Cristina Mussini Iniziare con CD4>500 cell: vantaggi e svantaggi

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1 Cristina Mussini Iniziare con CD4>500 cell: vantaggi e svantaggi
Lunedì 8 marzo II SESSIONE Quando iniziare Raccomandazioni internazionali a confronto sul management terapeutico del paziente HIV Expert opinion Iniziare con CD4>500 cell: vantaggi e svantaggi Cristina Mussini Clinica di Malattie Infettive, Azienda Ospedaliera Universitaria, Policlinico di Modena 1

2 In un mondo ideale

3 L’approccio terapeutico all’infezione da HIV non dovrebbe differire da quello usato nei confronti delle altre infezioni e cioè la terapia dovrebbe essere iniziata immediatamente dopo la diagnosi.

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5 Risk of death associated with deferral of ART, according to CD4+ count at baseline, with adjustment for HIV-RNA level, age, and sex Kitahata MM, et al. N Engl J Med, 2009

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7 Hazard ratios for AIDS or death for deferral of cART to a lower CD4 cell count range versus initiation at a higher CD4 cell count range When To Start Consortium, Lancet, 2009

8 -24 -24 -18 -18 -12 -12 -6 -6 -24 -18 -12 -6 -24 -18 -12 -6 -24 -18 -12 -6 -24 -18 -12 -6 months (A) (B) (C) n = 411 median: +20 range: (-4; + 883) n = 403 median: - 182 range: (-626; -124) n = 800 median:- 56 range: (-125; -5) Legend figure 2: Box-plots showing CD4 24 months before HAART according to 3 different pre-HAART CD4 patterns (A, B and C: steeper, in-between and constant, respectively).

9 Legend fig 3: graphs representing pre- and post-HAART CD4 slopes
Group A (steepest pre-HAART CD4 rate) pre-HAART CD4 slope: cells/mm3 /month (95% CI: from to -8.9) post-HAART CD4 slope: cells/month (95% CI: from to 26.9) Group B (moderate pre-HAART CD4 rate ) pre-HAART CD4 slope: cells//mm3 month (95% CI: from -4.6 to -3.1) post-HAART CD4 slope: cells/month (95%CI: from to 16.2) Group C (shallowest pre-HAART CD4 rate) pre-HAART CD4 slope: cells//mm3 month (95% CI: from to +2.2) post-HAART CD4 slope: cells/ month (95% CI: from +7.1 to +15.1) Legend fig 3: graphs representing pre- and post-HAART CD4 slopes estimated by linear mixed models for the three groups (A, B and C)

10 Duration of first STI period according to CD4 nadir
Off therapy (days) Mean %CI

11 CD4 naïve/memory cell ratios in patients with incomplete immunological response
STRATUM 1: CD4 nadir 50 cell/L STRATUM 2: CD4 nadir 50 – 200 cell/L Robbins et al. CID 2009

12 T Cell Activation Declines Further During ART-mediated VL Suppression
Hunt et al, JID, 2003 and 2008

13 La vita reale

14 CD4 counts are low at start of HAART
2003–2005 42 countries 176 sites 33,008 patients Although HAART is introduced in Europe at a CD4 cell count of approximately 200 cells/mm3, it is introduced at substantially lower counts in most other parts of the World. In several countries in Africa, therapy is initiated at counts <100 cells/mm3 This may partly be a reflection of poor resources. However, even in the USA and Canada, therapy is introduced at counts <200 cells/mm3 (the level below which guidelines recommend initiation even if patients are asymptomatic).1−3 In addition to resource constraints, poor awareness of guidelines and concern about adverse effects of HAART may discourage earlier initiation of HAART. References 1. EACS guidelines for the treatment and management of HIV-infected adults and adolescents in Europe, 2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. November 3, 2008; Available at 3. Hammer S, et al. JAMA 2008;296:555–570 Adapted from Egger M, 14th CROI Los Angeles, CA, USA, 25–28 Feb Abstract 62. ART Cohort Collaboration.

15 Conclusions Regimens containing TDF/FTC or ABC/3TC increased limb fat and trunk fat and were not significantly different ATV/r led to greater gain in limb fat and trunk fat than EFV Lipoatrophy, even the mild protocol-defined form, occurred in 16% (95% CI %) of the participants and was not significantly different between TDF/FTC and ABC/3TC or between EFV and ATV/r A5224s 15

16 Cumulative ARV Exposure and Risk of Chronic Kidney Disease in EuroSIDA
s6843 HIV-infected patients with ≥ 3 serum creatinine measures and corresponding body weight measures from EuroSIDA study 21,482 patient-yrs of follow-up Cumulative exposure to TDF, ATV, LPV/RTV, or IDV each associated with increased risk of chronic kidney disease Risk of chronic kidney disease after stopping TDF remained elevated for 1 yr Within 12 mos, IRR: 4.05 ( ) After 12 mos, IRR: 1.12 ( ) Risk of chronic kidney disease after stopping ATV or LPV/RTV similar to patients never exposed Kirk O, et al. CROI Abstract 107LB.

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21 Corsi e ricorsi storici
Giambattista Vico (1668–1744) Corsi e ricorsi storici

22 Antiretroviral Therapy for HIV Infection in 1996: Recommendations of an International Panel Charles C. J. Carpenter; Margaret A. Fischl; Scott M. Hammer; Martin S. Hirsch; Donna M. Jacobsen; David A. Katzenstein; Julio S. G. Montaner; Douglas D. Richman; Michael S. Saag; Robert T. Schooley; Melanie A. Thompson; Stefano Vella; Patrick G. Yeni; Paul A. Volberding JAMA. 1996;276(2):

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24 Corsi e ricorsi storici
Giambattista Vico (1668–1744) Corsi e ricorsi storici Il senso della storia è, per Vico, sia nella storia che, nello stesso tempo, fuori di essa: gli effetti delle azioni umane vanno sempre oltre l’intenzionalità specifica degli uomini; l’uomo fa più di quanto sa e spesso non sa quello che fa. La storia è caratterizzata, secondo Vico, da un andamento progressivo ma non nel senso che tutto quello che viene dopo sia migliore di quello che viene prima, ma solo nel senso che la storia procede in un modo non meccanico né uniforme verso l’idealità

25 CONCLUSIONI I clinici hanno sempre avuto buon senso nel seguire le linee guida e in questi anni hanno iniziato la terapia antiretrovirale senza seguire gli opposti estremismi. Vi sono ancora molte cose che non sappiamo e per rispondere non basterà uno studio randomizzato ma a breve termine. Certamente abbiamo spostato nella nostra pratica clinica l’inizio della terapia verso i 400 CD4 e non credo che i dati in nostro possesso siano in grado di far spostare il limite più in alto.