1. 2005 Asilomar HIV/AIDS Medical Update David H. Spach, MD Clinical Director, Northwest AIDS Education and Training Center Professor of Medicine, Division of Infectious Diseases University of Washington, Seattle DHS/PP

2. HIV/AIDS: 2005 Antiretroviral Therapy Update Hepatitis C & HIV Co-Infection Update Hepatitis B & HIV Co-Infection Update New Antiretroviral Guidelines New Medications Future Medications DHS/PP

3. HCV and HIV Co-Infection Update DHS/PP

4. HCV Therapy: Terminology DHS/PP Treatment (48 Weeks) Post-Treatment (24 Weeks) End of Treatment Response (ETR) HCV RNA undetectable Early Virologic Response (EVR) HCV 2 log Sustained Virologic Response (SVR) HCV RNA undetectable Week 12Week 48Week 72Week 0

5. Case History: HCV Rx A 38-year-old HIV and HCV co-infected man is evaluated for treatment of HCV. Labs - CD4 cell count 486 cells/mm 3 (on no ARV Rx) - HCV genotype 1 - HCV RNA level of 2,000,000 copies/ml - Liver Bx: Metavir Stage 3 fibrosis What would be the preferred therapy for his hepatitis C? 1. Interferon + Ribavirin x 24 weeks 2. Peginterferon + Ribavirin x 24 weeks 3. Peginterferon + Ribavirin x 48 weeks 4. Peginterferon + Ribavirin x 96 weeks DHS/PP

6. Progression of HCV Treatment Success Sustained Virologic Response From: Strader DB, et al. Hepatology 2004;39:1147-71. DHS/PP

7. Treatment of HCV in HIV-Infected Persons APRICOT TRIAL (“Pegasys”)  Background - N = 868 - All with baseline biopsy  Evaluation - SVR: HCV RNA <50 IU/ml at week 72  Regimens (48 Weeks of Therapy) - INF alpha-2a + Ribavirin - PEG-IFN alpha-2a - PEG-IFN alpha-2a + Ribavirin Study Design SVR: 24 Week Post-Treatment From: Torriani FJ, et al. N Engl J Med 2004;351:438-50. DHS/PP Dosing - Interferon alpha-2a: 3 million IU sq 3x/week - Peginterferon alpha-2a: 180 ug sq q week - Ribavirin: 800 mg PO qd

8. Treatment of HCV in HIV-Infected Persons ACTG A5071 Study (“Pegasys”)  Background - N = 133 - All with baseline biopsy  Evaluation - SVR: HCV RNA < 60 IU/ml at week 72  Regimens (48 Weeks of Therapy) - INF alpha-2a + Ribavirin - PEG-IFN alpha-2a + Ribavirin Study Design SVR: 24 Week Post-Treatment From: Chung R, et al. N Engl J Med 2004;351:451-9. DHS/PP Dosing - Interferon alpha-2a: 6 million IU sq 3x/week x 12 weeks, then 3 million IU sq 3x/week - Peginterferon alpha-2a: 180 ug sq q week - Ribavirin: 800 mg PO qd

9. Results of HCV & HIV Co-Infection Treatment Trials Peginterferon + Ribavirin x 48 Weeks DHS/PP Peginterferon-2a Peginterferon-2b

10. Case History: HCV Rx The patient (HCV Genotype 1) is started on Peginterferon alpha-2b plus Ribavirin. His 12 week HCV RNA level is 1,300,000 copies/ml (baseline pretreatment HCV RNA was 2,000,000). What can we predict regarding the sustained virologic response (SVR) based on this 12 week HCV RNA value? 1. The 12 weak early virologic response (EVR) does NOT reliably predict SVR in HIV-infected patients 2. He has approximately a 30% chance of having a SVR 3. He has approximately a 15% chance of having a SVR 4. He has less than 10% chance of having a SVR DHS/PP

11. 12 Week Early Virologic Response (EVR) Predicts SVR APRICOT TRIAL (“Pegasys”) From: Torriani FJ, et al. N Engl J Med 2004;351:438-50. DHS/PP 12 Week EVR - HCV RNA 2 log

