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.
|
