4 CASCADE: Nadir CD4 count predicts AIDS and non-AIDS events CASCADE collaboration cohort (n = 9858)AIDS-related deathNon-AIDS-related deathNadir CD4+ cell count200–349 vs ≥ 350200–349 vs ≥ 35050–199 vs ≥ 35050–199 vs ≥ 350< 50 vs ≥ 350< 50 vs ≥ 3500.011.00100.000.011.00100.00Liver disease deathNon-AIDS cancer death200–349 vs ≥ 350200–349 vs ≥ 35050–199 vs ≥ 35050–199 vs ≥ 350< 50 vs ≥ 350< 50 vs ≥ 3500.011.00100.000.011.00100.00Marin et al. IAS Abstract WEPEB019
15 Sono queste le strategie che potremmo utilizzare oggi??? ACTG 384DDI/d4T/EFV/NFVAZT/3TC/EFV/NFVACTG 5095AZT/3TC/ABC/EFVma.....Sono queste le strategie che potremmo utilizzare oggi???
16 Considerations for First-line Therapy Pt FactorsAntiretroviral Drug FactorsReadiness/commitmentBaseline drug resistanceBaseline CD4+ cell count/HIV-1 RNATolerabilityAgeLong-term toxicitySexDrug interactionsOccupationDosing frequencyComorbid conditionsPill burdenPlans for pregnancyPharmacokineticsAccess to careCostConcurrent medicationsAdherence to other medicationsThis slide reviews patient‑ and drug-associated factors that might affect choice of first-line regimens. Most clinicians are familiar with these issues, but a patient’s occupation might be important or their ability to tolerate a high pill burden, dose frequency, or pharmacy cost. All of these factors need to be taken into consideration.16
17 Adjusted risk of triple class virologic failure after the start of cART Lodwick R, for COHERE, 16th CROI; Montreal (CA), 2009
18 Boosted-PIs are associated with lower risk of HIV resistance at any level of adherence ***Plasma vira load logLima VD et al, JID 20081818
19 PI Efficacy at Higher and Lower Baseline HIV-1 RNA Systematic review of 21 treatment arms from 12 treatment-naive clinical trials reported from January March 2008 (N = 4895)Conclusion: significantly ↑ rates of HIV-1 RNA < 50 copies/mL at 48 wks with TDF/FTC vs ABC/3TC by ITT-TLOVR or nearest equivalent endpointLPV/RTVTDF (n = 1798)< 100,000 copies/mLABC (n = 787)≥ 100,000 copies/mLATV/RTVTDF (n = 440)ABC (n = 433)FPV/RTV3TC, lamivudine; ABC, abacavir; ATV, atazanavir; DRV, darunavir; FPV, fosamprenavir; FTC, emtricitabine; ITT-TLOVR, intent-to-treat-time to loss of virologic response; LPV, lopinavir; RTV, ritonavir; TDF, tenofovir; VF, virologic failure.On the other hand, the data are not quite the same with boosted PIs. These data are from a presentation by Hill and colleagues at the 2008 joint Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Diseases Society of America meeting. In this graph, individuals who had HIV-1 RNA < 100,000 copies/mL at baseline are represented by dark circles and patients who had HIV-1 RNA ≥ 100,000 copies/mL at baseline are represented by open circles. These are 48‑week data. For each boosted PI pair, regardless of whether patients received tenofovir or abacavir, a higher response rate was seen when HIV-1 RNA was < 100,000 copies/mL than when baseline HIV-1 RNA was ≥ 100,000 copies/mL. The clinical importance of this finding is not entirely clear, and although these are data from randomized studies, these are not randomized comparisons. However, it is helpful to keep in mind that at very high HIV-1 RNA levels, the pace of suppression to HIV-1 RNA < 50 copies/mL seems to be at a lower rate with the boosted PIs.TDF (n = 53)ABC (n = 756)DRV/RTVTDF (n = 343)405060708090100HIV-1 RNA < 50 copies/mL at 48 Wks (%)Hill A, et al. ICAAC/IDSA Abstract 1254.1