12. Case History: HCV Rx A 34-year-old HIV and HCV co-infected woman is evaluated for treatment of HCV. Labs - CD4 cell count 510 cells/mm 3 (on no ARV Rx) - HCV genotype 3 - HCV RNA level of 1,860,000 copies/ml - Liver Bx: Metavir Stage 3 fibrosis What would recommend for therapy in this HIV-infected patient with HCV genotype 3? 1. Peginterferon + Ribavirin x 12 weeks 2. Peginterferon + Ribavirin x 24 weeks 3. Peginterferon + Ribavirin x 48 weeks 4. Peginterferon + Ribavirin x 72 weeks DHS/PP

13. Peginterferon + Ribavirin for HCV Genotypes 2 or 3 48 Weeks versus 28 Weeks (Romance 2 Trial)  Background - N = 128 - HCV & HIV Co-Infected - All with HCV genotype 2 or 3 - CD4 > 200 and HIV RNA < 10,000  Regimen - Peginterferon alpha-2a + Ribavirin  Evaluation - Week 24: HCV RNA (57% HCV RNA -) - Those with (-) HCV RNA randomized to stop therapy or receive 24 more weeks Study Design SVR: 24 Week Post-Treatment From: Zanini B, et al. 3rd IAS Path & Treatment. 2005: MoPpLB0103. DHS/PP

14. Case History: HCV Rx A 29-year-old HCV and HIV co-infected woman is started on Peginterferon alpha-2a (180 ug sq once weekly) plus Ribavirin (400 mg bid) for HCV genotype 1. After 6 weeks of therapy, her Hb decreases from 14 to 10 g/dL. All other labs without a significant change. She weighs 71 kg. What would you recommend doing regarding the patient’s development of anemia? 1. No change needed; Hb likely will improve in next 4 weeks 2. Decrease ribavirin dose to 600 mg 3. Start recombinant erythropoetin 40,000 units sq weekly 4. Decrease Peginterferon to 150 uq sq once weekly DHS/PP

15. Ribavirin Dosing During Therapy Impact of Ribavirin Dosing on SVR - Near or optimal ribavirin dose associated with better SVR Ribavirin Target Dosing - Dose > 800 mg/d OR > 10.6 mg/kg/d - Most critical in first 20 weeks Use Recombinant Erythropoeitin/Epotin Alpha (Epogen;Procrit) - Initiate for Hb < 12 g/dL - Dose: 40,000 sq 1 x/w & increase to 60,000 sq/w if needed DHS/PP

16. HCV Therapy: Future Needs Improved Initial Response Rates with Genotype 1 Better Tolerated Therapy - Viramidine (Ribavirin prodrug); less anemia - Peptide aptemers (Inhibit HCV NS3 serine protease) Less Frequent Injections - Albumin Interferon Therapies for Peginterferon + Ribavirin Non-Responders - Maintenance PEG-INF - Valopictadine (NM 283) + PEG-INF? DHS/PP

17. DHS/Viral/PP Viramidine Adenosine Deaminase NH3 Liver Ribavirin Inactive Metabolite ICN3297 Adenosine Deaminase

18. Case History: HCV Rx & Interaction with ARV Meds Which of the following is TRUE regarding treatment of HCV in a HIV-infected person taking antiretroviral therapy? 1. Stavudine will increase ribavirin levels and increase the severity of anemia. 2. Ribavirin will increase the intracellular concentration of didanosine’s active metabolite and thus increase the risk of didanosine-related toxicity. 3. Didanosine will increase interferon levels and increase the degree of leukopenia. 4. Lopinavir-ritonavir is contraindicated in persons on peg- interferon because of the increased risk of hepatotoxicity. DHS/PP

19. Ribavirin and Didanosine Interaction DHS/PP

20. HBV and HIV Co-Infection Update DHS/PP

21. HIV/HBV: Initiating HBV Therapy A 36-year-old caucasian man with HIV and HBV co-infection: CD4 520, VL 18,000; Never on HAART. Persistent 3-5x increase in ALT/AST levels. HBsAg+; HBeAg+; HBV DNA: 6 x 10 8 IU/ml. Liver biopsy not performed Which of the following drugs has significant activity against Hepatitis B virus but NOT HIV? 1. Entecavir (Baraclude) 2. Ribavirin (Rebetol, Copegus) 3. Emtricitabine (Emtriva) 4. Valacyclovir (Valtrex) DHS/HIV/PP

