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  5th IAS Conference on HIV Pathogenesis, Treatment and Prevention
July 19th-22nd 2009
Capetown, South Africa
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HIV Regimens Lacking Nucleosides Tied to Higher SVR Rate With HCV Therapy
  5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
HIV-infected people taking antiretroviral regimens lacking nucleosides (NRTIs) had a higher sustained virologic response (SVR) rate than people taking nucleosides after 48 weeks of pegylated interferon/ribavirin for HCV infection in a small, partially randomized trial [1]. The trial found equivalent SVRs in people with and without HIV.
German researchers evaluated interferon/ribavirin in three groups: 60 HCV-infected people without HIV, 46 HIV/HCV-infected people taking no antiretrovirals, and 68 HIV/HCV-infected people taking antiretrovirals. The investigators randomized 48 people in this last group to an NRTI-containing regimen and 20 to an NRTI-free combination (two protease inhibitors or a protease inhibitor plus a nonnucleoside).
The HIV group not taking antiretrovirals was younger and had higher CD4 counts than the HIV-infected people taking antiretrovirals (median 39 years in the no-antiretroviral group versus 41 in the NRTI-containing group and 43 in the NRTI-free group; median 580 CD4s in the no-antiretroviral group versus 490 in the NRTI group and 390 in the no-NRTI group). Besides having a lower CD4 count than the NRTI-containing group, the NRTI-free group had a higher pretreatment HCV load (5.8 versus 5.4 log). Eleven people (55%) in the NRTI-free group and 30 (63%) in the NRTI-containing group had hard-to-treat HCV genotype 1 or 4.
HCV therapy consisted of 180 micrograms of pegylated interferon alfa-2a and 800 mg of ribavirin for 24 weeks in people with HCV genotype 2 or 3 and for 48 weeks in people with genotype 1 or 4. The protocol was amended to extend treatment to 48 weeks for everyone and to use a weight-based dose of ribavirin.
SVR rates were equivalent across the three main study groups, but in the antiretroviral-treated group, a significantly higher proportion of people taking no NRTIs than taking NRTIs had an SVR:
· HIV-negative SVR 54%
· All HIV-positive SVR 54%
· HIV-positive, no antiretroviral therapy SVR 59%
· HIV-positive, on antiretroviral therapy SVR 52%
· HIV-positive, NRTI-containing therapy SVR 42%
· HIV-positive, NRTI-free regimen SVR 75%
The SVR difference between people taking or not taking NRTIs was statistically significant (P = 0.012), while the difference between the groups on versus off antiretroviral therapy was not significant. The NRTI-containing and NRTI-free groups did not differ in proportions with genotypes 1 or 4 versus 2 or 3, use of weight-adjusted ribavirin, treatment duration, number of adverse events, or rate of treatment discontinuations for adverse events. The investigators did not attempt a statistical analysis to determine which factors favored an SVR without rather than with NRTIs. Nor did they explain the 2.4-to-1 randomization favoring NRTI-containing antiretroviral therapy or discuss statistical power calculations.
In the NRTI-containing group, two factors made an SVR less likely. A higher proportion without an SVR had genotype 1 or 4 (79% versus 40% with an SVR, P = 0.003), and pretreatment HCV load was higher in people who did not attain an SVR (5.7 versus 5.1 log with an SVR, P < 0.001). Factors that did not predict SVR in this analysis were gender, age, HIV transmission risk group, CD4 count, and type of NRTI-containing therapy.
1. Vogel M, Ahlenstiel G, Klausen G, et al. The effect of nucleoside free HAART on the treatment of chronic HCV infection. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract WEPEB235.