Abstract 575 - A Comparison of Hepatotoxicity and Response to Potent Antiretroviral Therapy (ARV) in HIV/HCV-Infected and Matched HIV-Infected Patients.

575 A Comparison of Hepatotoxicity and Response to Potent Antiretroviral Therapy (ARV) in HIV/HCV-Infected and Matched HIV-Infected Patients.

F. J. Torriani*¹, C. Byrnes¹, V. Asensi², J. A. Carton², and J. A. Maradona².
¹Univ.of California San Diego, La Jolla and²Univ. of Oviedo Med. Sch., Spain.

Background:Hepatotoxicity (HTOX) after starting ARV occurs in up to 14% of HIV/HCV-coinfected patients (pts) and often leads to the interruption of ARV. Direct drug toxicity or immune recovery syndrome to HCV antigens are postulated mechanisms of HTOX. We characterized parameters of response to ARV and HTOX in HIV/HCV pts and compared them to HIV-infected (HIV) pts matched by age, year of starting ARV, and CD4 counts before ARV.

Methods:CD4 counts, HIV RNA, ALT, alkaline phosphatase (alk phosp), bilirubin (bili) and GGT pre-ARV, and changes at 1, 2, 6, 9, and 12 months (mo) post-ARV from 94 HIV/HCV pts and 94 HIV pts starting ARV between 7/96—12/99, were compared retrospectively. HTOX was defined as a rise in ALT >2-fold the upper limit of normal. Results are expressed as mean+SE.

Results:Pre-ARV CD4 counts were 266+15 cells/mm³and HIV RNA was 4.4+0.1 log₁₀copies/mL. ALT were significantly higher in HIV/HCV vs. HIV: 90+9 vs. 39+5 IU (P < 0.001). No HIV/HCV pt was treated for HCV prior or during ARV. Up to 1.5 years before ARV, 23 HIV/HCV and 30 HIV pts had an AIDS-defining event, while post-ARV only 5 and 1 experienced AIDS, respectively. 89% of HIV/HCV vs. 94% of HIV received a PI-containing regimen. Maximal CD4 and HIV RNA changes occurred within 2 mo and were less pronounced in HIV/HCV vs. HIV: +111 vs. 223 (P < 0.001) and -1.3 vs. -2.0 after 12 mo of ARV (P < 0.001). In 64/72 (88%) HIV/HCV and 55/80 (69%) HIV, HIV RNA was <400 copies/mL after 12 months of ARV. 37/94 (39%) HIV/ HCV vs. 10/94 (11%) HIV had >2-fold rise in ALT, leading to switches in 8 and cessation of ARV in 2 HIV/ HCV pts vs. none in HIV. Two HIV/HCV pts died of cirrhosis. While ALT >2-fold predominantly occurred 2—6 mo after ARV in HIV pts, HTOX was seen at all time points in HIV/HCV pts.

Conclusions:The magnitude of CD4 and HIV response to ARV is significantly less in HIV/HCV pts with similar CD4 and HIV RNA levels prior to ARV. HTOX correlated with immunologic and virologic response to ARV. HTOX is more frequent, severe, and sustained in HIV/HCV pts and may require changes in ARV.