22. DHS/HBV/PP FDA-Approved Therapies for HBV Infection DrugApprovalDose in HIV-Infected Patients Interferon-alpha-2b1991 *5-6 x 10 6 U sq qd or 9-10 x 10 6 U sq 3x/week Peginterferon-alpha 2a2005180 ug sq qweek x 48 weeks Lamivudine1998100 mq PO qd Adefovir200210 mg PO qd Entecavir20050.5-1.0 mg PO qd *Dose given for HBeAg+ (duration 4-6 months) Dose for HBeAg(-): 5-6 x 10 6 3x/week x 48 weeks

23. DHS/HBV/PP Non FDA-Approved Therapies for HBV DrugStatusDose Tenofovir300 mg PO qd Emtricitabine200 mg PO qd Peginterferon alpha 2b 1.5 ug/kg sq qweek (max 100 ug sq qweek)

24. DHS/HIV/AIDS/PP Entecavir (Baraclude) Classification: nRTI (guanosine analogue) Active against HBV: wild-type & Lamivudine-resistant Dosing - 0.5 mg and 1.0 mg tablets - Initial Rx: 0.5 mg PO qd - Lamivudine-resistant/failure: 1.0 mg PO qd Efficacy: Improves liver histology & degree of fibrosis Adverse Effects: flare of hepatitis when drug stopped HIV Activity: Entecavir does not have activity against HIV

25. Peginterferon-alpha-2a vs Lamivudine vs Both HBeAg-Negative Chronic HBV  Methods - N = 537 adults - HBeAg(-), chronic HBV  Regimens (48 Weeks of Therapy) - PegINF-alpha-2a: 180 ug qweek - Lamivudine: 100 mg PO qd - PegINF-alpha-2a + Lamivudine  Major Measurements - Virologic: HBV DNA < 20,000 - Biochemical: Normalization of ALT - Loss of HBsAg Study DesignResponse: 24 Weeks Post Rx From: Marcellin P, et al. N Engl J Med 2004;351:1206-17.

26. HIV/HBV: Initiating HBV Therapy The following 3 patients are co-infected with HBV and HIV. All 3 patients have HBsAg(+), persistent elevations of ALT (> 2-3x), and HBV DNA levels > 10 6. None of the patients have ever received ARV Rx or HBV Rx. Regarding treatment, assume they are willing, able, and adherent. Patient 1: CD4 490, HIV RNA=23,000; HBeAg(+). Patient 2: CD4 524; HIV RNA=38,000; HBeAg(-). Patient 3: CD4 210; HIV RNA = 112,000; HBeAg(+). Question How would you approach treatment of HBV infection is these 3 patients? DHS/HIV/PP

27. Chronic HBV & HIV: Initiating HBV Therapy Recommendations from an International Panel DHS/HIV/PP HBeAg (+) No Yes Peginterferon Yes Tenofovir plus Lamivudine (or Emtricitabine) plus NNRTI or PI No Entecavir or Adefovir HIV ARV Indicated From: Soriano V, et al. AIDS 2005;19:221-40.

28. HIV/HBV: Monitoring Response A 41-year-old woman with HIV and HBV co-infection: CD4 220, VL 88,000; Never on HAART. Labs show 3-4x increase in ALT/AST levels. HBsAg(+); HBeAg(+); HBV DNA: 4 x 10 9 IU/ml. Started on Tenofovir-DF + Lamivudine + Efavirenz In terms of HBV infection and treatment, which of the following is the LEAST LIKELY goal to achieve during therapy? 1. HBV DNA level decrease to less than 5,000 copies/ml 2. HBeAg becomes negative and anti-HBe becomes positive 3. HBsAg becomes negative and anti-HBsAg becomes positive 4. The progression to cirrhosis is delayed DHS/HIV/PP

29. HBV Therapy: Goals Delay/Stop progression of liver cirrhosis Decrease (but not eliminate) risk of HCC Suppress HBV DNA Cause ALT to normalize Shift HBeAg(+) to HBeAg(-) & HBeAb(-) to HBeAb(+) Shift HBsAg(+) to HBsAg(-) & HBsAb(-) to HBsAb(+): Rare Eradicate HBV: Rare DHS/HIV//PP

30. HBV: Loss of Response with NRTIs Resistance to NRTIs DHS/HIV//PP HBV Reverse Transcriptase Mutations From: Nunez M, et al. Lancet ID 2005;5:374-82.

