Southern African study shows tenofovir associated with lower risk of HBV resistance than 3TC among HIV-HBV-co-infected people starting antiretroviral therapy

Research published in the Journal of Acquired Immune Deficiency Syndromes shows the clear superiority of tenofovir-containing antiretroviral regimes for people in sub-Saharan Africa co-infected with HIV and hepatitis B virus (HBV). Outcomes were compared one year after starting treatment according to the use of tenofovir with FTC (emtricitabine, Emtriva)/ 3TC (lamivudine, Epivir) or 3TC alone. The risk of HBV resistance was significantly lower for people taking a tenofovir-containing regimen.

“Tenofovir-containing first-line cART [combination antiretroviral therapy] provided potent HBV-active therapy with a superior resistance profile to lamivudine monotherapy,” comment the authors. “Our findings together with previous reports, provide support for use of tenofovir over lamivudine monotherapy in HIV-HBV co-infected persons in resource-limited settings.”

It is estimated that up to 15% of HIV-positive people in sub-Saharan Africa are co-infected with HBV. People starting antiretroviral therapy in this region are not routinely screened for hepatitis B surface antigen (HBsAg). As a result, co-infected people often receive an HIV treatment combination that has 3TC as the only drug with activity against HBV. This can lead to the rapid emergence of HBV drug resistance and poorer liver-related outcomes.

The anti-HIV drug tenofovir is also active against HBV and previous research has show that it works against 3TC-resistant virus. Moreover, tenofovir-containing HIV treatment combinations invariably include either FTC or 3TC, meaning that co-infected people receive two drugs with activity against HBV. The World Health Organization (WHO) recommends that HIV/HBV-co-infected people should be treated with a tenofovir-containing combination.

Despite this recommendation, an international team of investigators were concerned that no research had compared HBV-related outcomes in co-infected people according to the use of  3TC or tenofovir in first-line antiretroviral therapy.

They therefore designed a prospective study involving participants recruited at six sites in Zambia and South Africa, who started HIV therapy between 2007 and 2008.

A total of 1087 individuals were enrolled in  the study. Baseline screening showed that 92 individuals had HBsAg.

Of the 92 co-infected participants, 54 received 3TC and 38 tenofovir. HBV DNA results were available for 70 participants. These showed that median pre-treatment HBV DNA was 5.39 log₁₀ iu/ml. This did not differ between the 3TC- and tenofovir-treated participants.

There was a 13% prevalence of occult HBV infection (absence of HBsAg and a very low HBV viral load). The most common HBV genotype was A1. Two individuals had baseline resistance to the anti-HBV drug entecavir (Baraclude).

Overall, 81% of mono-infected and 72% of co-infected participants were still in care twelve months after starting therapy. Closer analysis of the co-infected participants showed that 74% of the 3TC-treated patients and 68% of those taking a tenofovir-containing regimen were retained in care and were still taking their first-line combination.

Twelve-month CD4 cell gains were comparable between the mono-infected participants (177 cells/mm³) and co-infected participants (159 cells/mm³). Among the co-infected people, CD4 cell count increased by 155 cells/mm³ for 3TC-treated patients and by 161 cells/mm³ for tenofovir-treated patients.

The rate of HBsAg loss did not differ according to the use of 3TC or tenofovir (20 vs 18%). The authors note these outcomes “compare favourably to the low background rate of spontaneous HBV clearance in untreated patients”.

Data on HBV-DNA suppression were available for 71% of participants.

HBV suppression was achieved by 62% of 3TC-treated individuals and by 71% of those taking tenofovir, a non-significant difference. The median fall in HBV viral load was also comparable between the two groups.

Of the 45 participants with occult HBV infection, 45 (82%) were retained in follow-up. It was possible to generate an HBV-DNA result for 39 (87%) of these individuals. These results showed that 91% of the 3TC-treated participants and all the tenofovir-treated individuals had an undetectable HBV viral load.

After twelve months of therapy, 16 co-infected participants had a detectable HBV viral load. Viral sequencing was successful on samples from twelve people (eight treated with 3TC; four with tenofovir). Resistance to 3TC was detected in half the patients treated with this agent. None of the people receiving tenofovir had resistance to this drug.

“Lamivudine is known to have a low genetic barrier to resistance,” note the authors. “Moreover, lamivudine resistance induces cross-resistance to emtricitabine, telbivudine and entecavir, thus reducing the options for subsequent treatment. By contrast, tenofovir has a good resistance profile.”

The authors conclude, “In countries with high HBV endemicity, all HIV-infected individuals should be screened for HBsAg before starting cART. Co-infected patients with an indication for treatment of either HBV and/or HIV should receive a triple combination of agent, including tenofovir.”