Treating HIV/HBV Coinfection in Africa

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http://www.hivandhepatitis.com/hiv_hbv_co_inf/2011/07082011_a.html

HIVandHepatitis.com

Treating HIV/HBV Coinfection in Africa

SUMMARY

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.

By Liz Highleyman

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.

Gail s 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.

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.

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

106 out of 1771 HIV positive study participants, or 6%, were HIV/HBV

coinfected.

Coinfected participants were more likely to be men, and had higher baseline

ALT, lower albumin, and lower platelet levels than HIV monoinfected people.

Median CD4 T-cell gains and HIV RNA suppression were similar across all

treatment groups.

9.4% of coinfected patients experienced hepatic flares, compared with just

0.02% of those with HIV alone.

33% of coinfected patients taking lamivudine experienced HBV DNA suppression (<

55 IU/ml) at 48 weeks -- not significantly more than the 13% suppression rate

for people taking non-HBV-active drugs.

Mortality was significantly higher among HIV/HBV coinfected participants

compared with HIV monoinfected patients (17.0% vs 11.4%, respectively), but this

did not differ according to use of HBV-active or non-HBV-active ART.

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 s, 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)