31. HIV/HBV: Screening for HCC A 53-year-old man with HIV and HBV co-infection and has known cirrhosis. CD4 420, VL < 50 copies/ml Taking Tenofovir + Emtricitabine + Ritonavir + Atazanavir Labs show normal ALT/AST levels. HBsAg(+); HBeAg(+); HBV DNA: 1500 IU/ml (baseline 14,000,000). Which of the following is TRUE regarding hepatocellular carcinoma? 1. The patient no longer has risk since his HBV DNA level is < 10,000 copies/ml? 2. His risk is lower since he has cirrhosis 3. His risk is higher because he has HBeAg+ 4. His risk is lower because he is older than 45 DHS/HIV/PP

32. Chronic HBV: Risk Factors for HCC Age > 45 Male gender Detectable HBV DNA HBeAg (+) Presence of cirrhosis Co-infection with HCV DHS/HIV//PP

33. Chronic HBV & Risk of HCC 12 10 8 6 4 2 0 Percent cumulative incidence 012345678910 Year HBsAg+, HBeAg+ HBsAg+, HBeAg- HBsAg-, HBeAg- Yang HI, et al. N Engl J Med. 2002;347:168-74. n=11,893 men, Taiwan

34. Chronic HBV: Screening for HCC 2004 AASLD Guidelines “HBV carriers at high risk for HCC such as men over 45 years, persons with cirrhosis, and persons with a family history of HCC, should be screened periodically with both AFP and US.” “While there are insufficient data to recommend routine screening in low-risk patients with chronic HBV infection, periodic screening for HCC with AFP in carriers from endemic areas should be considered.” DHS/HIV//PP From: Lok AS, McMahon BJ. 2004 AASLD Guidelines

35. Chronic HBV: Screening for HCC 2005 HIV-HBV International Panel “ Screening for this neoplasia (HCC) with ultrasonography and alpha-fetoprotein should be performed in all HBV/HIV cirrhotic patients every 6 months. ” DHS/HIV//PP From: Soriano V et al. AIDS 2005:19:221-40.

36. Antiretroviral Therapy New DHHS Guidelines DHS/PP

37. DHHS Panel: 2004 Antiretroviral Guidelines Initial Therapy: Preferred Regimens Picture Efavirenz + Lamivudine + Zidovudine or Stavudine or Tenofovir Source: www.aidsinfo.nih.gov PI-Based Regimens Lopinavir/Ritonavir (Kaletra) + Lamivudine + Zidovudine or Stavudine NNRTI-Based Regimens DHS/PP

38. Case History: Initiating Antiretroviral Therapy A 34-year-old HIV-infected man presents for follow-up with a CD4 count of 316 cells/mm 3 and an HIV RNA = 72,000 copies/ml. His most recent CD4 count 3 months ago was 323 cells/mm 3. He is motivated to take antiretroviral therapy if you think it would be indicated for him. He has never taken any meds for his HIV disease. Assume the patient is likely to have excellent adherence. Would you recommend starting ARV therapy now? 1. Yes 2. No, but you would have started if HIV RNA > 100,000 copies/ml 3. No, you would wait until CD4 count less than 300 cells/mm 3. 4. No, you would wait until CD4 count less than 200 cells/mm 3. DHS/PP

39. 2005 ARV Guidelines: Recent Major Changes List 5 or more changes in the DHHS guidelines that have occurred in the past 12 months? 1. 2. 3. 4. 5. DHS/PP

40. 2005 ARV Guidelines: Recent Major Changes Major Changes since September 2004: 1. HIV RNA “threshold” changed from 55,000 to 100,000 2. Stavudine move from preferred to alternative 3. Emtricitabine added as a preferred drug in PI- and NNRTI-based regimens 4. Nevirapine NOT recommended (even as alternative) regimen for initial ARV Rx in women with CD4 > 250 and men with CD4 > 400 5. Rifampin can NOT be used safely with ritonavir-boosted PI regimens 6. Tenofovir + Didanosine should NOT be used together for initial Rx 7. Once daily Lopinavir-Ritonavir (6 capsules qd) added for ARV-naïve patients DHS/PP

41. DHHS Panel: 2005 Antiretroviral Guidelines Initial Therapy: Preferred Regimens Picture Efavirenz + Lamivudine or Emtricitabine + Zidovudine or Tenofovir Source: www.aidsinfo.nih.gov PI-Based Regimens Lopinavir-Ritonavir + Lamivudine or Emtricitabine + Zidovudine NNRTI-Based Regimens DHS/PP

