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Optimizing Care for the HIV-Hepatitis Coinfected Patient

Optimizing Care for the HIV-Hepatitis Coinfected Patient. Mark Holodniy, MD Professor of Medicine Stanford University Stanford, California. Sponsored by The Academy for Continued Healthcare Learning. Supported by an educational grant from Abbott . Intended Audience

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Optimizing Care for the HIV-Hepatitis Coinfected Patient

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  1. Optimizing Care for the HIV-Hepatitis Coinfected Patient Mark Holodniy, MD Professor of Medicine Stanford University Stanford, California Sponsored by The Academy for Continued Healthcare Learning Supported by an educational grant from Abbott

  2. Intended Audience This activity is intended for HIV specialists from a wide range of disciplines, including but not limited to internal medicine, family practice, and infectious disease physicians. Pharmacists, nurses and other healthcare professionals focusing on HIV care are also encouraged to attend. In accordance with PhRMA guidelines, this program is intended for healthcare professionals only. Activity Purpose To update physicians, pharmacists, nurses and other health care professionals, on recent advances in HIV research and the management of HIV infectious disease. Method of Participation This activity will consist of a lecture meeting with collateral slides, syllabus, and interactive question and answer session.

  3. Accreditation • The Academy for Continued Healthcare Learning (ACHL) is accredited by the • Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. • Designation • The Academy for Continued Healthcare Learning (ACHL) designates this • educational activity for a maximum of 1.0 AMAPRA Category 1 CreditTM. • Physicians should only claim credit commensurate with the extent of their • participation in the activity. • The Academy for Continued Healthcare Learning (ACHL) is accredited by the • Accreditation Council for Pharmacy Education (ACPE) as a provider of • continuing pharmacy education. In order to receive credit, pharmacists must complete the activity requirements and evaluation at the conclusion of the program. This activity has been approved for a maximum of 0.1 CEU. • ACPE Universal Program Number (UPN): 396-000-06-013-L02 • Initial Release Date: 01/20/06 • The Academy for Continued Healthcare Learning (ACHL)has been • reviewed and approved as an Authorized Provider by the International Association of Continuing Education and Training (IACET). ACHL hasawarded 0.1 CEUto participants who successfully complete this program. IACET CEU credit may be used toward nursing credits. Contact your local accrediting body for details.

  4. Disclosure Statements The Academy for Continued Healthcare Learning (ACHL) requires that the faculty participating in a CME/CE activity disclose to the participant any relevant affiliation or other financial relationship (1) with the manufacturers of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation, and (2) with any commercial supporters of the activity. The ACHL also requires participating faculty to disclose when unapproved/unlabeled uses of a product are discussed in a CME/CE activity. MarkHolodniy, MD, has no relevant affiliations or financial relationships to disclose. The ACHL staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose.

  5. Disclaimer • The content for this activity was developed independently of the commercial supporter. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor. • This educational activity was planned and produced in accordance with the ACCME Essential Areas and Elements, Policies, and Standards for Commercial Support as well as the ACPE Criteria for Quality and Interpretive Guidelines. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection and analysis. • Participants are advised that one or more presentations in this CME/CE activity may contain references to unapproved or unlabeled uses of drugs or devices. Participants should note that the use of these agents outside current approved labeling is considered investigational and are advised to consult current prescribing information for these products.

  6. Housekeeping Information • Please refer to the syllabus for complete CME/CE credit information • Please return your completed enrollment/evaluation forms to the Meeting Host before you leave • Please turn your cell phones to off or vibrate

  7. Learning Objectives Upon completion of this activity, participants should be able to Describe liver-related adverse events in HIV-Hepatitis coinfected patient Examine associated hepatotoxicity with different treatment modalities Review treatment options, taking into consideration hepatic safety

  8. Liver-Related Adverse Events • Liver-related adverse events are the most common grade 4 adverse events in HIV positive patients • Hospitalizations for liver related events are more common than hospitalizations for opportunistic infections or for IDU related events • Liver toxicity of ARV agents should be seriously considered before initiating therapy

  9. Most Common Grade 4 Events:CPCRA Cohort Liver 2.6 Incidence Neutropenia 1.5 per 100 Person-Years Anemia 1.1 CVD 0.9 Pancreatitis 0.9 Psychiatric 0.8 Renal 0.6 Hazard Ratio For Death by Grade 4 Event (95% CI) 3.49 (2.38-5.12) P=.0001 1.76 (0.99-3.09) P=.051 7.08 (4.15-12.05) P=.0001 3.40 (1.82-6.33) P=.0001 1.91 (0.79-4.63) P=.15 1.02 (0.61-1.72) P=.93 4.60 (2.45-8.66) P=.0001 N=2947; CPCRA=Terry Beirn Community Programs for Clinical Research on AIDS. Reisler RB, et al. JAIDS. 2003;34:379-386.

