July 14, 2003
There has always been a keen interest in trying to identify a simple and compact treatment regimen for the long-term management of HIV infection. Not long after protease inhibitor (PI)-based triple-drug therapy was developed, studies were done to see if patients who had achieved viral suppression could simplify their treatment regimens to a single agent. In one study, patients with undetectable HIV-RNA levels on treatment with AZT (zidovudine, Retrovir), 3TC (lamivudine, Epivir) and indinavir (IDV, Crixivan) were randomized to either indinavir monotherapy, AZT and 3TC together, or continued triple therapy. Unfortunately, a higher rate of virologic failure within 16 weeks of switching from triple therapy to indinavir monotherapy was noted and the study was halted prematurely (Havlir, New England Journal of Medicine 1998; 339:1261-8).
At this conference, a pilot study of a similar simplification strategy was reported. However, in the case of this study, a ritonavir (RTV, Norvir)-boosted indinavir regimen was simplified to boosted indinavir alone. Twelve patients with plasma HIV-RNA levels of <50 copies/mL for more than three months while on indinavir/ritonavir had their NRTIs stopped and were continued on indinavir/ritonavir only. At 48 weeks of follow up there were no cases of virologic failure and only occasional low level viral load blips were seen. The dosage of ritonavir was either 100 mg or 200 mg BID and the doses of indinavir ranged from 400 mg BID to 800 mg BID. Individual patient dosages were determined based on therapeutic drug monitoring -- the goal was to maintain indinavir Cmin levels between 500 and 2000 nanomole/liter.
The major problem with this strategy was the significant rate of kidney problems. There were three cases of nephrolithiasis and one case of creatinine elevation related to boosted-indinavir "mono" therapy. These renal toxicity problems associated with boosted-indinavir regimens have been noted before and may be one of the reasons for the limited use of this regimen.
This very interesting study is the first prospective study that I am aware of that reports long-term data on the use of a boosted PI alone for the management of HIV infection. I am aware of several other prospective pilot studies that are underway which test lopinavir/ritonavir (LPV/r, Kaletra) in the same fashion. If these findings can be confirmed by other investigators, they may spark renewed interest in induction-maintenance approaches for the long-term management of HIV infection.