In the OKO4 study, 198 patients with long-term virologic suppression and no history of protease inhibitor (PI) resistance were randomized to lopinavir/ritonavir (LPV/r, Kaletra) + two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or maintenance therapy with lopinavir/ritonavir alone. As presented at the XVI International AIDS Conference in Toronto this past summer, virologic suppression rates at 48 weeks for the two strategies were equal, with the caveat that patients on the monotherapy arm were allowed to resume two NRTIs in case of virologic rebound. The presentation by Jose Arribas et al¹ at the 14th Conference on Retroviruses and Opportunistic Infections describes the resistance analysis from the study.

In the monotherapy arm, 11% of the study participants qualified for genotype testing, versus 4% in the triple therapy arm (P = .07). The rate of detected resistance mutations was low, and equal, in both arms -- 2% with PI mutations and 1% with reverse transcriptase mutations.

The specific PI mutations detected were as follows:

Phenotype testing showed that resistance to lopinavir was at a very low level, and that viruses retained susceptibility to saquinavir (SQV, Invirase), amprenavir (APV, Agenerase), atazanavir (ATV, Reyataz), tipranavir (TPV, Aptivus) and darunavir (TMC114, Prezista).

The results of this analysis demonstrate that for selected patients, maintenance monotherapy with lopinavir/ritonavir is generally associated with a low risk of virologic rebound and PI resistance. In addition, treatment options are maintained if virologic rebound is acted on quickly, as was done here. Whether this strategy can or should be applied to a non-study population is still debatable, as triple therapy with current NRTIs, such as tenofovir/emtricitabine (TDF/FTC, Truvada) or abacavir/lamivudine (ABC/3TC, Epzicom, Kivexa), is far safer than before, with a low risk of lipoatrophy and other complications mediated by mitochondrial toxicity. It may turn out that the best setting for lopinavir/ritonavir monotherapy is one in which safe NRTI options are unavailable or limited.

Footnote

1. Arribas J, Pulido F, Delgado R, et al, and OK04 Study Group. Drug resistance outcomes at 48 weeks in the OK04 Trial: a comparative trial of single-drug maintenance therapy with lopinavir/ritonavir vs triple therapy with LPV/r. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Abstract 638.