  10. Prevalence of HIV/HCV Coinfection HIV/HCV Coinfection Prevalence by Risk Factor • Johns Hopkins HIV clinic • Urban setting • Prospective, longitudinal database • HCV-coinfection clinic established in 1997 • 1742 HIV-infected patients screened for HCV infection (1997-2000) • HCV+: 798 patients Prevalence of Antibody HCV+, % IDU Hetero- Homo- Entire sexual sexual Cohort Sex Sex Sulkowski MS, et al. Hepatology. 2000;32. Abstract 204.

  11. Impact of HIV Infection onHBV and HCV Disease Progression • Impact of HIV infection • Accelerates the course of HBV and HCV infection • Liver disease associated with HBV or HCV infection • A leading cause of morbidity and mortality among HIV-infected patients HBV or HCV Disease Course HBV or HCV Infection 15% 85% Recovery Chronic 68% 17% Stable Cirrhosis 13% 4% Slowly Progressive HCC ESLD Thomas DL, et al. JAMA. 2000;284:450-456. Benhamou Y, et al. Hepatology. 1999;30:1054-1058. Graham CS, et al. Clin Infect Dis. 2001;33:562-569. Bodsworth NJ, et al. J Infect Dis. 1991;163:1138-1140. Gilson RJ, et al. AIDS. 1997;11:597-606. HCC=hepatocellular carcinoma.ESLD=end-stage liver disease.

  12. Rapid Progression of Liver Disease in HIV/HCV Coinfected Patients • Prospective study of fibrosis progression in 67 coinfected patients • 2 biopsies, median time between biopsies was 2.84 years Patients With Mild Fibrosis (≤F1) on First Biopsy >25% of patients with mild fibrosis on initial biopsy had ≥2 stage progression in fibrosis score Change in Ishak Score From First to Second Biopsy Sulkowski M, et al. 12th CROI. Boston. 2005. Oral abstract 121.

  13. Survival of Patients Coinfected WithHIV and Hepatitis B or C Virus HIV or Liver Mortality • Cohort study • 472 HIV patients followed for 8343 patient-months • HIV alone (n=126) • HIV/HBV (n=72) • HIV/HCV (n=256) • HIV/HBV/HCV (n=18) • Variables associated with liver death in the cohort coinfected with HCV, HBV, or both (n=346) • 0 to 2 antiretroviral drugs • CD4 <200 cells/µL Mortality, % HIV HIV/HBV HIV/HCV HIV HBV/HCV Bonacini M, et al. AIDS. 2004;18:2039-2045.

  14. Association Between CD4 Cell Count and Liver-Related Death • D:A:D Study • Prospective study with 23 441 people with HIV • 1248 deaths between 2000-February 2004 • Leading causes of death: • AIDS, 30% • Liver-related death 14% (79% associated with chronic hepatitis) • Heart disease 9% • Non-AIDS malignancies, 8% • Relative risk of death for persons with CD4 <50 cells/mm3 as compared with persons with CD4 >500 cells/mm3 Weber, R, et al. 12th CROI. Boston. 2005. Abstract 595.

  15. HAART and the Impact of HIV RNA, CD4, or Both on Liver Fibrosis 0.196 P=.005 P=.005 P=.04 0.162 0.155 0.145 P=.005 0.123 0.122 0.121 Ishak Fibrosis Units/Year <400 400-99K ≥100K ≥350 <350 <400 ≥400 CD4 (cells/mm3) HIV RNA (copies/mL) HIV RNA (copies/mL) + <500 CD4 cells/mm3 Brau N, et al. 39th EASL. Berlin, 2004. Abstract 99.

