Coinfection

Tenofovir-containing Regimen Works Better Over Time for HIV/HBV Coinfected People

HIV-positive people coinfected with hepatitis B virus (HBV) who were treated with 2 dually-active drugs -- one of them being tenofovir -- responded about as well as people taking only lamivudine or emtricitabine at 24 weeks, but over the longer term those on tenofovir plus either lamivudine or emtricitabine were more likely to maintain undetectable HBV viral load, according to a study published in a recent edition of AIDS.

HIV and HBV have overlapping transmission routes and many people are coinfected with both viruses. These viruses also share susceptibility to certain antiviral drugs including tenofovir (Viread, also in several HIV combination pills), lamivudine (Epivir or 3TC), and emtricitabine (Emtriva, or combined with tenofovir in Truvada).

Treatment guidelines recommend that HIV/HBV coinfected people should include at least one of these dually-active drugs in their antiretroviral therapy (ART) regimen. Tenofovir has a higher barrier to resistance than lamivudine or emtricitabine and is generally the preferred option if it is available and patients do not have pre-existing kidney problems. It is not yet clear whether combining 2 dually-active drugs offers an advantage.

Chloe Thio from Johns Hopkins University and colleagues looked at factors associated with short-term and long-term HBV suppression in a multinational cohort of HIV/HBV coinfected people receiving dually-active antiretroviral treatment.

The analysis included 115 coinfected patients participating in 2 global randomized clinical trials conducted by the AIDS Clinical Trials Group that compared different antiretroviral regimens. Participants could be either hepatitis B "e" antigen (HBeAg) positive or negative.

In these studies 56 participants received a regimen that contained only a single drug active against HBV -- either lamivudine or emtricitabine -- while 59 people took an ART regimen containing tenofovir plus lamivudine or emtricitabine.

The primary endpoint was HBV viral suppression (HBV DNA <200  IU/mL) after 24 weeks of treatment, but the researchers continued to follow participants for longitudinal outcomes through 144 weeks. People who experienced HBV viral rebound underwent viral genetic sequencing for drug resistance mutations.

Results

• Overall, 60% of participants had HBV viral load <200  IU/mL at 24 weeks, rising to 79% at 144 weeks.
• The likelihood of viral suppression at week 24 did not differ significantly between people treated with tenofovir plus lamivudine or emtricitabine and those taking lamivudine or emtricitabine as their only HBV-active drug.
• At 144 weeks, however, a significantly higher proportion of people taking tenofovir plus lamivudine or emtricitabine had HBV DNA <200 IU/mL, compared to those taking only lamivudine or emtricitabine.
• Pre-treatment factors associated with 24 week viral suppression included baseline HBV DNA level, CD4 T-cell count, and AST level.
• Looking at longer-term outcomes, lower pre-treatment HBV DNA was the only factor predicting HBV suppression at week 144.
• A higher proportion of HBeAg-negative patients achieved HBV suppression at any point, regardless of treatment group.
• All 12 patients who experienced emergence of drug-resistant HBV mutations were taking lamivudine or emtricitabine without tenofovir.

"[Tenofovir]-based dual HBV-active antiretroviral therapy is preferred to treat HIV/HBV coinfected patients," the study authors concluded.

However, their findings are also consistent with tenofovir being more potent than lamivudine or emtricitabine, and tenofovir alone -- which was not compared -- might have worked as well as the dually active combination.

"In resource-limited settings in which [tenofovir] may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication," the researchers added.

9/16/16

Reference

CL Thio, L Smeaton, K Hollabaugh, et al. Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks. AIDS 29(10):1173-1182. June 19, 2015.