42. From: Gathe J et al. 11th CROI:2004: Abstract 570. TDF-FTC + (LPV-RTV qd or LPV-RTV bid) Study 418  Patients (N = 109) - ARV naïv - HIV RNA > 1,000 copies/ml - Randomized trial  Regimens - Backbone: Tenofovir + Emtricitabine - Lopinavir-Ritonavir (800/200 mg qd) - Lopinavir-Ritonavir (400/100 mg bid) Study DesignHIV RNA < 50 copies/ml: 48 Weeks DHS/PP Diarrhea - 16% in qd regimen - 5% in bid regimen

43. Starting Antiretroviral Therapy Acute HIV Infection Year 1 350 200 350 DHS/PP

44. Antiretroviral Therapy Newer Medications DHS/PP

45. Tenofovir plus Emtricitabine (Truvada) Classification: nRTI Dose: 1 pill qd (Tenofovir 300 mg + Emtricitabine 200 mg) Meal Restrictions: none Preliminary 24 week data from Study 934 very promising Adverse Effects: well-tolerated DHS/PP

46. From: Pozniak AL et al. 3rd IAS Path & Treatment. 2005: Abstract WeOa0202. TDF + FTC + EFV versus ZDV + 3TC + EFV Study 934  Patients (N = 509) - ARV naïve, HIV RNA > 10,000 copies/ml - Randomized trial  Regimens - Tenofovir + Emtricitabine + Efavirenz - Zidovudine + Lamivudine + Efavirenz Study DesignResults: 48 Weeks (ITT) DHS/PP

47. Tipranavir (Aptivus) Which of the following is NOT TRUE regarding the use of Tipranavir (Aptivus) in a patient who is highly antiretroviral therapy experienced and has failed several previous regimens? 1. It should always be used with Ritonavir 2. If tolerated, it should be combined with Lopinavir-Ritonavir 3. Response rates are significantly better if used with Enfuvirtide 4. Tipranavir has been associated with cases of severe liver toxicity DHS/PP

48. Tipranavir-r versus LPV-r in PI-Experienced Patients  Background - Tipranavir is novel nonpeptidic PI - Patients failing PI-containing HAART - HIV RNA > 1,000 copies/ml - > 2 PI mutations  Regimens - Optimized background regimen - With/without Enfuvirtide - Randomized to CPI-r* versus Tip-r** Study DesignHIV RNA Reduction > 1 log 10 From: Cooper D, et al. 12th CROI. 2005: Abstract 560. *Most chose LPV-r: subset analysis of LPV-r **Tipranavir 500 mg bid + Ritonavir 200 mg bid

49. DHS/ARV Rx/PP Response to Tipranavir-Ritonavir in Advanced Salvage 50 Tipranavir-Ritonavir + OBR Tipranavir-Ritonavir + OBR + Enfuvirtide

50. DHS/PP Pharmacokinetics of Tipranavir Combined with other PIs  Background - N = 173 - Patients failing PI-containing HAART - HIV RNA > 1,000 copies/ml - > 3 PI mutations (33, 82, 84, 90)  Regimens (OBR in All Arms) - TPR/RTV/Control (500/200) bid - TPR/AMP/RTV (500/600/200) bid - TPR/SQV/RTV (500/1000/200) bid - TPR/LPV/RTV (500/400/100) bid Study Design Tipranavir-r Effect on PIs From: Walmsley S, et al. 15th International AIDS Conference, 2004: Abstract WeOrB1236.

51. Strategic Use of Enfuvirtide/T-20 (Fuzeon) Early Virologic Failure - Likely to be very effective with other new medications Late Virologic Failure - Highly likely to fail if used as the only new effective drug added to failing regimen Recommendation - Defer until you have at least two effective agents available DHS/PP

52. DHS/HIV/ARV Rx/PP Antiretroviral Therapy Future Medications

53. From: Murphy RL, et al. 11th CROI. 2004. Abstract 137. DHS/ ARV Rx /PP D-d4FC (Reverset) ARV-Naïve: Monotherapy Dose-Ranging Study  Background - D-d4C is novel cytidine analog NRTI - Active against NRTI-resistant isolates  Patients (N = 30) - ARV naive - CD4 count > 50 cells/mm 3 - HIV RNA > 5,000 copies/ml  Regimens - D-d4FC: 50 mg qd - D-d4FC: 100 mg qd - D-d4FC: 200 mg qd - Placebo: qd Study DesignResults: Day 10 Data Serious Adverse Events: None