20 Emergenza di resistenza e ricombinazione virale CD4Viremia plasmaticaRicombinazione intracellularedel materiale genetico di HIVGiorni di HAART
22 Viral load (RNA copies/ml plasma) Time after ART initiation (months) Patient with detectable minority quasispecies of drug-resistant HIV-1 at baseline and selection of drug-resistant variants during initial months of 1st ARTK103N variant (RNA copies/ml)Viral load (RNA copies/ml plasma)M184V variant (RNA copies/ml)Time after ART initiation (months)
23 Emergenza di resistenza e ricombinazione virale CD4Viremia plasmaticaRicombinazione intracellularedel materiale genetico di HIVGiorni di HAART
24 Decay of viral load with RTG vs. EFV in study P004 36 → 30 patientsRTG150→ 121 patientsMurray, AIDS 200724
25 PROGRESS: Primary Efficacy Endpoint at Week 48: LPV/r + RAL was non-inferior to LPV/r+TDF/FTC in treatment-naïve subjects at 48 weeksPROGRESS 48 week results – XVIII IAC19-Jul-10
26 SPARTAN : Response Rate (HIV RNA < 50 c/mL) through Week 48 VR-OC ATV+RALATV+RTV + TDF/FTC100n82.2%nonnnnoonn80nnnoooo76.0%o60noPercent Responders (95% CI)o40on20ooonB/L4812162024283236404448WeeksATV+RAL: N=ATV+RTV+TDF/FTC: N=VR-OC is an on-treatment method. It classifies subjects as responders according to a single on-treatment HIV RNAmeasurement < 50 c/mL closest to the planned visit and within a pre-defined visit window. The denominator is basedon subjects with an on-treatment HIV RNA measurement in that visit window.IAC July 22, 2010: SPARTAN: THLBB204
27 Mean CD4 change from baseline through week 48 ATV+RALATV+RTV + TDF/FTCon50100150200250300B/L4812162024283236404448235197Mean CD4 Changecells/mm3 (SE)WeeksATV+RAL: N=ATV+RTV+TDF/FTC: N=ATV+RAL: Mean CD4 change from baseline at week 24: 166ATV/RTV + TDF/FTC: Mean CD4 change from baseline at week 24: 127IAC July 22, 2010: SPARTAN: THLBB20427
32 CXCR4-specific viral load predicts disease progression during ART Kaplan–Meier curves of the association of clinical progression with quantity of X4 and R5 (QXR) at baseline of 1 ( ) and < 1 ( )Weiser B, AIDS 2008
33 Caso clinico : consulenza infettivologica in neurologia Uomo 38 anni, ricoverato (1/10/200) presso il reparto di neurologia per rallentamento ideo motorio e disturbi neuro-psichiatrici.Condizioni generali scadute,paziente febbrile (38°C), parametri emodinamici stabili.Tono dell’umore fortemente depresso.
34 AnamnesiA febbraio 2009 riduzione tono dell’umore, apatia con ritiro sociale, ideazioni a carattere paranoideo, insonnia.Marzo 2009 ricovero per “sindrome depressiva severa con idee melanconiche“ in clinica psichiatrica a Monaco. Viene consigliata terapia antipsicotica e antidepressiva.
35 Test HIV ELISA E Western Blot positivo Esame obiettivoRallentamento nei movimenti e nell’eloquio, vigile, non orientato nel tempo e nello spazio, no deficit neurologici sensitivo-motori.CD4+:27 /μL (6%), HIV RNA cp/mlTest HIV ELISA E Western Blot positivo
36 RMN Encefalo….aree di alterata intensità del segnale, iperintense in corrispondenza della sostanza bianca periventricolare delle corona radiata e dei centri semiovali bilateralmente …..….circoscritta area di alterata intensità del segnale in sede fronto basale sinistra …
37 Fibroncoscopia con Broncolavaggio TC Torace…aspetto a vetro smerigliato, più evidente a livello dei lobi superiori in sede mantellareFibroncoscopia con BroncolavaggioPneumocystis jirovecii esame microscopico, ricerca diretta e PCR: positvo