Background:  HCV levels are 10x higher in HIV(+) compared with HIV(-) hosts.  This has been attributed to diminished control of HCV replication with HIV infection. The impact of HAART on HCV RNA and reactivation of HCV is unknown in U.S. cohorts.  We analyzed the dynamics of HCV RNA and the frequency of grade 3+ ALT in coinfected subjects enrolling in ACTG trials. We also sought to determine whether HCV impairs successful immune reconstitution. 

Methods:  We prospectively analyzed 29 co-infected patients who completed at least 16 weeks of HAART in 4 trials, and retrospectively analyzed 31 patients with available plasma from 2 other completed HAART trials (ACTG 320, 343). HCV RNA was measured by quantitative PCR from plasma at baseline and on treatment to week 48. A retrospective case-control analysis of 40 HCV RNA (+) patients compared with 133 HCV RNA (-) patients from ACTG 343 was also performed.

Results:  60 patients completed at least 16 weeks of HAART in both groups.  Baseline mean log₁₀ HIVRNA 4.45, CD4 311, and log₁₀ HCVRNA 6.05.  Nearly all patients (88%) reduced HIV RNA to <500 by week 16; mean increase of CD4 by week 48 was +132.  Overall, mean HCV RNA rose 0.35 log at week 16 (95% CI 0.11-0.59) and 0.43 log at week 48 (95% CI 0.16-0.71).  When stratified by baseline CD4, HCV RNA increased 0.44 and 0.59 log at week 16 and 48 for subjects with entry CD4 < 350 (p < 0.04, p< 0.001), but only 0.26 and 0.1 log at week 16 and 48 for subjects with entry CD4 >350 (p=0.04, p=NS).  No correlation between HCV and HIV RNA was seen.  Baseline ALTs were grade 1 or 2 in 9 patients and grade 0 in the remainder.  While mean ALT levels rose from 51 to 75 at week 16, Grade 3+ ALT elevations occurred in only 2 patients without ART discontinuation. The case-control cohort showed no significant differences between HCV(+) and HCV(-) patients for baseline log₁₀HIVRNA (3.97 vs 3.70) and CD4 (470 vs 438). HCV coinfection had no effect on the overall mean CD4 increase at week 16 (+133 vs +100, p=NS) or week 48 (+137 vs +151, p=NS), and on HIV suppression rates.

Conclusions: In HCV-co-infected patients entering ACTG trials, successful immune recovery is associated with a persistent increase in HCV RNA; this effect is confined to persons with baseline CD4 <350. Hepatotoxicity was uncommon and did not stop ART. Contrary to earlier studies, HCV coinfection did not appear to antagonize CD4 response to HAART.