Coinfection

Treating HIV/HBV Coinfection in Africa

Antiretroviral therapy regimens containing lamivudine did not provide notable benefit or reduce mortality among HIV/HBV coinfected patients in South African, suggesting that tenofovir (Viread) may be a better option.




Hepatitis B virus (HBV) is endemic in many parts of the world and HIV/HBV coinfection is common. Some nucleoside/nucleotide analog drugs are active against both HBV and HIV and coinfected patients are advised to include these in their antiretroviral therapy (ART) regimen -- but some may be more beneficial than others.As described in the June 29, 2011, advance online edition of AIDS, PHIDISA II was a randomized study of antiretroviral treatment for HIV positive South African military personnel and their families.Gail Matthews and fellow investigators with the PHIDISA II study team looked at hepatitis B and HIV disease outcomes among HIV/HBV confected patients according to whether or not they used antiretroviral agents that were dually active against HBV.

Participants were assigned to receive 2 nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) pairs -- zidovudine (AZT; Retrovir) plus didanosine (ddI; Videx), or lamivudine (3TC; Epivir) plus stavudine (d4T; Zerit) -- in a 2 x 2 factorial design.

Of these agents, only lamivudine is active against HBV. These dual-NRTI backbones contain drugs that are no longer recommended in the U.S. and Europe due to toxicity, but they are still used in resource-limited countries because of their affordability. Among newer NRTIs widely used in wealthier countries, tenofovir (Viread, also in the Truvada and Atripla coformulations) is active against HBV, while abacavir (also in Trizivir and Epzicom) is not.

The investigators compared outcomes in people receiving HBV-active or non-HBV-active ART, looking at immunological recovery, HIV RNA suppression, HBV DNA suppression, hepatic flares (spikes in liver enzyme levels), and mortality.

Results

In summary, the study authors wrote, "the use of lamivudine-containing ART in HIV/HBV participants in PHIDISA II resulted in little additional benefit over that of ART itself and failed to impact on the greater mortality in this group."

This data, they added, "provides strong support for recent guidelines advocating the use of tenofovir in all HIV/HBV coinfected individuals initiating ART."

"Overall the efficacy of [lamivudine] on markers of HBV disease in this HIV/HBV coinfected population was poor," they elaborated in their discussion. "Failure to suppress HBV DNA adequately could not be explained by non-adherence, switches in medication or the occurrence of viral rebound in previously suppressed individuals, and can only be attributed to the inadequacy of [lamivudine] for HBV control in this population."

"The increased mortality in HIV/HBV coinfected individuals within this study highlights the ineffectiveness of this strategy and the urgent requirement for better management of HBV disease," they concluded.

Investigator affiliations: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; Project PHIDISA, South African Military Health Services, South African National Defence Force, Centurion, South Africa; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Bio-Analytical Research Corporation PTY LTD, Johannesburg, South Africa.

7/8/11

Reference
GV Matthews, P Manzini, Z Hu, et al (PHIDISA II study team). Impact of 3TC on HIV and HBV related outcomes in HIV/HBV individuals in a randomized clinical trial of antiretroviral therapy in South Africa. AIDS (abstract). June 29, 2011 (Epub ahead of print)