A dual-drug regimen of lopinavir/ritonavir (Kaletra) and lamivudine (3TC, Epivir) was found to match up to a triple-drug lopinavir/ritonavir-based regimen, according to study results presented at EACS 2013 in Brussels, Belgium.
The 48-week results of the GARDEL study (short for Global ARV Design Encompassing Lopinavir/Ritonavir and Lamivudine vs. Lopinavir/Ritonavir-Based Standard Therapy) were presented by Pedro Cahn, M.D., Ph.D., of Fundacion Huesped.
The controlled, open-label study followed 426 treatment-naive patients with HIV, all with a baseline viral load over 1,000 copies/mL and no nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) or protease inhibitor (PI) resistance. The patients were then randomized to two groups: 217 were placed in the dual therapy (DT) arm, in which they initiated treatment with lopinavir/ritonavir plus lamivudine. The remaining 209 were placed in the triple therapy (TT) arm, in which they initiated treatment with lopinavir/ritonavir plus a fixed-dose combination drug containing either lamivudine or emtricitabine (FTC, Emtriva) and an investigator-selected NRTI.
The study included participants from Argentina, Chile, Mexico, Peru, Spain and the U.S. Baseline characteristics were similar for both groups. The DT group had a median age of 34 and 83.6% were male, while the TT group had a median age of 35 and 83.1% were male. Mode of transmission was around 60% men who had sex with men and around 35% heterosexual across both groups.
In terms of baseline lab values, both groups had a median viral load of about 79,000 copies/mL. The median CD4+ cell count was 319 cells/mm3 for the DT group and 329 for the TT group. A little more than 21% of the DT group and 18.8% of the TT group had a baseline CD4+ cell count below 200.
At week 48 after initiating treatment, 88.3% of the DT group had a viral load less than 50 copies/mL compared to 83.7% in the TT group; the difference was not statistically significant. In particular, Cahn noted, when analyzing those who had a baseline viral load above 100,000 copies/mL, 87.2% of the DT group had a viral load less than 50 copies/mL at week 48 compared to 77.9% in the TT group.
The DT group had fewer discontinuations due to safety and tolerability. Only two patients (0.9%) in the DT group discontinued because of death or an adverse event: One discontinuation was the result of death due to sepsis, which was unrelated to therapy, and the other was due to nephrotic syndrome. On the other hand, 10 patients (4.9%) in the TT group discontinued because of an adverse event: two for rash, three for anemia and five for gastrointestinal intolerance.
Protocol-defined virologic failure, which was defined as having a viral load over 400 copies/mL at week 24 or a viral load over 50 at week 48, occurred at similarly low rates among both groups: 4.6% for the DT group and 5.9% for the TT group. Failure did not result in PI resistance, Cahn said, preserving a wide range of drugs for second-line therapy.
Overall, with these results, Cahn concluded that a dual-treatment regimen of lopinavir/ritonavir plus lamivudine warrants further research and consideration as a first-line option for treatment-naive patients.
However, lopinavir/ritonavir is not presently a recommended first-line drug in any major HIV treatment guidelines. As Paul Sax, M.D., opines in his analysis of this study, the findings are unlikely to immediately influence clinical practice. However, they do still mark a "paradigm-shifter" inasmuch as this is the first fully powered study to find that a two-drug regimen actually can potentially be better than a three-drug regimen, Sax suggests.