Efavirenz treatment results in a significantly higher rate of viral suppression after 48 weeks when compared to lopinavir/ritonavir, investigators of a randomised study among Mexican patients with very advanced HIV disease reported on Tuesday at the XVII International Conference on AIDS in Mexico City.
Like many developing countries, the vast majority of people with HIV in Mexico are diagnosed with very advanced HIV, having symptomatic disease and a very low CD4 cell count (3). Seventy-seven per cent of a large cohort of patients in Mexico had a CD4 count below 100 cells/mm3 at diagnosis, said Dr Juan Sierra-Madero of Mexico's National Institute of Medical Sciences, introducing the study’s purpose. Studies of treatment strategies or new agents needed to focus on this group of patients in low and middle-income countries, he said, due to the poor rate of diagnosis in patients with less advanced HIV.
Although there are data on the performance of various antiretroviral treatment regimens from a large randomised study conducted in patients with advanced HIV disease (ACTG 5142) the average CD4 cell count in that study was around 180 cells/mm3 and only one-third of patients had a baseline CD4 count below 100 cells/mm3.
The study recruited 189 treatment-naïve people with HIV who had CD4 cell counts below 200 cells/mm3 at 11 centres in Mexico. Participants were randomised to receive efavirenz (n=95) or lopinavir/ritonavir (n=94), each with two nucleoside reverse transcriptase inhibitors (AZT and 3TC, dosed as Combivir).
At baseline, patients receiving efavirenz had 64 CD4 cells/mm3 compared with 52 cells/mm3 for the protease inhibitor group. Forty-two per cent of the efavirenz group had a CD4 count below 50 cells/mm3 compared to 45% of the lopinavir/ritonavir group.
At week 48 and using an intention-to-treat analysis, 70% of patients in the efavirenz group had HIV RNA of 50 copies/ml compared with 53% in the protease inhibitor group (p=0.0141). Seventy-one per cent of the efavirenz group were still on the assigned treatment at week 48, compared to 58% of lopinavir/ritonavir group, also a significant difference.
However, when the difference between patients was assessed according to the proportions with viral load below 400 copies/ml, there was no significant difference in virological suppression at week 48 (73% vs 65%, p=0.2), indicating that most virological failures in the lopinavir/ritonavir arm occurred as cases of viral load rebound above 50 copies/ml but below 400 copies/ml.
The study was designed as a non-inferiority study. Statisticians had calculated that, given the sample size, the upper and lower limit of the 95% confidence interval for achieving non-inferiority was 12%. In this study the difference in virological suppression below 50 copies/ml at week 48 between the two arms was 17%, with a 95% confidence interval of -3.5% - +31%. Although the confidence intervals are wide, Dr Sierra Madero said that the finding showed that efavirenz was superior to lopinavir/ritonavir in this population.
The mean CD4 cell count increase was 156 cells/mm3 in the efavirenz group and 170 cells/mm3 in the lopinavir/ritonavir group.
More patients discontinued treatment in the protease inhibitor group (34% vs 27%), and this difference was driven equally by virological failure and adverse events. Serious adverse events were more frequent in the lopinavir/ritonavir group (22.3% vs 17.8%).
The protease inhibitor regimen was also associated with higher increases in cholesterol and triglycerides (p=0.24 and p=0.0036, respectively).
The authors conclude that an efavirenz-containing antiretroviral therapy regimen has superior efficacy to one containing lopinavir/ritonavir in treatment-naïve people with advanced HIV infection.
Sierra Madero J et al. A prospective, randomized, open label trial of efavirenz versus lopinavir/ritonavir based HAART among antiretroviral therapy naïve, HIV infected individuals presenting for care with CD4 cell counts XVII International AIDS Conference, Mexico City, abstract TUAB0104, 2008.