1 / 50

EMERGING ISSUES IN HIV PATIENT CARE

EMERGING ISSUES IN HIV PATIENT CARE. John G. Bartlett Johns Hopkins University School of Medicine Conflicts : HIV Advisory Boards – BMS, Pfizer, Abbott, Tibotec, GSK; Policy Advisory Board – J & J. HIV TREATMENT: WHAT WE HAVE LEARNED IN 20 YEARS. Cannot cure

ronna
Télécharger la présentation

EMERGING ISSUES IN HIV PATIENT CARE

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. EMERGING ISSUES IN HIV PATIENT CARE John G. Bartlett Johns Hopkins University School of Medicine Conflicts: HIV Advisory Boards – BMS, Pfizer, Abbott, Tibotec, GSK; Policy Advisory Board – J & J

  2. HIV TREATMENT: WHAT WE HAVE LEARNED IN 20 YEARS • Cannot cure • Need 2 active drugs and 2 classes (prefer 3) • Goal of therapy is viral suppression to <50 c/mL (This is viral “shut down”) • Virologic failure is due to resistance or non-adherence • Adherence is critical, but not 95% • Failed therapy works • We do not know how to prevent HIV • Last 10 years – simplification, potency and tolerance • Next three years – salvage • The Ryan White Care Act is critical

  3. EMERGING ISSUES IN HIV PATIENT CARE (No order) • ABC – HSR screening • SMART messages – non HIV-related complications • New drugs – where will they fit • Acute HIV – Transmission & natural history • When start – earlier • Prevention – greatest failure • HIV testing – everyone • Resistance – perspective • Progress – unparalleled • HIV care – who will do it and who will pay

  4. GENETIC SCREENING FOR ABC-HYPERSENSITIVITY(Rauch A. CID 2006;43:99) Method: Baseline screen for HLA-B* 5701, 2002-05 Results: ABC Hypersensitivity Prescreen 16/199 (8%) Post screen 3/151 (2%) *3/3 had positive tests

  5. PREVALENCE OF HLA-B* 5701 US white 8% Middle East 1-2% Afro Am 2.5% India 5-20% Hispanic 2% Thailand 4-10% Asian 1% Africa <1% S. America 5-7% China 0 UK 8% Japan 2% Australia 8% W. Europe 7%

  6. INITIAL THERAPY: DHHS GUIDELINES 10/16/06 NNRTI PI NRTI Preferred EFV AZT/r TDF/FTC FPV/r AZT/3TC LPV/r Alternative NVP ATV ABC/3TC FPV ddI/3TC FPV/r qd LPV/r qd

  7. INITIAL THERAPY: DHHS GUIDELINES 10/16/06 NNRTI PI NRTI Preferred EFV AZT/r TDF/FTC FPV/r ABC/3TC LPV/r Alternative NVP ATV AZT/3TC FPV ddI/3TC FPV/r qd LPV/r qd

  8. GILEAD 934: TDF/FTC VS. AZT/3TC(Gallant J. NEJM 2006;354:25) Regimen N <50 ADR TDF/FTC/EFV 255 77%* 4%* AZT/3TC/EFV 254 68% 9% *P<0.05

  9. SMART CD4 guided treatment interruption (NEJM 2006;355:2283) Method: CD4 >350 randomized to • Continuous treatment • Stop until CD4 <250 Results: 5472 pts from 33 countries DC CT RR P Progression/death 120 47 2.6 <0.0001 Complications* 65 39 1.7 0.02 Death 55 30 1.8 0.04 *MI, CVA, by-pass, liver/renal disease Subset analysis (16th IAC WEAB204): No benefit to any group

  10. HIV RISK OF MALIGNANCY: D:A:D (Antonella. 14th CROI 2007; Abst #84) Method: Analysis – 11 cohorts; 23,441 pts CD4 AIDS cancers* Non-AIDS cancers Rate* RR Rate* RR <50 20.1 175 6.0 15 50-99 4.8 41 9.6 19 100-199 2.8 24 6.8 10 200-349 0.7 6 2.0 3 350-499 0.3 3 1.0 2 >500 0.1 1 0.6 1 *Rate/1000 patient-years *Lung – 62, GI – 41, hematologic -- 20

  11. CD4-GUIDED STI: STACCATO(Ananworanich J. Lancet 2006:368:459) Issue: Cost, complications, efficacy STI Method: CD4 threshold 350 Results: 22 mo. STI Continuous n=284 n=146 Baseline CD4 470 506 CD4 count 484 655* VL <50 c/mL 91% 92% Time off HAART 62% 1%* Resistance mut. 2.5% 2.1% *P <0.01

  12. SMART: WHAT IT SHOWED AND DID NOT SHOW Showed: STI (CD4 250/350) risks • HIV progression • Non-HIV-related complications – cardiac, hepatic, cancer • Resistance Did not show: • Risk of CD4 350 threshold to treat • Resistance with PI-based HAART • Cost effectiveness of continuous treatment