  16. HAART and Liver Fibrosis in HIV/HCV Coinfected Patients • HAART may slow fibrosis progression • HIV/HCV coinfection versus HCV monoinfection post-HAART: No difference in: • Fibrosis progression rate (P=.29) • Fibrosis stage (P=.87) • Necroinflammatory grade (P=.89) • Fibrosis progression rate (FPR) in Coinfected patients: • Strongly correlated with HIV RNA levels • Coinfected patients with any HIV RNA >400 copies/mL had a faster FPR than coinfected patients with HIV RNA <400 copies/mL (P=.004) • Coinfected patients with HIV RNA <400 copies/mL had a similar FPR to HCV monoinfected patients (P=.253) • Increased with CD4 cell counts <500 cells/mm3 combined with HIV RNA >400 copies/mL (P=.005) Brau N, et al. 39th EASL. Berlin, 2004. Abstract 99.

  17. Overall Mortality HAART* Cumulative Survival ART No therapy *P<.001 0 1000 2000 3000 4000 5000 6000 Days Liver-Related Mortality HAART* ART No therapy Cumulative Survival *P=.018 0 1000 2000 3000 4000 5000 6000 Days Impact of HAART and ART on Mortalityin HIV/HCV Coinfected Patients • Bonn cohort (1990-2002) • 285 HIV/HCV coinfected patients • Liver-related mortality rates per 100 person-years • HAART: 0.45 • ART: 0.69 • No therapy: 1.70 • Predictors for liver-related mortality • No HAART • Low CD4 cell count • Increasing age Qurishi N, et al. Lancet. 2003;362:1708-1713.

  18. Summary: Clinical Implications of Liver Damage and Benefits of HAART in Coinfected Patients • Liver damage in HIV-infected patients causes significant morbidity and mortality • HIV infection accelerates the course of viral hepatitis • Patients with low CD4 cell counts have an increased risk of liver-related death • HAART • Can be tolerated by coinfected patients • Controls HIV • May slow the progression of fibrosis, especially PIs • Improves immune status • Improves survival

  19. Balancing HAART and Hepatic Safety NRTIs

  20. NRTI-Related Hepatotoxicity • Syndrome of mitochondrial toxicity • Mitochondria have their own DNA (mtDNA) that encodes 13% of mitochondrial proteins • NRTIs inhibit mitochondrial DNA synthesis, causing mitochondrial dysfunction and cellular toxicity • High-risk drugs • Stavudine, didanosine, zalcitabine • Low-risk drugs • Abacavir, zidovudine, lamivudine Fleischer R, et al. Clin Infect Dis. 2004;38:e79-e80.

  21. Association of Dideoxynucleoside Analogues With Hepatic Steatosis • Retrospective chart review of 179 HIV/HCV coinfected patients • Univariate analysis • Factors associated with steatosis; Dideoxynucleosides (P=.029) and the number of nucleoside analogues (P=.042) • Use of protease inhibitors was not associated with steatosis • Multivariate analysis McGovern B, et al. 12th CROI. Boston. 2005. Abstract 950.

  22. Balancing HAART and Hepatic Safety NNRTIs

  23. NNRTI-Related Hepatotoxicity • Incidence of ALT or AST elevations in randomized trials • Grade 3 (>5 x ULN) and 4 (>10 x ULN): 8% to 16% • Hepatitis coinfection increases the risk of hepatotoxicity • Nevirapine • Fatal hepatic necrosis • US FDA “warning” Sulkowski MS, et al. Hepatology. 2002;35:182-189. Reisler R, et al. 1st IAS Conference. Buenos Aires, 2001. Abstract 43. Stern J, et al. JAIDS. 2003;34(suppl 1):S21-S33. Wit FW, et al. J Infect Dis. 2002;186:23-31. van Leth F, et al. Lancet. 2004;363:1253-1263. Gallant JE, et al. JAMA. 2004;29:191-201.

  24. Risk Factors for Severe, Life-Threatening Hepatotoxicity With Nevirapine • Women with CD4 cell counts >250 cells/mm3 • Have a 12-fold higher risk versus women with <250 cells/mm3 • Can be fatal • Greatest risk of severe and potentially fatal hepatic events often associated with rash • Occurs in first 6 weeks of nevirapine therapy • Close monitoring recommended. In some cases, hepatic injury progresses despite discontinuation of treatment • Nevirapine should not be used for chronic therapy among women with CD4 >250 cells/mm3 when other options exist Viramune [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2005.

