Lopinavir/r effective in naive patients after three years of treatment

As most clinicians are aware, lopinavir/r is a co-formulation of lopinavir (LPV) and ritonavir (r), with the ritonavir functioning to increase lopinavir levels by acting as an inhibitor of cytochrome P450 3A.

At a dosage of 400 mg of LPV/100 mg ritonavir twice daily, ritonavir concentrations are below those required for antiviral activity whilst the mean LPV Ctrough/IC50 ratio for wild-type HIV is high, potentially providing a barrier to the emergence of vial resistance and activity against resistant virus.

The M97-720 study is an ongoing phase II double-blind trial of LPV/r in combination with d4T and 3TC in antiretroviral-naïve patients. The three-year follow-up data on safety and efficacy through 156 weeks was presented as a poster at the 8th ECCATH.

One hundred antiretroviral-naïve patients were randomised to receive one of three dosage levels of LPV/r (200/100 mg BID, 400/100 mg BID or 400/200 mg BID) plus d4T (40 mg BID) and 3TC (150 mg BID) given after 3 weeks of monotherapy (Group I) or from day 1 of the study (Group II). After 48 weeks, all patients began conversion to open-label LPV/r 400/100 mg BID dosing.

Using an intent to treat, non completer equals failure, analysis, the authors found that 75% of patients achieved an HIV RNA <400 copies/mL at week 156 and that 76% achieved an HIV RNA <50 copies/mL at week 144. Also, the proportion of patients maintaining virologic response through week 156 was 84.1% using Kaplan-Meier estimate and the mean CD4+ T cell count increased from 298 cells/mm3 to 654 cells/mm3 through week 156.

The authors conclude, “LPV/r based therapy exhibits sustained virologic response over long-term follow-up in antiretroviral-naïve patients [and] among subjects for whom ARV therapy would be recommended by current treatment guidelines, virologic and immunologic response appear comparable to overall results from the study.” Finally, “LPV/r was well tolerated, as indicated by the low rate of study discontinuations due to LPV/r-related adverse events (5/100, 5%).”

M Thompson and others. Kaletra (lopinavir/ritonavir) in Antiretroviral-naïve HIV+ Patients: 3-Year Follow-up. 8th European Conference on Clinical Aspects and Treatment of HIV Infection (October 27-31, 2001, Athens Greece). Abstract 225.