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Peginterferon (Pegasys) and Weight-Based Ribavirin for 72 Weeks in HIV+ Early Responders
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16th Conference on Retroviruses and Opportunistic Infections,
February 8-11, 2009, Montreal
Mark Mascolini
Complete early virologic response (EVR) predicted sustained virologic response (SVR) in a three-part AIDS Clinical Trials Group (ACTG) study called SLAM-C and numbered A5178 [1]. But partial EVR did not predict sustained response.
Raymond Chung and ACTG colleagues proposed that complete EVR "should be utilized in the guidance of HCV/HIV-co-infected [patients], particularly when extended treatment regimens are used."
In step 1 of SLAM-C, HIV/HCV-coinfected people took pegylated interferon (PEG) and weight-based ribavirin (1 g if 75 kg or under, 1.2 g if above 75 kg) for 12 weeks, then underwent biopsy. In step 2, people without EVR at week 12--defined as at least a 2-log (100-fold) drop in HCV RNA or an HCV load below 600 IU/mL--were randomized to PEG monotherapy maintenance or to observation for 72 weeks [2]. Chung presented results of step 3, which assigned patients with a week-12 EVR to PEG plus weight-based ribavirin for another 60 weeks plus 24 weeks of follow-up off treatment.
Steps 1 and 2 included adults with an HIV load below 50,000 copies and a CD4 count above 200 while taking a stable antiretroviral regimen or no antiretrovirals. Participants had to be HCV RNA positive with at least Metavir stage 1 disease on liver biopsy within 104 weeks. No one could have decompensated liver disease. Patients were eligible for step 3 if they had an EVR and tolerated PEG and weight-based ribavirin in step 1.
Step 3 included 169 people, 43% white, 37% black, and 15% Hispanic. Median age was 48 years, and 44% reported a history of injecting drugs. Median body mass index measured 25 kg/m(2). Most people (89%) were taking antiretrovirals, 86% had an HIV load below 50 copies, and median CD4 count stood at 316. Three quarters had genotypes 1 or 4, and 29% had interferon experience.
Of 146 step-3 patients with data at 96 weeks, 35 (24%) had a partial EVR (at least a 2-log drop in viral load) and 111 (76%) had a complete EVR (HCV RNA below 600 IU/mL). Seventy-five people (51%) with an EVR had an SVR, including 62% with a complete EVR and only 17% with a partial EVR, a highly significant difference (P < 0.0001). (from Jules: Chung also reported that 43% with prior treatment achieved SVR). Among complete responders, race had no impact on SVR. Among all people enrolled in step 1, 25% had an SVR.
In univariate analysis, HCV genotype 2 or 3 (versus 1 or 4) predicted SVR (82% versus 42%, P < 0.001), as did taking interferon for the first time in this trial (60% versus 30%, P = 0.001), a complete EVR (62% yes versus 17% no, P < 0.001), and black versus nonblack race/ethnicity (P = 0.05).
Fifty-one of 146 people (35%) discontinued step 3 prematurely, 14 because of fatigue, 6 because of cytopenia, and 4 because of depression. Three people died, 2 from myocardial infarction and 1 from a heroin overdose. Of those who dropped out before week 72, 55% did so between weeks 48 and 72. Ninety-five people completed all 72 weeks, and 60 of them (63%) had an SVR.
Chung proposed that the strong positive predictive value of complete EVR for SVR "implies that failure to clear virus by week 12 will identify most patients who will not achieve SVR." He also maintained that, despite the single-arm design of step 3, the results suggest that high SVRs may be possible with extended PEG plus weight-based ribavirin in people who can tolerate the regimen.
References
1. Chung R, Umbleja T, Butt A, et al. SLAM-C (ACTG A5178): role of early virologic response in extended therapy with PEG-interferon and weight-based ribavirin in HCV/HIV co-infected. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 103LB.
2. Sherman K, Andersen J, Butt A, et al. Sustained long-term antiviral maintenance with pegylated interferon in HCV/HIV-co-infected patients: early viral response and effect on fibrosis in treated and control subjects. 15th Conference on Retroviruses and Opportunistic Infections, February 3-6, 2008, Boston. Abstract 59.
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