  25. Meta-Analysis of AACTG Studies:Odds Ratio of Severe Hepatotoxicity • Retrospective analysis of 21 AACTG studies • 9003 patients • Single and double NRTIs • Triple regimens including NRTIs, NNRTIs, and PI • Overall incidence • Severe hepatotoxicity: 10% • 23% discontinued due to severe hepatotoxicity • Liver-related mortality: 0.3% • NRTI-based regimen: 0.46% • NNRTI or PI-based regimen: 0.13% Grade 3 or 4 elevations (>5 x ULN). Reisler R, et al. 1st IAS Conference. Buenos Aires. 2001. Abstract 43.

  26. 2NN Study: Severe Hepatotoxicity in Patients Receiving NNRTI-Based Regimens • Treatment-naïve patients • 1216 enrolled • HBV coinfected: 5.2% • HCV coinfected: 9.5% • NNRTI + d4T + 3TC • Nevirapine qd (400 mg) • Nevirapine bid (200 mg) • Efavirenz qd (600 mg) • Nevirapine + efavirenz qd (400 + 800 mg) • 2 nevirapine-attributed deaths • Fulminant hepatitis, pancreatitis, renal failure • Stevens-Johnson syndrome (recovered) • Later developed septicemia due to a methicillin-resistant Staphylococcus aureus infection Grade 3/4 Hepatotoxicity 13.6% 9.1% 8.3% Patients, % 4.5% QD BID Efavirenz Efavirenz + (n=220) (n=387) (n=400) Nevirapine (n=209) Nevirapine van Leth F, et al. Lancet. 2004;363:1253-1263.

  27. Efavirenz-containing regimens Indinavir + 2 NRTIs Study 006: Patients WithHepatitis C and/or Hep B Coinfection • Seropositive for hepatitis B and C at study entry • 137 patients treated with efavirenz-containing regimens • 84 patients treated with indinavir + 2 NRTIs • Discontinuations due to liver or biliary system disorders were similar (2% to 3%) ALT and AST >5 Times ULN 20% 13% Patients (%) 7% 7% ALT AST Sustiva [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2003.

  28. Summary of NNRTIs and Hepatic Safety • There appears to be a modest class effect of NNRTIs on abnormal liver enzyme levels • Rate of serious clinical (symptomatic) hepatotoxicity, ALT and/or AST levels >5 times ULN is relatively low • May be significantly higher in patients coinfected with HBV or HCV • Unique hepatic event associated with nevirapine • Immune-mediated • Associated with rash • Occurs almost exclusively within the first 6 weeks of nevirapine treatment

  29. Balancing HAART and Hepatic Safety PIs

  30. PI-Related Hepatotoxicity • Incidence of ALT and/or AST elevations in registration trials • Grade 3 (>5 x ULN) and 4 (>10 x ULN): 1% to 9% • Full-dose ritonavir • Only PI identified as an independent risk factor for severe hepatic injury • Boosting doses of ritonavir (≤200 mg/d) • Not associated with significantly higher incidence of severe hepatotoxicity versus other PIs • Less data on newer PIs • Atazanavir or fosamprenavir Sulkowski MS, et al. Clin Infect Dis. 2004:38(suppl 2):S90-S97.

  31. Incidence and Risk Factors of HAART-Associated Hepatotoxicity • Retrospective cohort analysis (n=560) • Risk factors for grade 4 liver enzyme elevations (HR [95% CI]) • Female sex: 2.8 [1.3-5.8] • Baseline ALT levels (per 10 U/L increase): 1.05 [1.01-1.11] • Chronic HCV infection: 5.0 [2.3-10.7] • Chronic HBV infection: 9.2 [4.1-20.6] • Recent discontinuation of lamivudine: 6.8 [2.1-22.7] • Recent start of nevirapine:* 9.6 [3.2-28.3] • Recent start of full-dose ritonavir:* 4.9 [2.0-12.1] • No increased risk if ritonavir dose ≤200 mg bid *12-week period after start of drug. †Patients without NRTIs experience using first-line ARV versus subsequent regimens. Wit FW, et al. J Infect Dis. 2002;186:23-31.

  32. Hepatotoxicity Associated with PI-Based Regimens ± Low-Dose Ritonavir: Design • Prospective study (n=1161) • Evaluate grade 3/4 AST/ALT elevations of PIs • Median follow-up: 211−365 days • Baseline characteristics • Age*: 37 years • Male: 73% • African American: 77% • HCV+: 46% • HbsAg+: 10% • ALT*: 30 IU/L • CD4*: 168 cells/mm3 • HIV RNA*: 4.7 log10 copies/mL 1st PI-Containing Regimen Nelfinavir Saquinavir/r Indinavir/r Indinavir Lopinavir/r *median Sulkowski MS, et al. Hepatology. 2003;38:698A. Sulkowski MS, et al. AIDS. 2004;18:2277-2284.