  13. ANTIRETROVIRALS IN DEVELOPMENT* NRTI NNRTI PI EI Other Preclinical 12 10 7 21 11 Phase 1 2 1 1 2 --- Phase 2 3 2 --- 4 --- Phase 3 --- --- 1 --- --- *www.aidsinfonyc.org/tag/tx/pipeline

  14. SALVAGE: EVOLVING STRATEGIES 2000-03 2005-06 2006-08 Structured Rx T20 TMC-125 interruption TPV/r TMC-278 Mega HAART DRV CCR5/CX4 Double boosted Integrase PIs inhibitors

  15. SALVAGE (3 CLASS RESISTANCE)48 WEEK DATA No. <50 c/mL at 48 weeks All patients Enfuviritide Study Study OBR Study OBR drug drug RESIST-TPV/r (1) 23% 10% 36% 14% POWER-DRV/r (2) 46% 10% 58% 11% • Lancet 2006;368:466 • Lazzarin -- 16th IAS 2006; Abstract TUAB0104

  16. RILPRIVIRINE (TMC 278) (3 doses)* vs. EFAVIRENZ in 368 TREATMENT-NAÏVE PATIENTS: 48 WEEKS RESULTS(14th CROI. Abst 144LB) RPV EFV n=279* n=89 Baseline CD4 200 207 VL log 10/mL 4.8 4.9 Results – 48 wks VL <50 c/mL 79% 81% CD4 +138 +127 ADR CNS 5-10% 10-30% LDL chol 0 +16 *25, 75 & 150 mg qd; 75 mg/d for future

  17. Maraviroc (UK-427,857) Monotherapy Mean Reduction in Viral Load From Baseline Last day of dosing 0.5 0.0 Maraviroc dose n -0.5 Placebo 015 4 Change from baseline (log10 HIV-1 copies/mL) Placebo 007 12 25 mg QD 8 -1.0 50 mg BID 8 100 mg QD 8 100 mg BID 7 150 mg BID Fast 8 -1.5 150 mg BID Fed 8 300 mg QD 8 300 mg BID 8 -2.0 Baseline 5 10 15 20 25 30 35 40 Time (day) Study 1007/1015 Fätkenheuer G et al.15th IAC 2004; abstract TuPeB4489.

  18. MOTIVATE 1 & 2: Maraviroc/OBR in 1,048 patients with triple class resistance at 24 weeks.(14th CROI; Abst. 104 a & b LB) OBR MVC/OBR Decrease HIV RNA -0.93 -1.96* <50 c/mL 23% 49%* CD4 count increase +58 +106* D/C for ADR 4% 5% *P <0.01

  19. PHASE II TRIAL OF RALTEGRAVIR IN TREATMENT EXPERIENCE PATIENTS(B. Grinsztejn. Lancet 2007;369:1261) Protocol: 3 doses (200, 400, 600 mg bid) vs. placebo in treatment-experience pts with viral failure Enrollment: AIDS-83%, Prior treatment – 9.9 yrs, antivirals – 12; no other active agents – 75%, prior ENF – 30%

  20. BENCHMARK 1 & 2: Raltegravir(MK-0518) in patients with triple class resistance at 16 wks(14th CROI Abst 105 a & b LB) OBR RGV/OBR n=237 n=462 Decrease HIV RNA -1.0 -2.0* HIV RNA <400 c/mL 42% 77%* HIV RNA <50 c/mL 35% 61%* CD4 count increase +36 +85* D/C for ADR 1.7% 2.1% *P<0.01

  21. HIV Incidence in U.S.Over 25 Years of AIDS 180,000 Pre-ARV ARVs, pre-HAART Decade of HAART 160,000 140,000 HIV Incidence 120,000 100,000 80,000 60,000 40,000 20,000 000 1978 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 1979 Year ≥ 40,000 infections annually despite improvements in therapy !

  22. September 22, 2006 CDC Recommendations Routine Testing for HIV-1 • Routine voluntary testing for patients ages 13-64 in health care settings – not based on patient risk • Opt-out testing • No separate consent for HIV • Pre-test counseling not required • Repeat HIV testing left to discretion of provider, based on patient risk

  23. Awareness of Serostatus Among People with HIV and Estimates of Transmission Accounting for: ~ 25%Unaware of Infection ~54%of New Infections ~75%Aware of Infection ~46% of New Infections People Livingwith HIV/AIDS1,039,000-1,185,000 New Sexual Infections Each Year~32,000 Marks G, et al AIDS 2006; 20:1447-1450.

