Tenofovir, which has potent activity against both HIV and hepatitis B virus (HBV), is the most effective hepatitis B treatment for people with HIV and HBV co-infection, according to a 23-study meta-analysis described in the July 10, 2013 issue of the open-access journal PLoS One. Combining tenofovir with FTC did not improve hepatitis B response.
Due to overlapping transmission routes, many people are co-infected with both HIV and HBV. A few antiretroviral drugs approved for HIV are also active against HBV, including 3TC (lamivudine, Epivir), FTC (emtricitabine, Emtriva), and tenofovir (Viread). 3TC and FTC have similar structure and antiviral activity, though the former appears more prone to resistance; virus that develops resistance to one of these drugs will typically be cross-resistant to the other.
Huw Price from University College London and colleagues performed a systematic review and meta-analysis looking at outcomes among people with HIV and HBV co-infection treated with tenofovir, stratified by prior or concurrent use of 3TC and FTC.
Tenofovir has been shown to be highly effective against hepatitis B and has a low barrier to resistance. However, several questions remain unanswered about tenofovir for people with HIV and HBV co-infection, the study authors noted as background, including the proportion who achieve HBV viral load suppression and how long it takes; whether suppression is durable; and whether prior treatment with other HBV-active drugs compromises tenofovir effectiveness due to viral resistance.
The researchers analysed data from 23, mostly observational, studies that included a total of 550 people with HBV and HIV co-infection who had taken tenofovir. Duration of follow-up lasted up to seven years, but the main analysis was limited to three years in order maintain a large enough number for sufficient statistical power.
Overall, the proportion of study participants achieving full suppression of HBV replication after one year of treatment was 57%. Viral suppression rates increased to 79% at two years and 86% at three years. Among participants followed for longer periods, the proportion with undetectable HBV increased to 100%, though patient numbers were small. Virological rebound during tenofovir treatment was rare (2.4%).
Adding 3TC or FTC to tenofovir was not associated with significant improvement in treatment response. Use of 3TC or FTC in the past did not significantly impair current response to tenofovir.
"[Tenofovir] suppresses HBV to undetectable levels in the majority of HBV/HIV co-infected patients with the proportion fully suppressed continuing to increase during continuous treatment", the study authors concluded. "Prior treatment with [lamivudine or emtricitabine] does not compromise efficacy of [tenofovir] treatment. The use of combination treatment with [lamivudine or emtricitabine] offers no significant benefit over [tenofovir] alone."
In their discussion, they explained that the treatment response rate for people with HIV and HBV co-infection in this analysis was lower than rates seen in studies of HIV-negative people with HBV alone: around 80 to 90% at one year and 90 to 100% at two years, with better response among people who were hepatitis B 'e' antigen (HBeAg) negative compared with people who were HBeAg positive.
Although not apparent in this analysis, some prior studies have seen higher viral breakthrough rates for people with co-infection than for those with HBV alone. Among people with co-infection taking 3TC as their only HBV-active drug, about 90% develop resistance, while HBV resistance to tenofovir is rare.
As a limitation of their analysis, the authors noted that most of the included studies were observational, and participants who dropped out were not well characterised. Only two studies compared people randomly assigned to different treatment arms.
Another limitation is that the analysis did not include adverse events (side-effects). While tenofovir is generally safe and well-tolerated, it can cause bone loss and kidney impairment in susceptible individuals. "Future studies with longer follow-up duration will be required to determine the risk of treatment-associated adverse effects, such as renal and bone toxicity, in patients exposed to [tenofovir] for many decades", they wrote.