Lopinavir/r exhibits sustained virologic response in antiretroviral-naïve patients: 3-year data

As part of a HAART regimen, lopinavir/r (Kaletra) appears to be a potent, effective and well-tolerated boosted-protease inhibitor combination (lopinavir/ritonavir). One of the initial studies evaluating Kaletra enrolled 100 antiretroviral-naïve, HIV-infected patients with a viral load >5,000 copies/mL and without any CD4 cell count restriction.

In this three-year prospective, randomised study of lopinavir/r, patients were randomised to receive one of three lopinavir/ritonavir doses, all of which were given twice daily (200/100mg; 400/100m; or 400/200mg) together with d4T and 3TC (both given twice daily) after either 3 weeks of lopinavir/r monotherapy (Group I) or from study entry (Group II). After 48 weeks, all patients were converted to open-label lopinavir/r (400/100 mg twice daily).

At week 156, 75% of patients had a viral load <400 copies/mL based on intent-to-treat, noncompleter=failure (ITT NC=F) analysis and 76% had viral loads <50 copies/mL at week 144 (ITT NC=F). Overall, at week 156, the mean CD4 cell count increased 356 cells/mm3, regardless of baseline CD4 cell count.

Fifteen patients experienced loss of virologic response (two consecutive viral load >400 copies/mL following any value <400 copies/mL or failure to achieve <400 copies/mL) through week 156 of which eight demonstrated resuppression either at week 156 or latest available visit without any change in therapy.

Genotyping and phenotyping data was available for six of the seven patients who never regained a virologic response: 0 of 6 had resistance in protease, and three of six had resistance to lamivudine (M184V/I mutation). Twenty-three patients discontinued therapy prior to week 156, five of which were due to reasons possibly related to study drugs (including one death 10 days post thoracic spinal surgery with perioperative MI).

At study entry, 36% of the enrolled patients had a CD4+ cell count <200 cells/mm3, but due to the significant CD4+ T cell count increases only 5% were still <200 cells/mm3 at week 156; similarly, while 56% had a baseline CD4+ cell count <350 cells/mm3, only 14% were still below that level at week 156. Of the five patients with CD4+ <200 cells/mm3 at week 156, two prematurely discontinued during the first 52 weeks due to noncompliance and the other three were on therapy for 144 to 156 weeks with baseline counts of 2-11 clls/mm3 and final counts of 159-192 cells/mm3.

The authors conclude that lopinavir/r, in addition to being safe and well tolerated, exhibits sustained virologic response in long-term follow-up in antiretroviral naïve patients with a significant and sustained increase in CD4+ cell count through 156 weeks regardless of baseline CD4+ cell count.

A Landy, S Brun, M King et al. Three-year immunologic responses in antiretroviral-naïve HIV+ patients treated with lopinavir/ritonavir (Kaletra) based therapy. XIV International AIDS Conference, Barcelona, 7-12 July. Abstract TuPeB4439.