HIV/AIDS: Controversies

Transcription

1 HIV/AIDS: Controversies Prevention 2. Treatment Josep M Gatell Hospital Clinic. Barcelona. gatell0@attglobal.net

2 AIDS: year AIDS is a STD and a world wide epidemy (sub-saharan Africa, Southeast Asia, Eastern Europe, America). Is threatening global economical & demographical development and security

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4 AIDS: year Life also is a sexually transmited disease with 100% mortality

5 Adults and children estimated to be living with HIV, 2006 North America 1.4 million [ million] Caribbean [ ] Latin America 1.7 million [ million] Western & Central Europe [ ] North Africa & Middle East [ ] Sub-Saharan Africa 24.7 million [ million] Eastern Europe & Central Asia 1.7 million [ million] East Asia [ million] South & South-East Asia 7.8 million [ million] Oceania [ ] Total: 39.5 ( ) million New: 4 million x Deaths: 3 million Source: 2006 AIDS epidemic update : December 2006 (UNAIDS/WHO, November 2006)

6 New and active patients Hospital Clinic, Barcelona, 2006 current new Telemedicine? Primary care? Number of patients >1/3 foreingers Year and semester

7 100 Factor risk HMS HMF % 40 HET 20 ADI Year

8 Getting older with HIV ACTIVE PATIENTS. H. CLINIC. BARCELONA >50 yr. < 50 yr. PERCENTAGE YEAR

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12 Controversies Prevention 2. Treatment

13 Controversies Prevention Less-traditional prevention methods More HIV testing? Vaginal microbicides?? Diaphragm?? Circumsicion: yes but. PrEP? & PEP Massive treatment?? Partially effective preventive vaccine?

14 Future controversies Prevention 2. Treatment

15 Controversies Treatment: initial Earlier ART (> ) to avoid: non-aids events (cardiovascular) TB, leishmaniasis Hep C & B progression, lymphomas, non-aids malignancies pneumonias hiv nephropaty

16 Incidence of TB in HIV-infected Patients in Barcelona (Spain) x 10 5 per year HIV-infected patients General population - Barcelona - USA, Western EC - South East Asia 1, * Spanish AIDS registry,, 2003

17 Annual incidence of mortality in the HIV-infected cohort compared with general population aged years in Catalonia 5 Mortality per 100 person-years General population HIV-infected cohort Significant reduction in mortality for HIV-infected patients over this period (P<0.001; χ 2 test for trend), but not for the general population (P<0.936; χ 2 test for trend) Martinez et al. HIV Medicine 2007

18 Pacientes activos y tratados nº of patients year active treated

19 Controversies; Treatment: initial Role of new formulations / drugs Atripla: Psychology Maraviroc: Natural niche Raltegravir: Sexy drug TMC 278: CNS, Pregnancy Revisiting eradication Price!!!!!: 50% pharmacy budget

20 Major driving forces Efficacy Tolerance Price Eradication < 1997 < < < >= 2008 < <???

21 Cost Clinic Ruti Bellvitge Total*? 2006 pat.-year#? * Millions of euros; # thousands of euros

22 Distribución porcentual de las pautas de tratamiento de debut en cada año % anual de pacientes que recibe una pauta determinada de debut (sobre el total de pacientes que empiezan su primer tratamiento en cada año) % fármaco 2fármacos nrti nrti+nnrti+ip nrti+1ip nrti+2ip nrti+nnrti otros

23 Protocol 004: Percent (95% CI) of Patients with HIV RNA < 50 copies/ml (NC=F) Percent of Patients with HIV RNA <50 copies/ml * * Week MK mg MK mg MK mg MK mg Efavirenz * P < for MK-0518 at each dose vs. EFV IAC 2006 Abs# THLB0214

24 Hospital Clinic. Barcelona no. % Initial therapy Follow-up 2815 No data 57 < 200 copies copies > copies Total

25 HAART Hospital Clínic de Barcelona Universitat de Barcelona Consejo Superior de Investigaciones Científicas Generalitat de Catalunya No therapy VL Years

26 Controversies: Treatment (simplification; induction / maintenance) improve lipids, lipodystrophy get rid of ritonavir avoid minor side effects class sparing regimens monotherapy with PI/r

27 100% 80% Point prevalence of discontinuations and virologic response OK Triple Discontinued 60% On study, HIV RNA >500 40% On study, HIV RNA % 0% Week On study, HIV RNA < Week Arribas JR. et al., XVI IAC, Toronto, 2006, # THLB0203 OK04

28 Controversies Treatment: salvage < 50 copies for all

29 SALVAGE ANTIRETROVIRAL THERAPY VL ART blib failure salvage ART Dangerous situation 50 90% %

30 Compelling data vs current and future competitors Control Active drug HIV RNA <50 Copies/mL at week Patients (%) % 18% 10% 23% 10% 45% 16% 47% 9% 46% 0 TORO 1 & 2 Enfuvirtide 1 RESIST 1 & 2 Tipranavir/r 2 POWER 1 & 2 Darunavir/r 3 MOTIVATE 1 Maraviroc 4 (150 mg bid) Protocol 005 (Phase II) Raltegravir 5 (400 mg bid) 1. Nelson M, et al, JAIDS 2005;40: ; 2. Hicks CB, et al. Lancet 2006;368: ; 3. Clotet B, et al. Lancet 2007;369: ; 4. Lalezari J, et al. 47 th ICAAC. Abstract H-718a; 5. Grinsztejn B, et al. 47th ICAAC. Abstract H-713

31 Abstract # 105 a&b LB Combined Efficacy* (1) % Patients with HIV RNA < 400 copies/ml at Week 16 by Selected ARTs in OBT Subgroup n % of Patients Overall Efficacy Data Efficacy by ARTs in OBT Enfuvirtide Darunavir : First Use in OBT - : No Use in OBT * Virological failures carried forward Raltegravir + OBT Placebo + OBT

32 SALVAGE ANTIRETROVIRAL THERAPY 5. Failures to >=2 ART regimens PI Entry inh. Integrase inh. NNRTI Lopinavir /r? T20??? Tipranavir/r?? Darunavir /r Maraviroc Raltegravir Etravirine

33 Controversies Treatment: efficacy / toxicity genetic / biological screening? MRP2&4 TDF CYP2B6 EFA, NEV HLA hypersensitivity ABA, NEV UGT bilirrubin ATA Hyperlipidemia, lipodystrophy CCR5 tropism

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36 Controversies Treatment (resource poor settings) reasonable good results scale-up 2nd line therapies (TNF, FTC, Aluvia) how to monitor response

37 Future controversies Prevention Clasical plus non-clasical methods (circumcision) 2. Treatment Role of new drugs in naive patients? Most patients are virologically suppressed. Role of simplification? Goal of salvage therapy is < 50 copies/ml 3. General medical care in old patients 4. Supportive measures: mental health, nutrition

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