Background: Kaletra® (lopinavir/ritonavir, LPV/r), currently being marketed in France, was prescribed in a pre-registrational expanded access program (ATU) until April 2001. This cohort included 3819 extensively therapy-experienced, moderately immunosuppressed patients. It was able to collect complete baseline informations on clinical and therapeutic histories, as well as numerous patterns of mutations to HIV protease and RT. Prior to entering the program, the patients had been treated with a median number of 3 PIs, 5 NRTIs, 1 NNRTI. 83% subjects were treated at the registered dosage of 3 capsules b.i.d..
Objectives: in 700 patients who had available initial HIV RNA viral load and genotype data, to study the HIV RNA and CD4 responses to Kaletra® and find the correlates with disease status, treatment history, baseline mutational patterns.
Results: at baseline, 57% patients presented with > 6 PI mutations, 68% with > 4 NRTI mutations, 55% had at least 1 major NNRTI mutation. Kaletra® was part of a triple regimen in 56% cases, quadruple in 33%. A virological response (VL< 400 c/mL or > 1 log decrease of HIV RNA) was obtained in 72% patients through 1 month, 68% through 2 months, 65% through 3 months. CD4 increase from baseline was +61, +69, and +89 at the same time-points. Higher rate of initial viral response was correlated with lower initial viral load. The response rate was also highly correlated with the number of PI mutations present at baseline, with for example through 2-3 months : 75% (0 to 5 mutations); 44% (6 to 9 mutations). Correlation was also
found with the number of PIs used in previous regimen : 1-2 PIs : 83% response through 2-3 months, 3-4 PIs : 71%, 5 PIs : 56% . Complete and detailed set of these data will be presented.
Conclusions: In heavily treatment-experienced patients, Kaletra® can achieve a relevant virological and immunological effect, even when up to 5 PI mutations are present. However, subjects with multiple PI experience seem to have a poorer response.
|
