A nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen consisting of Kaletra (lopinavir and ritonavir) plus Isentress (raltegravir) is comparable with a standard regimen consisting of Kaletra plus Truvada (tenofovir and emtricitabine) in people living with HIV starting antiretroviral (ARV) therapy for the first time, according to 48-week study results reported Monday, July 19, at the XVIII International AIDS Conference in Vienna.
Standard regimens for treatment-naive people living with HIV usually consist of two NRTIs plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Though such pairings are preferred, based on long-term safety and efficacy data reviewed by the U.S. Department of Health and Human Services in its HIV treatment guidelines, there has been an interest in using NRTI-sparing regimens, notably for those who experience side effects while using approved options or are believed to be at a high risk for NRTI-related toxicities (such as kidney damage).
Early data from the 96-week PROGRESS study, reported by Jacques Reynes, MD, of the University Hospital Center of Montpellier, France, and his colleagues, illustrate the potential of one such NRTI-sparing regimen. The open-label study—meaning everyone knows which drugs they are taking—has enrolled 101 patients to receive Kaletra plus twice-daily Isentress and 105 patients to receive Kaletra plus Truvada. The primary endpoint of the study is the percentage of patients with viral loads below 40 copies—undetectable—after 48 weeks of treatment.
Viral loads averaged 18,000 copies upon entering the study; CD4 counts averaged 293.5 cells. Approximately 85 percent of the study participants were men and approximately 75 percent were white.
A similar proportion of study volunteers in each arm discontinued treatment prematurely during the initial 48-week follow-up period: 12 percent in the Kaletra/Isentress group and 11 percent in the Kaletra/Truvada group.
A similar proportion of patients had undetectable viral loads when treated with Kaletra/Isentress, compared with Kaletra/Truvada. About 83 percent had viral loads below 40 copies in the Kaletra/Isentress group, Reynes reported, compared with 85 percent in the Kaletra/Truvada group.
The average CD4 increases through 48 weeks were also similar. There was a 215-CD4 cell increase in the Kaletra/Isentress group, compared with a 245-CD4 cell increase in the Kaletra/Truvada group. This difference was not statistically significant, meaning that it could have been a result of chance.
The authors also noted that no new protease mutations associated with Kaletra resistance developed in the study in either treatment group. An Isentress-associated resistance mutation was observed in one patients receiving Kaletra/Isentress, whereas an emtricitabine-associated resistance mutation was observed in one patients receiving Kaletra/Truvada.
Moderate-to-severe drug-related adverse effects were similar in both groups. The most common side effect was diarrhea, occurring in 8 percent of those receiving Kaletra/Isentress versus 13 percent of those receiving Kaletra/Truvada—this difference was not statistically significant. Lipid elevations—notably average increases in cholesterol and triglyceride levels—were observed more frequently in the Kaletra/Isentress group. Elevations in creatine phosphokinase levels were also more likely to occur among those receiving Kaletra/Isentress.
“The 48-week PROGRESS study results, while not definitive, suggest that the nucleoside-sparing HIV regimen of Kaletra and Isentress may be an alternative treatment option for patients new to HIV therapy, when compared to a standard HIV regimen,” Reynes concluded. “This further advances our research into new HIV treatment classes and explores the use of alternative drug combinations for patients.”