54. From: Cohen C, et al. 3rd IAS Path & Treatment. 2005: Abstract WeOaLB103. DHS/ ARV Rx /PP D-d4FC (Reverset) ARV-Experienced: Monotherapy Dose-Ranging Study  Background - D-d4C is novel cytidine analog NRTI - Active against NRTI-resistant isolates  Patients (N = 199) - ARV experienced (failing) - HIV RNA > 2,000 copies/ml  Regimens - D-d4FC: 50 mg qd - D-d4FC: 100 mg qd - D-d4FC: 200 mg qd - Placebo: qd Study DesignResults: Day 14 Data

55. DHS/PP TMC114/r in Late Salvage Therapy  Background - TMC114 is novel PI - N = 497 enrolled - Heavily 3-class experienced - Multiple PI resistance mutations  Regimens - Background regimen optimized - Enfuvirtide use similar in all groups - TMC-114 plus Ritonavir (dose-ranging) - CPI = Control Protease Inhibitor Study Design 24 Week ITT Data From: Katlama C, et al. 12th CROI. 2005:Abstract 164LB. Subgroup Analysis of TMC-114/r600/100 mg bid - Enfuvirtide Used (naïve): HIV RNA < 50 in 67% - Enfuvirtide not Used: HIV RNA < 50 in 37% *ITT (Missing = Failure)

56. DHS/HIV/PP From: Levy J. N Engl J Med 1996;335:1528-30. HIV Cell Binding and Entry

57. DHS/HIV/PP From: Levy J. N Engl J Med 1996;335:1528-30. HIV Cell Binding and Entry

58. CD4 Cell HIV Inhibitors of HIV Cell Binding and Entry CCR5 CXCR4 CD4 DHS/PP Fusion Domain Vicriviroc (SCH 417690) Maraviroc (UK427,857) GW873140 PRO 140 Enfuvirtide (T-20) AMD-070 PRO 542 BMS-806 TNX355 Fusion Domain gp120

59. DHS/PP Maraviroc (UK-427,857): CCR5 Receptor Antagonist  Novel entry inhibitor (CCR5 Inhibitor)  Provides 1.5 log decrease as monotherapy  Dosing with food decreases absorption  Other CCR5 blockers retain activity against Maraviroc-resistant virus  Good safety profile  Optimal dose unknown

60. DHS/PP Maraviroc: Summary of Studies Performed  Background - Review of 6 studies - All with multiple dose Maraviroc - N = 195 (66 of whom HIV-infected)  Regimens - Maraviroc (dose ranging)  Toxicity - No major toxicity < 300 mg bid Study Design10 day Data: HIV RNA Change From: McHale M. 3rd IAS Path & Treatment. 2005: Abstract TuOa20.04. * Capravirine levels boosted 2-fold by NFV

61. Vicriviroc (SCH 417690): CCR5 Receptor Antagonist From: Schumann D, et al. CROI 2004:140LB. HIV-Infected Volunteers: N =48 HIV RNA Change from Baseline (log 10 copies/ml) CD4 count > 200 cells/mm 3 No ARV Rx for > 8 weeks

62. DHS/ARV Rx/PP HIV Infection: Natural History AIDS Year 1 R5 HIV R4 HIVR5 HIV

63. CD4 Cell R5 HIV HIV Cell Binding and Entry CCR5 CXCR4 CD4 DHS/PP

64. CD4 Cell R5 HIV HIV Cell Binding and Entry CCR5 CXCR4 CD4 DHS/PP

65. CD4 Cell R5 HIV CCR5 CXCR4 CD4 DHS/PP R4 HIV HIV Cell Binding Potential Shift from R5 HIV to R4 HIV

66. CD4 Cell R5 HIV HIV Cell Binding Potential Shift from R5 HIV to R4 HIV CCR5 CXCR4 CD4 DHS/PP R4 HIV

67. CD4 Cell R4 HIV HIV Cell Binding and Entry CCR5 CXCR4 CD4 DHS/PP