By Liz Highleyman

Hepatitis B virus (HBV) coinfection is common among HIV positive people in areas where hepatitis B is endemic, but how best to manage coinfected patients -- especially in resource-limited settings -- has not been extensively studied.

Prince Manzini from the South African Military Health Service and colleagues with the Phidisa II Study Group looked at the impact of treatment with lamivudine-containing combination antiretroviral therapy (ART) in HIV-HBV coinfected individuals.

Phidisa II was a randomized clinical trial comparing 4 combination ART regimens, 2 containing lamivudine and 2 without. The study included 1771 South Africans with symptomatic HIV disease or a CD4 count below 200 cells/mL. Patients with a positive hepatitis B surface antigen (HBsAg) test prior to randomization were identified as coinfected.

A total of 106 patients (6%) were HIV-HBV coinfected. This group was significantly more likely to be male, had lower platelet counts and serum albumin, and had higher ALT levels than HIV monoinfected patients. Baseline characteristics were well balanced, however, between the 57 participants receiving lamivudine-containing regimens and the 49 patients on non-lamivudine ART.

Over a median follow-up period of about 2 years, the researchers compared CD4 cell recovery and HIV RNA suppression between patients receiving lamivudine-containing and non-lamivudine regimens.

Episodes of hepatic flare -- liver inflammation indicated by serious ALT elevation -- were also assessed. Flares were defined as ALT > 135 IU/mL in patients with a normal baseline level or an increase of more than 1000 IU/mL in patients who started with an elevated level. They also used a more stringent definition, ALT > 225 IU/mL in patients with a normal baseline level or an increase of more than 3.5 x baseline level if initially high (equivalent to grade 3 hepatotoxicity.)

Results

	" Median change from baseline CD4 counts in HIV-HBV coinfected patients receiving lamivudine-containing and non-lamivudine regimens were as follows:
	6 months: 105 vs 84 cells/mm3; 12 months: 136 vs 127 cells/mm3; 24 months: 126 vs 192 cells/mm3; 36 months: 271 vs 217 cells/mm3.
	None of these differences were statistically significant (P > 0.05).
	There also were no significant differences between the treatment groups with regard to HIV RNA levels or median changes in ALT.
	Although median ALT levels remained stable over time in HIV monoinfected individuals, HIV-HBV coinfected patients experienced an overall decrease in median ALT levels.
	By month 24, ALT decreased by 7.5 IU/mL among patients taking lamivudine-containing ART, compared with 0.5 IU/mL for those using regimens without lamivudine.
	Serious hepatic flares were more than twice as common in the non-lamivudine ART group compared with the lamivudine-containing ART group (25% vs 11%).

"HIV-HBV coinfected individuals were more likely to have higher ALT and lower albumin and platelet counts at baseline, possible indicators of more severe underlying liver disease," the investigators concluded. "However, as described previously by the others, there was no suggestion that the presence of HIV-HBV coinfection impaired either the immunological or virological response to combination ART, irrespective of the use or not of [lamivudine].

"Reductions in overall serum transaminase levels relative to baseline were observed in HIV-HBV coinfected subjects receiving both [lamivudine-containing ART] and [non-lamivudine ART]," they continued. "Hepatic flare was substantially more common in coinfected patients compared t those with HIV monoinfection."

"The pathogenesis of hepatic flare in patients with HIV-HBV coinfection is often multifactorial and additional work to examine measures of HBV replication and serological changes during follow-up in this trial is ongoing and should provide valuable additional information," they added.

South African Military Health Service, Pretoria, South Africa.

7/31/09

Reference
P Manzini and others (Phidisa II Study Group). Impact of lamivudine (3TC)-containing combination antiretroviral therapy (cART) in South African patients co-infected with HIV and hepatitis B virus (HBV); a randomised, controlled trial (Phidisa II). 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract WePeB231.

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