Combining tenofovir with FTC or 3TC boosts chances of HBV suppression for people co-infected with HIV

A study involving people co-infected with HIV and hepatitis B virus (HBV) shows that antiretroviral therapy that combines tenofovir with FTC or 3TC has the best chance of suppressing HBV replication to undetectable levels. The research is published in the online edition of Clinical Infectious Diseases. Factors associated with ongoing HBV replication included a low CD4 cell count and suboptimal adherence to HIV treatment.

“Combination therapy with TDF [tenofovir] and FTC/LMV [lamivudine or 3TC] increases the likelihood of sustained HBV DNA suppression,” comment the authors. “More advanced immunodeficiency and suboptimal compliance with the anti-HBV regimen decreased the likelihood of a sustained response in HIV-HBV co-infected subjects…emphasizing the importance of full adherence to maintain both HIV and HBV control is critical in HIV-HBV coinfected individuals.”

Tenofovir (Viread, also in the combination pills Truvada, Eviplera and Atripla) is a potent anti-HIV drug and is recommended for use in first-line antiretroviral therapy. The drug also has a powerful anti-HBV effect. Treatment guidelines therefore recommend that people co-infected with HIV and HBV should take an antiretroviral regimen that includes tenofovir.

Indeed, high rates of HBV suppression have been observed in co-infected people treated with tenofovir. However, a minority of individuals experience ongoing HBV replication. Investigators from Australia, Thailand and the United States wanted to identify why this was the case.

They therefore designed a prospective, observational research study involving HIV-infected people with chronic HBV infection, all of whom had experience of 3TC (lamivudine, which is also active against HBV) therapy. Most of the participants (73%) were gay men. At baseline, 49% were HBeAg-positive and hepatitis B DNA was detected in 29%. Overall, 90% were taking HIV therapy and 89% were treated with a regimen with anti-HBV activity.

The most common anti-HBV component of antiretroviral treatment was tenofovir in combination with either FTC or 3TC (57%). The remaining participants were taking a single drug that worked against HBV (19%, FTC or 3TC; 13% tenofovir), or no anti-HBV drug at all.

Participants were followed for a median of 2.8 years and a total of 1015 study visits were available for analysis. HBV DNA was detected at 21% of these visits.

After controlling for potential confounders, several factors were show to have an association with ongoing HBV replications. These included taking only one antiretroviral drug with activity against HBV (FTC/3TC monotherapy, p < 0.001; tenofovir monotherapy, p = 0.02).

Shorter duration of antiretroviral therapy was also associated with detection of HBV (under two years of cumulative treatment, p = 0.002). A CD4 cell count below 200 cells/mm³ was also significant. The investigators found this association “intriguing because it suggests that the degree of immunosuppression affects the ability to respond to anti-HBV therapy…these data support recommendations for the early initiation of HAART [highly active antiretroviral therapy] in HIV-HBV co-infected patients.”

A detectable HIV viral load (p < 0.001) and less than 95% adherence (p = 0.05) to antiretroviral treatment were also risk factors for the detection of HBV.

The investigators then explored the factors associated with HBV replication among people treated with tenofovir.

HBeAg positivity, a low CD4 cell count and a detectable HIV viral load were all identified as significant.

However, taking tenofovir in combination with FTC/3TC reduced the risk of HBV replication (p = 0.02).

The authors were also able to pinpoint three patterns of non-response in participants treated with tenofovir. These were the failure of therapy to ever achieve suppression of HBV replication; a rebound in HBV viral load; and transient 'blips' in HBV followed by a return to virologic suppression.  

“Therapy with TDF plus FTC or LMV is indeed superior to TDF monotherapy,” the authors conclude. “This finding was demonstrated in the entire cohort and also when the analysis was restricted to those taking TDF-based HAART regimen.”