Numerous studies have shown that HIV-HCV coinfected individuals typically do not respond as well as HIV negative individuals to interferon-based therapy for hepatitis C. However, the relative efficacy of the 2 marketed types of pegylated interferon alfa -- 2a (Pegasys) and 2b (PegIntron) -- in coinfected people has not been extensively studied.

As reported at the XVII International AIDS Conference last week in Mexico City, Eugenia Vispo and colleagues performed an analysis to determine whether Pegasys and PegIntron -- which have different molecular weights and thus different pharmacokinetic properties -- might work differently in HIV-HCV coinfected patients. The investigators hypothesized that such differences might be more pronounced in HIV positive patients, in whom treatment response is impaired.

The researchers retrospectively analyzed 218 HCV-HIV coinfected patients recruited at one referral center in Spain to enroll in 2 Phase IV treatment trials, PRESCO and EXTENT. In both trials, participants received standard doses of either Pegasys (n = 138) or PegIntron (n = 80) plus 1000-1200 mg/day weight-based ribavirin. Baseline characteristics including sex, age, CD4 cell count, HIV RNA, HCV RNA, and liver fibrosis stage were comparable in both groups.

Results

• Through week 24, patients receiving Pegasys were more likely to achieve undetectable HCV RNA than those receiving PegIntron:

• Week 4: 45% vs 27%, respectively:

- Genotypes 2/3: 85% vs 50%;
- Genotypes 1/4: 23% vs 18%.

• Week 12: 65% vs 45%, respectively;

- Genotypes 2/3: 93% vs 81%;
- Genotypes 1/4: 50% vs 34%.

• Week 24: 75% vs 55%, respectively.

- Genotypes 2/3: 92% vs 87%;
- Genotypes 1/4: 66% vs 46%.

• Differences in response were more pronounced among people with genotypes 1 or 4, and diminished over time among people with genotypes 2 or 3.

• In a multivariate analysis, factors that independently predicted undetectable HCV RNA at week 24 were HCV genotype 2 or 3, lower baseline HCV RNA, not using zidovudine (AZT; Retrovir) (OR 0.30; P = 0.02), and treatment with Pegasys as opposed to PegIntron (OR 2.12; P = 0.04).

Based on these findings, the researchers concluded, "The intrinsic antiviral effect is higher for [pegylated interferon alfa-2a] than for [pegylated interferon alfa-2b] in the HIV setting."

They suggested that "An insufficient sustained antiviral effect at the end of weekly interval administration of [pegylated interferon alfa-2b] due to its shorter half-life could explain his observation."

The investigators did not look at sustained virological response (SVR), or continued undetectable HCV RNA 24 weeks after completion of therapy, which typically lasts 24 weeks for people with genotypes 2 or 3 and 48 weeks for people with genotypes 1 or 4 -- though many experts recommend 48 weeks for all coinfected people regardless of genotype. During the discussion after the presentation, Vispo indicated that further analysis of longer-term outcomes is ongoing, but that response at week 24 is known to be a good predictor of SVR.

Hospital Carlos III, Infectious Diseases and Pharmacokinetic & Pharmacogenetic Unit, Madrid, Spain.

8/15/08

Reference
E Vispo, P Barreiro, S Rodriguez-Novoa, and others. Distinct hepatitis C virus kinetics in HIV-infected patients treated with ribavirin plus either pegylated interferon alfa-2a or alfa-2b. XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Abstract THAB0206.