Coinfection

Tenofovir Is Highly Effective for HIV/HBV Coinfection, Meta-analysis Shows

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Tenofovir, which has potent activity against both HIV and hepatitis B virus (HBV), is the most effective hepatitis B treatment for HIV/HBV coinfected people, according to a 23-study meta-analysis described in the July 10, 2013, issue of the open-access journal PLoS One. Combining it with emtricitabine did not improve hepatitis B response.

Due to overlapping transmission routes, many people are coinfected with both HIV and HBV. A few antiretroviral drugs approved for HIV are also active against HBV, including lamivudine (3TC or Epivir), emtricitabine (FTC or Emtriva), and tenofovir disoproxil fumarate (Viread); emtricitabine and tenofovir are also ingredients in the HIV combination pills Truvada, Atripla, Complera, and Stribild. Lamivudine and emtricitabine 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 HIV/HBV coinfected people treated with tenofovir, stratified by prior or concurrent use of lamivudine and emtricitabine.

Tenofovir has been shown to be highly effective against hepatitis B and has a low barrier to resistance. However, several questions remain unanswered regarding tenofovir for HIV/HBV coinfected people, 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 efficacy due viral resistance.

The researchers analyzed data from 23 mostly observational studies that included a total of 550 HBV/HIV coinfected patients treated with tenofovir. Duration of follow-up lasted up to 7 years (tenofovir was FDA-approved for HIV in 2001), but the main analysis was limited to 3 years in order maintain a large enough number for sufficient statistical power.

Results

  • Overall, the proportion of patients achieving full suppression of HBV replication after 1 year of treatment was 57.4%.
  • Viral suppression rates increased to 79.0% at 2 years and 85.6% at 3 years, respectively.
  • 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 lamivudine or emtricitabine to tenofovir was not associated with significant improvement in treatment response.
  • Use of lamivudine or emtricitabine in the past did not significantly impair current response to tenofovir.

"[Tenofovir] suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected 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 59% treatment response rate for HIV/HBV coinfected patients in this analysis was lower than rates seen in studies of HIV negative patients with HBV alone: around 80%-90% at 1 year and 90%-100% at 2 years, with better response among hepatitis B "e" antigen (HBeAg) negative compared with HBeAg positive patients.

Although not apparent in this analysis, some prior studies have seen higher viral breakthrough rates for coinfected patients than for those with HBV alone. Among coinfected people taking lamivudine 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 characterized. Only 2 studies compared patients randomly assigned to different treatment arms.

Another limitation is that the analysis did not include adverse events. While tenofovir is generally safe and well-tolerated, it can cause bone loss and kidney impairment. "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.

8/28/13

Reference

H Price, D Dunn, D Pillay, et al. Suppression of HBV by Tenofovir in HBV/HIV Coinfected Patients: A Systematic Review and Meta-Analysis. PLoS One 8(7):e68152. July 10, 2013.