppression after 1 year of taking tenofovir (Viread), even though they had undetectable HIV viral load indicating good adherence, according to study findings presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston.

Tenofovir (also in the Truvada and Atripla combination pills) -- as well as lamivudine (Epivir) and emtricitabine (Emtriva) -- is active against both HIV and HBV. Treatment guidelines recommend that coinfected patients should include such dually active agents in their antiretroviral therapy (ART) regimen.

Kate Childs and colleagues from Kings College Hospital in London looked at HBV/HIV coinfected people with undetectable HIV but persistently detectable HBV after 48 weeks on tenofovir-containing ART.

The investigators searched a prospective clinical database, identifying 113 HIV/HBV coinfected patients. Of these 14 (or 12.4%) had detectable HBV DNA but undetectable HIV RNA after 48 weeks on tenofovir ART. Most (12 of 14) were men, the median age was 44 years, and 57% were hepatitis B "e" antigen (HBeAg) negative. Half had HBV genotype A, 29% had genotype E, 14% had genotype G, and 1 person had genotype D.

HBV can develop resistance to antiviral agents, especially when these drugs are used alone. Nearly two-thirds of participants had previously used lamivudine monotherapy (for a median of about 20 months prior to switching to a tenofovir-containing regimen), and one-third had previously taken tenofovir as the only HBV-active drug.

Results

• At baseline the median HBV DNA viral load was 7.74 log IU/mL.
• At baseline 36% of participants had HIV with evidence of lamivudine resistance, carrying the M204V mutation alone or with L180M and/or V173L.
• 9 of 14 participants (64%) had no known resistance mutations, and none showed evidence of tenofovir resistance.
• After 48 weeks of tenofovir-containing ART, median HBV DNA had fallen to 1.95 log IU/mL;
• 8 of the 14 patients (57%) had undetectable HBV DNA (< 2 log IU/mL) at week 48.
• HBV DNA became undetectable in 9 patients (64%) after a median 175 weeks of therapy.
• However, just over one-third (5 of 14 patients, or 36%) still had detectable HBV DNA a median of 199 weeks after starting tenofovir.
• Resistance testing after 48 weeks on tenofovir was done for 6 patients with detectable HBV DNA (the other 8 had viral loads too low to test):
• 2 showed persistent lamivudine mutations;
• 1 had wild-type HBV despite previous lamivudine resistance;
• 3 showed no known mutations.
• None of the participants developed the A194T mutation conferring resistance to tenofovir.

"Despite optimal adherence to tenofovir treatment, as evidenced by control of HIV, 14 patients failed to achieve an undetectable HBV DNA after 48 weeks of treatment," the researchers concluded.

"The long-term clinical significance of low level HBV viremia in this population is unclear," they added. "This may be an HIV specific issue or reflect cumulative HBV resistance allowing replication fitness."

Dept. of Genitourinary Medicine, Kings College Hospital; Institute of Liver Studies, Kings College Hospital, London, UK.

12/10/10

Reference
K Childs, D Joshi, I Carey, and others. Failure to control HBV replication despite control of HIV replication in co-infected patients on tenofovir-containing ART regimen -- cause for concern in HBV monoinfection? 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 737.