Background of study: PI-including HAART regimens though very potent combinations, are often changed due to adverse reactions and/or low adherence. PI-sparing regimens show high potency and are often used as semplification therapy in patients with well controlled viral replication and good immunological response during PI-containing treatment.
Objective: To evaluate in a cohort study the efficacy and toxicity of semplification regimens in patients with well controlled viral replication who switched from PIs to NNRTI or to Abacavir (ABC) containing treatment.
Design Inclusion criteria were:
- HIV-RNA<500 cp/ml and CD4+>200/mmc for at least 6 months during a first PI containing HAART;
- NNRTI and ABC naïve;
- Changing the PI with Efavirenz (EFV) or Nevirapine (NVP) or ABC while maintaining the same NRTIs.
Endpoints of the study were: virological failure (at least one HIV-RNA>500 cp/ml), immunological failure (decrease of CD4+ count of 20% or more from baseline value and CD4+<500/mmc) and discontinuation of at least one drug of the treatment regimen. Data were analysed by intention to treat; multivariate analyses (Cox model) were performed to assess the factors independently related with virological or immunological failure.
Results: Of the 109 patients included in the study, 80 (73,4%) were men; 33 (30,3 %) were IVDU; the median age was 35 years. 20 patients (18,3%) were on CDC stage C, median CD4+ was 562/mmc (range 214-1651 ) and median period of undetectable
HIV-RNA was 611 days (181-1573); median period of PI-HAART was 511 (183- 1480 ). 81 (74%) patients shifted from an Indinavir-, 18 (16,5%) from a Nelfinavir-, 8 (7,3%) from a Ritonavir- and 2 (1,8%) from hg-Saquinavir-containing regimen. 38 (34,8%) patients were given NVP-including regimens, 58 (53,2%) EFV and 13 (12%) ABC. In a median follow-up of 286 days (range 30-720) 29 patients (26,6%) discontinued the PI-sparing regimen because of toxicity (n=21, 19%) or failure (n=8, 7,6%). Patients treated with NVP showed a higher indipendent risk of therapy discontinuation (HR: 3,3; 95% CI: 1,3-8,4; p= 0,01 vs EFV). Virological failure occurred in 32 patients (29,4%). A longer duration of previous HAART was associated to a better virological outcome
(for each day more HR: 0,99; 95% CI: 0,99-10; p= 0,05). Patients given NVP showed an indipendent higher risk of virological failure as compared to EFV-treated ones (HR: 3,0; 95% CI: 1,3-7,0; p=0,01). Immunological failure occurred in 19 patients (17,4%). Indipendent factors predictive of such an end-point was a diagnosis of AIDS at baseline (HR: 4,4; 95% CI: 1,5-12,8; p=0,007).
Conclusions: Our study demonstrates that switching from a PI-including to a PI-sparing regimen, in subjects with well controlled viral replication, has to be carefully valuated. In fact, only cases with a long term control of viral replication on PI-including regimens can obtain mainteinance of virological success. The higher risk of virological failure in patients on NVP
might be also attributable to a higher frequency of therapy discontinuation due to cutaneous adverse events.
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