  33. Risk Factors for PI-AssociatedDrug-Induced Liver Injury • No increased risk observed with lopinavir/r and nelfinavir • Results consistent with data from the randomized control trial by Walmsley (Study 863) • HIV/HCV-coinfected patients • 84% had no drug-induced liver injury Multivariate analysis Sulkowski MS, et al. Hepatology. 2003;38:698A. Sulkowski MS, et al. AIDS. 2004;18:2277-2284.

  34. Study 863: 60-Week Safety of Lopinavir/r and Nelfinavir by Hepatitis Status • Hepatitis B/C-positive patients • Patients with ALT/AST >3x ULN were excluded at screening regardless of hepatitis status • Lopinavir/r patients (n=57) tended to have a lower incidence of grade 3/4 AST and ALT elevations compared with nelfinavir-treated patients (n=68) • AST: lopinavir/r 4% versus nelfinavir 13% • ALT: lopinavir/r 12% versus nelfinavir 17% • Similar incidence of discontinuations due to hepatic adverse events in both groups (4%) • No discontinuations due to elevated liver enzymes in either group • No hepatic-related events resulted in death Bernstein B, et al. 1st IAS Conference. Buenos Aires. 2001. Abstract 525.

  35. Study 863: Selected Adverse Events and Laboratory Abnormalities *P<.05 and †P<.001 vs hepatitis positive Bernstein B, et al. 1st IAS Conference. Buenos Aires. 2001. Abstract 525.

  36. Study 863: Demographics of HIV/HCV Coinfected Patients All patients received lamivudine + stavudine. HCV Genotype 1: 71% of patients. Sherman KE, et al. 11th CROI. San Francisco. 2004. Abstract 811.

  37. Study 863 HIV/HCV-Coinfected Patients: CD4 Cell Counts Through 48 Weeks On-Treatment 234 Lopinavir/r + d4T + 3TC Nelfinavir + d4T + 3TC 184 CD4 Change From Baseline (cells/mm3) P=0.247 0 8 16 24 32 40 48 LPV/r (n=29) (n=23) (n=20) Nelfinavir (n=41) (n=34) (n=35) Weeks Sherman KE, et al. 11th CROI. San Francisco. 2004. Abstract 811.

  38. Study 863 HIV/HCV-Coinfected Patients: Time to HIV RNA <400 and <50 Copies/mL HIV RNA <400 Copies/mL HIV RNA <50 Copies/mL 100% 87% 100% 73% Lopinavir/r (n=29) Nelfinavir (n=41) Patients, % Patients, % Lopinavir/r (n=29) Nelfinavir (n=41) First evaluated at 24 weeks P=.274 P=.308 Weeks Weeks All patients received lamivudine + stavudine. Sherman KE, et al. 11th CROI. San Francisco. 2004. Abstract 811.

  39. Study 863 HIV/HCV-Coinfected Patients:Mean ALT Through 48 Weeks On-Treatment † * 63 * Mean ALT, IU/L 44 Lopinavir/r + d4T + 3TC Nelfinavir + d4T + 3TC 0 8 16 24 32 40 48 LPV/r (n=29) (n=24) (n=21) Nelfinavir (n=41) (n=37) (n=35) Weeks *P<.05 and †P<.01 vs LPV/r. Sherman KE, et al. 11th CROI. San Francisco. 2004. Abstract 811.

  40. Meta-Analysis of Lopinavir/Ritonavir Efficacy in HIV/HCV Coinfected Patients • 48-week exposure data from 8 clinical trials • 819 adult HIV-infected patients • Hepatitis positive: 132 patients with HCV and/or HBV coinfection • Hepatitis negative: 687 patients • 5-year exposure data from Study M97-720 • Lopinavir/ritonavir • At least as safe as nelfinavir • 6.9% to 12.8% experienced grade 3+ ALT elevations • Overall coinfected patients did have 3 to 4 fold higher risk of ALT and AST elevations versus those without hepatitis da Silva, et al. 15th IAC. Bangkok, 2004. Abstract MoPeB3285.

