A combination antiretroviral regimen consisting of lopinavir/ritonavir (Kaletra) plus the integrase inhibitor raltegravir (Isentress) without nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) works as well as a traditional three-drug cocktail, according to findings from the PROGRESS study presented this week at the Eighteenth International AIDS Conference in Vienna.
Highly active antiretroviral therapy, or HAART, traditionally includes a protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI), plus a 'backbone' of two NRTIs. But nucleoside/nucleotide drugs can cause long-term toxicities, and development of new classes of HIV entry and integrase inhibitors has allowed more flexibility in constructing potent regimens.
Jacques Reynes and fellow investigators with the international PROGRESS study performed a head-to-head comparison of a traditional three-drug HAART regimen and a two-drug NRTI-sparing regimen.
In this open-label Phase III trial, 206 previously untreated participants were randomly assigned to receive lopinavir/ritonavir (400/100 mg twice daily) in combination with either 400 mg twice-daily raltegravir or the once-daily tenofovir/emtricitabine NRTI coformulation (Truvada).
The two study groups were similar at baseline. Most participants (about 85%) were men, the average age was 49 years and three-quarters were white. All had plasma viral load greater than 1000 copies/ml (mean about 20,000 copies/ml) and the average CD4 count was about 300 cells/mm3.
About 9% of study participants dropped out for various reasons, about equally distributed between the two arms. Two individuals in each group stopped early due to side-effects, whilst one in the raltegravir group and two in the tenofovir/emtricitabine group did so due to virological treatment failure.
An intent-to-treat analysis at 48 weeks found that similar proportions of people in both arms achieved viral load below 40 copies/ml: 83% in the raltegravir group and 85% in the tenofovir/emtricitabine group. The minimal difference between the groups indicated that the NRTI-sparing combination was non-inferior to the traditional HAART regimen.
The researchers did not report results according to whether patients started treatment with high or low viral load, which has been shown to affect response to raltegravir in some prior studies.
CD4 cell gains were slightly smaller in the raltegravir group compared with the tenofovir/emtricitabine group – 215 vs 245 cells/mm3, respectively – but again the difference was not statistically significant.
Both study regimens were generally well-tolerated. The most common side-effects, occurring with similar frequency in the raltegravir and tenofovir/emtricitabine arms, were diarrhoea (8% vs 13%, respectively) and elevated cholesterol (8% vs 5%, respectively). One person in each arm showed evidence of drug-resistance mutations.
The researchers acknowledged that 48 weeks might not be long enough to detect long-term problems, and follow-up will continue through to 96 weeks.
The PROGRESS investigators concluded that lopinavir/ritonavir plus raltegravir "resulted in non-inferior efficacy and similar tolerability", compared with the three-drug traditional antiretroviral regimen, and suggested that a two-drug NRTI-sparing regimen "can provide an alternative approach to treatment of antiretroviral-naive patients".
Jacques Reynes's presentation and related abstract are available on the official conference website.
Reynes J et al. Lopinavir/ritonavir combined with raltegravir demonstrated similar antiviral efficacy and safety as lopinavir/ritonavir combined with tenofovir disoproxil fumarate/emtricitabine in treatment-naive HIV-1 infected subjects. Eighteenth International AIDS Conference, Vienna, abstract MOAB0010, 2010.