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 HIV and Coverage of the
XVIII International AIDS Conference
(AIDS 2010)  July 18 - 23, 2010, Vienna, Austria
NRTI-sparing Regimen of Lopinavir/ritonavir plus Raltegravir Works as Well as Traditional 3-drug HAART

SUMMARY: An antiretroviral therapy (ART) regimen consisting of the protease inhibitor lopinavir/ritonavir (Kaletra) plus the integrase inhibitor raltegravir (Isentress) suppressed HIV viral load as well as a traditional 3-drug highly active ART (HAART) combination, while avoiding potential adverse side effects of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), according to study findings reported this week at the XVIII International AIDS Conference (AIDS 2010) in Vienna.

By Liz Highleyman


HAART regimens to date have typically included a protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a "backbone" of 2 NRTIs. Development of new drug classes -- including integrase inhibitors that prevent HIV from inserting its genetic material into host cells -- offers new options for constructing potent combination regimens.

Jacques Reynes and fellow investigators with the PROGRESS (PROtease/InteGRasE Simplification Study [aka M10-336]) team designed this open-label Phase 3 trial to compare a traditional 3-drug HAART regimen and a 2-drug NRTI-sparing combination.

A total of 206 treatment-naive participants were randomly assigned (1:1) to receive 400/100 mg twice-daily lopinavir/ritonavir combined with either 400 mg twice-daily raltegravir -- but no NRTIs -- or else once-daily tenofovir/emtricitabine (Truvada).

Most participants (about 85%) were men, 75% were white, 21% were black, and the average age was 49 years. All had plasma viral load > 1000 copies/mL -- with a mean of about 20,000 -- and the average CD4 count was nearly 300 cells/mm3.

The primary endpoint of undetectable viral load (< 40 copies/mL) at 48 weeks was reported at AIDS 2010, but follow-up is continuing through 96 weeks.


In a 48-week intent-to-treat TLOVR analysis, 83.2% of participants in the raltegravir group and 84.8% in the tenofovir/emtricitabine group achieved undetectable viral load.
This difference of -1.6% easily fell within the predefined non-inferiority thresholds of 20% and 12%, allowing investigators to conclude that the NRTI-sparing combination was non-inferior to the traditional HAART regimen.
Raltegravir suppressed viral load in more patients during the early treatment period -- with significant differences at weeks 2, 4, 8, and 16 -- but tenofovir/emtricitabine caught up by week 24.
CD4 cell counts rose by statistically similar amounts at all time points, ending with gains of 215 cells/mm3 in the raltegravir group and 245 cells/mm3 in the tenofovir/emtricitabine group.
Both study regimens were generally well-tolerated.
8% of participants in the raltegravir arm and 11% in the tenofovir/emtricitabine arm discontinued the study for any reason, not a significant difference.
2 patients in both groups quit due to adverse events; 1 in the raltegravir group and 2 in the tenofovir/emtricitabine group did so due to virological failure.
The most common side effects, occurring at similar rates in the raltegravir and tenofovir/emtricitabine arms, were diarrhea (8% vs 13%, respectively) and elevated cholesterol (8% vs 5%, respectively).
Total cholesterol, HDL "good" cholesterol, and triglyceride levels increased by a larger average amount, and in more patients, in the raltegravir arm.
1 person in each arm had evidence of drug resistance mutations, but there were no new protease resistance mutations.

Based on these findings, the PROGRESS investigators concluded that lopinavir/ritonavir plus raltegravir "resulted in non-inferior efficacy and similar tolerability as a traditional 3-drug antiviral regimen."

"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 said in a press release issue by Abbott, the maker of lopinavir/ritonavir.

Investigator affiliations: Hôpital Gui de Chauliac, Montpellier, France; Abbott, Abbott Park, IL; Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain; Innovative Care PSC, Bayamon, Puerto Rico; Therapeutic Concepts, Houston, TX.


J Reynes, A Lawal, F Pulido, and others. 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: PROGRESS 48 week results. XVIII International AIDS Conference. Vienna, July 18-23, 2010. Abstract MOAB0101.

Other Source
Abbott. Abbott's PROGRESS Study of Kaletra and Isentress Compared with a Standard HIV Regimen Meets the Pre-Specified Primary Efficacy Endpoint. Press release. July 19, 2010.












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