1. Previous SVR With Interferon-Based Therapy for HCV Lowers Risk of Hepatotoxicity in HIV/HCV-Coinfected Individuals on Antiretroviral Therapy Slideset on: Labarga P, Soriano V, Vispo ME, et al. Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients. J Infect Dis. 2007;196:670-676. This program is supported by educational grants from Jointly sponsored by Postgraduate Institute for Medicine and Clinical Care Options, LLC

2. clinicaloptions.com/hiv Previous Interferon-Based Therapy in HIV/HCV-Coinfected Individuals Background  Drug-related hepatic events common cause of morbidity and mortality in HIV-infected individuals on antiretroviral therapy –Exacerbated by HCV coinfection and/or extent of liver fibrosis  Interferon-based regimens standard therapy for treating HCV infection –Successful treatment leads to improved liver histology and better long- term clinical prognosis  Current study assessed whether sustained clearance of HCV infection following interferon-based treatment affects hepatic tolerability of antiretroviral therapy in HIV/HCV-coinfected individuals Labarga P, et al. J Infect Dis. 2007;196:670-676.

3. clinicaloptions.com/hiv Previous Interferon-Based Therapy in HIV/HCV-Coinfected Individuals Summary of Study Design Labarga P, et al. J Infect Dis. 2007;196:670-676.  HIV/HCV-coinfected individuals who received any full course of interferon- based therapy since 1992 identified in 2 large HIV clinics in Spain –Inclusion criterion: receipt of antiretroviral therapy after interferon treatment –Exclusion criteria: chronic hepatitis B infection or other concomitant liver illnesses  Clinical and laboratory measurements –Transaminase levels, CD4+ cell count, HIV-1 RNA, HCV RNA, and other main laboratory parameters measured every 3 months after completion of interferon- based therapy –Fibrosis measured by hepatic elastometry  6 months after completion of interferon-based therapy  SVR defined as undetectable HCV RNA sustained for  6 months after completion of interferon-based therapy  Variables associated with hepatic events assessed by univariate and multivariate logistic regression analysis

4. clinicaloptions.com/hiv Previous Interferon-Based Therapy in HIV/HCV-Coinfected Individuals Main Findings  33% of HIV/HCV-coinfected individuals achieved SVR following interferon- based therapy –Individuals with SVR demonstrated significantly less advanced fibrosis, hepatotoxicity, and grade 3/4 transaminase elevations vs those not attaining SVR Labarga P, et al. J Infect Dis. 2007;196:670-676. Parameter After Interferon-Based Therapy SVR (n = 43) No SVR (n = 89) P Value Infection with HCV genotype 3, n (%)26 (61)13 (15)<.001 Mean CD4+ cell count, cells/mm 3  SD620  271610  300.9 Mean transaminases, IU/L  SD  ALT 25  1068  46 <.001  AST 28  1263  43 <.001 Advanced liver fibrosis, n (%)6 (14)47 (53)<.001 Hepatotoxicity, %9.337.5<.001 Grade 3/4 ALT elevations, %6.927.3.007 Mean antiretroviral therapy duration, mos  SD21.6  10.518.2  10.9.1

5. clinicaloptions.com/hiv Previous Interferon-Based Therapy in HIV/HCV-Coinfected Individuals Main Findings (cont’d) Labarga P, et al. J Infect Dis. 2007;196:670-676.  Mean duration of antiretroviral therapy: 19.3  10.9 months  37 patients (28%) experienced 49 different hepatic events during antiretroviral therapy following HCV treatment –10 patients (27%) had symptomatic liver reactions but no grade 3/4 transaminase elevations –Overall incidence of hepatotoxicity in study population: 9.7 episodes per 100 patient-years (95% confidence interval: 7.2-12.4 episodes per 100 patient-years) –Longer duration of HAART in patients with hepatic events vs those without: 12.7 vs 21.7 months (P <.001)

6. clinicaloptions.com/hiv Previous Interferon-Based Therapy in HIV/HCV-Coinfected Individuals Other Outcomes  Factors significantly associated with experiencing a hepatic event in univariate analysis included lack of SVR, more advanced liver fibrosis, and use of certain antiretrovirals –Demographic characteristics, immune status, and transaminase levels after interferon therapy not different between individuals with or without a hepatic event  Of factors significantly associated with a hepatic event, only 4 significant in multivariate analysis Labarga P, et al. J Infect Dis. 2007;196:670-676. ParameterOdds Ratio (95% Confidence Interval)P Value Lack of SVR6.13 (1.83-37.45).003 Receipt of stavudine and/or didanosine 3.59 (1.23-10.42).02 Receipt of efavirenz0.13 (0.04-0.44).001 Receipt of PIs0.07 (0.02-0.20) <.01

7. clinicaloptions.com/hiv Previous Interferon-Based Therapy in HIV/HCV-Coinfected Individuals Summary of Key Conclusions  Individuals coinfected with HIV and HCV who achieved sustained virologic suppression of HCV RNA following interferon-based treatment experienced fewer hepatic events during antiretroviral therapy  Lack of HCV SVR and receipt of stavudine and/or didanosine independently associated with increased risk of hepatotoxicity  Receipt of PIs or efavirenz independently associated with decreased risk of hepatotoxicity Labarga P, et al. J Infect Dis. 2007;196:670-676.