1. ORGAN TRANSPLANTATION: PERSONS WITH DETECTABLE HIV VIRAL LOAD Margaret Ragni, MD University of Pittsburgh

2. HIV/HCV Co-Infected Patients Greater HCV RNA, liver fibrosis, ESLD l Increased hepatotoxicity, drug interactions l Reduced response to interferon/ribavirin l Reduced tolerance to HAART Thus, more likely to have detectable HIVviral load

3. HIV Viral Load: A Spectrum 1. HIV Disease Progression  HIV RNA  Disease Progression 2. HIV Transmission  HIV RNA  Sexual transmission 3. Survival  HIV RNA  Survival  Spectrum: Not Black and White

4. HIV Viral Load: A Spectrum 1. HIV Disease Progression – AIM is undetectable HIV RNA REALITY is low set point slows progression (Mellors et al, Science, 1996) 2. HIV Sexual Transmission – AIM is undetectable HIV RNA REALITY is low set point reduce transmission (Ragni et al, JAIDS, 1998) 3. Survival – AIM is undetectable HIV RNA REALTY is low set point improves survival (Mellors et al, Ann Int Med, 1996)  Spectrum: Not Black and White

5. LIVER TRANSPLANT in HIV: PITTSBURGH (1997-2001) Age//Sex Risk GroupOLTXCD4HIV RNAHAART SURVIVAL 1.38 yo WM Hemophilia9/97160 /  l <400 3TC, d4T, Viracept46 months HBV/HCV/HIV 2.44 yo WM Bisexual12/98169 /  l <50 3TC, d4T,Viracept31 months HCV/HIV 3.43 yo WM Hemophilia1/99155 /  l 16,000 Combivir,Viracept0.5 months HCV/HBV/HIVd. pancreatitis 4.43 yo WM Hemophilia3/9962 /  l <400 Combivir, Viracept 22 months HCV/HIVd. noncompli,rejex 5.40 yo BF Heterosexual5/00103 /  l 3,300 Combivir, Viracept14 months AHN/Viramune/HIV 6.52 yo WM IVDU10/00280 /  l <400 3TC, ddC, Crixivan9 months HBV/HCV/HIV 7.33 yo WM Hemophilia01/01350 /  l <400 Combivir, Viracept 6 months HCV/HBV/HIVViramune (pre)

6. RECOMMENDATIONS: OLTX Eligibility l Subjects with CD4 < 200/  l l Subjects with detectable HIVviral load – Previously responsive to HAART – No longer able to tolerate HAART l Liver toxicity l Severe liver dysfunction l Drug interactions l Subjects with past opportunistic infections – Otherwise as above, once infection resolves

7. Other Unanswered Questions 1. Optimal Time for OLTX 2. Optimal Antiretroviral, Antirejection Drugs 3. Recurrence of HCV Infection in Transplanted Organ

8. Issues: Transplant in HIV Infection 1. Develop new treatment approaches for HCV 2.Determine risk factors for HCV progression 3. Determine risk factors for adverse outcome

9. Issues: Transplant in HIV Infection 1. Develop new treatment approaches for HCV Antiviral, anti-cytokine, anti-fibrotic drugs 2.Determine risk factors for HCV progression ETOH, Hep B, HIV, Hepatotoxins 3. Determine risk factors for adverse outcome Pancreatitis, drug interactions, anti-rejection,antiretroviral drugs