  41. Treatment-Naïve Treatment-Experienced Hepatitis negative (n=433) Hepatitis positive (n=75) Hepatitis negative (n=254) Hepatitis positive (n=57) HIV RNA <400 copies/mL, % HIV RNA <400 copies/mL % P=0.562 P=0.205 0 8 16 24 32 40 48 0 8 16 24 32 40 48 Week Week Meta-Analysis: Virologic Outcomes With Lopinavir/Ritonavir All patients received lamivudine + stavudine. da Silva, et al. 15th IAC. Bangkok, 2004. Abstract MoPeB3285.

  42. Treatment-Naïve Treatment-Experienced P=.69 P=.17 219 211 114 CD4 Change, cells/mm3 CD4 Change, cells/mm3 82 Hepatitis Positive (n=39) Hepatitis Negative (n=181) Hepatitis Positive (n=51) Hepatitis Negative (n=377) Meta-Analysis: Week 48 CD4 Cell Gain With Lopinavir/Ritonavir by Hepatitis Status All patients received lamivudine + stavudine. da Silva, et al. 15th IAC. Bangkok, 2004. Abstract MoPeB3285.

  43. Meta-Analysis Findings • A higher percentage of HIV/HCV coinfected patients treated with lopinavir/ritonavir maintained HIV RNA levels <400 and <50 copies/mL compared with nelfinavir-treated patients • Lopinavir/ritonavir appears at least as safe as nelfinavir in HIV/HCV coinfected patients • A minority of patients (6.9% to 12.8%) experienced grade 3+ ALT elevations • Lopinavir/ritonavir appears to be equally effective against HIV infection in HCV positive and negative patients da Silva, et al. 15th IAC. Bangkok, 2004. Abstract MoPeB3285.

  44. Study 418: HIV RNA <50 Copies/mL Through Week 48 by Baseline Hepatitis Status (ITT NC=F) Easterbrook P. et al. HIV7. Glasgow, UK. 2004. Abstract 164.

  45. Study 418: CD4 Count Mean Change From Baseline by Baseline Hepatitis Status Easterbrook P. et al. HIV7. Glasgow, UK. 2004. Abstract 164.

  46. Study 418 Incidence of Resistance Through Week 48 LPV/r 800/200 mg QD (n=115) LPV/r 400/100 mg BID (n=75) Patients eligible for resistance testing1 Genotypic results available Lopinavir resistance2 Tenofovir resistance3 Emtricitabine resistance4 11 8/11 0/8 0/8 2/8 11 7/11 0/7 0/7 1/7 1HIV RNA >500 copies/mL any time during Weeks 12-24. All samples >500 copies/mL were submitted for testing 2LPV/r resistance: emergence of primary or active site mutation at protease positions 8, 30, 32, 46, 47, 48, 50, 54, 82, 84, 90, with phenotypic LPV resistance FC > 2.5 vs WT 3TDF resistance: emergence of K65R or any TAM (41, 67, 70, 210, 215, 219) in RT 4FTC resistance: emergence of M184V mutation in RT Molina JM, et al. XV IAC. Bangkok, Thailand. 2004. Abstract WePe5701.

  47. Summary of PIs and Hepatic Safety • Rate of serious clinical (symptomatic) hepatotoxicity, ALT and/or AST levels >5 times ULN is relatively low • Boosting doses of ritonavir not associated with significantly higher incidence of severe hepatotoxicity versus other PIs • Patients coinfected with HBV and/or HCV • Greater risk of hepatotoxicity • Lopinavir/ritonavir appears at least as safe as nelfinavir • Boosted PIs can help suppress resistance to other ARV agents • More data for atazanavir and fosamprenavir are needed in this patient population

  48. Conclusions

  49. Conclusions • High prevalence of HIV-hepatitis coinfection • HIV RNA and CD4 are correlated with fibrosis progression in coinfected patients • Use of NNRTIs is associated with increased risk of hepatotoxicity • For PI regimens, no increased risk if ritonavir dose <200 mg bid

  50. Conclusions, cont. • Patients treated with boosted PIs tend to have a lower incidence of grade 3/4 AST and ALT elevations than patients treated with nelfinavir • Boosted PIs tend to suppress HIV RNA better than nelfinavir in HIV/HCV coinfected patients • Boosted PIs can help suppress resistance to other ARV agents (eg, tenofovir DF)

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