Boosted Lopinavir/Ritonavir plus Saquinavir without Additional Anti-HIV Therapy

Presented at the Toronto AIDS conference last week, the LOPSAQ study offers data on the virological, immunological and clinical responses to the boosted double PI regimen combination of lopinavir/ritonavir (LPV/r) 400/100 mg BID and saquinavir (SQV) 1000 mg BID without reverse transcriptase inhibitors (RTI) over 48 weeks in HIV-positive patients who have few viable RTI treatment options.

LOPSAQ is a cohort study of 128 heavily pre-treated patients who were experiencing therapy failure on their current regimen due to resistance or systemic toxicities. Patients were switched to LPV/r + SQV only.

Patients with PI resistance mutations or RTI-toxicity underwent a structured treatment interruption (STI) (n=76) until virus reverted to genotypic susceptibility or until resolution of toxicity symptoms before starting LPV/r+SQV. Response was defined as viral load <400 copies/ml at week 48.

Results

78 (61%) patients experienced a virologic response to therapy.

Median viral load at baseline was 116000 copies/ml; at week 48 median was 144 copies/ml.

Median CD4 at baseline was 172 cells/mm3 compared to 280 cells/mm3 at wk48.

78/128 patients remained on therapy at week 48.

Significant predictors of virologic response included higher CD4 count (p<0.001), lower viral load (p=0.002), less PI-experience (p=0.006) at baseline and fewer PI resistance mutations (p=0.043) at end of prior failing regimen;

In the multivariable analysis only lower CD4 count at baseline (p=0.009) and the greater number of drugs previously taken (p=0.003) could be specified as independent predictors for non-response.

Whereas the STI did not have a significant effect on therapy outcome, it brought a notable benefit in terms of virologic response for a subgroup of patients with extensive PI mutations (>4) at the end of prior failing regimen.

In conclusion, the authors write, "The combination of LPV/r and SQV without RTIs is a potential option as salvage therapy for patients experiencing therapy failure due to resistance or RTI-toxicity."

"This regimen may not be suitable for patients with very low baseline CD4 cell counts, very broad antiretroviral therapy experience or extensive PI-resistance mutations."

08/25/06

Reference
S Staszewski, E Babacan, C Stephan C, and others. The LOPSAQ study: 48-week analysis of a boosted double protease inhibitor regimen containing lopinavir/ritonavir plus saquinavir without additional antiretroviral therapy. 16th International AIDS Conference. August 13-18, 2006. Toronto, Canada. Abstract TUPE0135.