Analisis of efficacy and tolerability of raltegravir based regimens by background therapy in salvage: a Mulcicentre Italian Experience.

Background: Despite the official guidelines suggest keeping NRTIs as a component of HAART, evolving concepts in salvage often move the clinicians to limit rescue regimens to active drugs as reported by genotypic tests. Objective: The aim of this analysis is to assess whether simpler rescue regimens are less effective on virus replication control and whether there are differences in toxicity using more or less complex associations. Methods: Patients from the MK0518 EAP were followed-up prospectively since enrolment in the study. Clinical and laboratory data were collected every 2 – 4 months after commercialization. The cohort has been divided for the current analysis in three subgroups: dual regimens (A), triple/quadruple regimens (B) and megaHAART (>4drugs, C). Statistical analysis has been performed using parametric and non-parametric tests. Results: Most of the cohort patients were on triple/quadruple regimens (186/253, 74%). Group A (n=38), B (n=186) and C (n=29) were homogeneous by baseline HIV-RNA (p =0.29), and GSS (p=0.22), while baseline CD4 levels showed a significant trend towards higher CD4 counts in simpler regimens (means: A=351; B=281 and C=164/mmc, p= 0.0009, Kruskall-Wallis test), reflecting a tendency in prescription. No statistically significant differences emerged in the rate of virologic failures or overall treatment discontinuations, and failure was not correlated with lower GSS scores, rather suggesting problems of compliance. Viral failure indeed was more frequent in more complex regimens (A= 5%, B= 11%, and C= 17%). All patients had impressive CD4 gains (A=+242; B=+232; C=+248, p=0,52, paired t test). From a metabolic point of view, no difference was shown for ALT/AST levels, nor for triglycerides, while total cholesterol levels showed a trend to increase over time with more complex drug combinations . Patients on simpler regimens had significantly higher baseline cholesterol. Seven patients died in group B, 4 of non-Hodgkin’s lymphoma (NHL), 1 of acute myocardial infarction, 1 of end stage liver disease and 1 post-transplantation for HCV-related cirrhosis, one died in group C of hepatocellular carcinoma, and no one died in group A . Conclusions: Simpler regimens neither were associated in our analysis with a higher risk of viral failure nor to an impaired CD4+ T cell increase. The metabolic impact of simpler regimens was not related to an important gain in the toxicity profile, except for a slightly reduced increase in cholesterol levels. This analysis will be repeated at 96 weeks to assess long-term tolerability.