  24. “Missed opportunities . . .”* Review 4,315 cases HIV S. Carolina, 2001-05 Results: 41% HIV first reported within 1 year of AIDS Analysis of 3,054 “late testers” No. healthcare visits with no HIV test: 19,296 (Ave 6/pt.) within 3 years ● Risk based testing visits: 3,888 *MMWR2006;55:1269; 14th CROI; Abst 957

  25. MEAN CD4 COUNT AT TIME HAART IS STARTED(Egger. 14th CROI Abs #62) Method: Analysis of >30,000 patients in cohorts Results: Area CD4 Africa <100/mm3 Western Europe 150-180/mm3 US/Canada 169-187/mm3

  26. AIDS EVENTS AMONG PATIENTS INITIATING HAART(Sabine C. AIDS 2005;19:1995) Method: ART Cohort Collaboration – 12 cohorts, 22,217 patients Analysis of AIDS events at 0-7 mo after starting HAART 1996-2003 CD4 at HAARTEvent rate CD4 at 6 mo <50/mm3 45.1 114/mm3 50-199/mm3 16.9 229/mm3 200-349/mm3 4.5 385/mm3 >350/mm3 2.2 600/mm3

  27. WHEN TO START: >350? • Current experience – late starts everywhere • Limited CD4 recovery • Adherence demands are overstated • Regimens are simplified, potent and less toxic • Early Rx supported by large trials • Resistance – stabilized, more classes, PI data • Prevent transmission • Non-AIDS –related complications – ca etc

  28. ADHERENCE NNRTI-BASED HAART AND VIRAL OUTCOME (Nachego J. Ann Int Med 2007;146:564) Methods: Adherence based on pharmacy claims (Total/#months) for 2,764 pts correlated with sustained VL <400 c/mL for 2.2 yrs Results: (200-997 pts/10 percentile) <50%: 13% 70-79%: 45% 50-59%: 25% 80-89%: 59% 60-69%: 39% >90%: 72%

  29. HIV TRANSMISSION DYNAMICS(Brenner B. JID 2007;195:951) Method: Sequence analysis pol to detect clusters Quebec cohort 1998-2005. Cluster defined as <2% variation Results: Number analysis = 593 patients Transmission clusters = 75 Co-segregation = 293 (49%) Average cluster = 4 (2-17) Conclusion: Early infection accounts for half of transmissions

  30. TRANSMITTED DRUG RESISTANCE(Wensing A. 16th IAC, TUAB0101) Method: European Commission supported study of baseline ART resistance Results: 2002-03, 1083 pts subtype B-66%, A-9%, C-9% Resistance 96/1083 (9.1%) ● NRTI 5.4% (215, 41, 219) ● PI 3.0% (46, 90, 82) ● NNRTI 2.6% (103, 108) Risk: seroconverters and type B

  31. BASELINE RESISTANCE: US, 2003-06 – 3,130 PATIENTS(Wheeler. 14th CROI; Abst 648) NRTI NNRTI PI Total 111 (3.6%) 217 (6.9) 75(2.4%) Mutations 41L-45% 103N-70% 90M-40% 67N-24% 108I-12% 46I-19% 184V-23% 181C-11% 46L-19% 219Q-17% 190A-9% 30N-8%

  32. ACTG 5142: EFV vs. LPV/r(Riddler SA. 16th IAC THLP0204) Results: 96 wks EFV LPV/r EFV/LPV/r n=253 n=253 n=250 VL <50 c/mL 89%* 77% 83% CD4 count +241 +285* +268 Resistance 48%* 4% 68% Gr 3-4 ADR 18% 19% 20% *P= <0.05

  33. ACTG 5142: RESISTANCE AT VIROLOGIC FAILURE LPV/r EFV + LPV/r +2NRTIs 2NRTIs EFV No. failures 94 60 73 Genotype assay 52 33 39 Mutations RT 184V 7 8 1 103N 0 9 21 PI 0 0 2 2 classes 2 10 2

  34. NO RESISTANCE AFTER PI FAILURE Trial* PI Resistance STACCATO (1) SQV/r 0/10 SOLO (2) FPV/r 0/32 M 98-863 (3) LPV/r 0/51 • WePe 4.4C12 • AIDS 2004;18:651; • JID 2004;189:51

  35. Survival Benefits for Each Era

  36. WHO HAS HIV/AIDS? Race: Insurance ● Black: 53% ● Uninsured: 28% ● Hispanic: 10% ● Medicaid: 34% ● White: 37% ● Medicare: 13% ● Private: 16% Income ● <$10K/yr: 45% ● Unemployed: 62%

  37. MEAN EXPENSE/PATIENT/YEAR FOR 635 PATIENTS AT UAB HIV CLINIC(Chen RY. CID 2006;42:1003) Category Total (%) ART Agents $10,500 (56%) Meds (other) $ 4,240 (23%) Hospital cost $ 2,342 (13%) OPD, lab, x-ray $ 1,199 (6%) Physicians/clinic $ 359 (2%) Total $ 18,640 (100%)

  38. EMERGING ISSUES ABC HST: First routine genetic test SMART: 1) Never stop (? Staccato) 2) Non-HIV-related complications New drugs: 1) Class 5 – CCR5, 2) Class 6 – Integrase Inhibitor (2007) Prevention: 1) Global failure, 2) US: Increase PLWA 25,000/yr When start: 10 reasons to start >350

  39. EMERGING ISSUES HIV serology: Test everyone to -- 1) Improve prevention 2) Early ART Acute HIV: 1) Is it all over in 3 weeks? 2) Prevention opportunity Resistance: 1) Not increasing 2) Pipeline rich Progress: 1) Unmatched 2) Velocity of new data, standards, practice Resources: 1) Who will pay? 2) Manpower concerns

  40. The End

More Related