PI Monotherapy Tested in Patients with Well-controlled HIV Infection

By Karla Gale

For HIV-infected patients with low viral loads while on HAART, switching to monotherapy with ritonavir-boosted indinavir may control disease progression for some time, results of a small pilot study in Europe suggest.

These findings do not imply that monotherapy with protease inhibitors (PI) should be used in clinical practice, the study investigators warn. However, they do suggest that clinical trials are warranted.

Previous attempts to treat with the PI indinavir alone have failed, and other investigators have warned against "oversimplifying" HIV treatment regimens.

But in their report in the April 9th issue of AIDS, Dr. Pietro L. Vernazza and his group point out that ritonavir-boosted indinavir treatment increases the efficacy of the single PI by increasing its concentration in blood and its ability to penetrate into cerebrospinal fluid and the genital tract.

Dr. Vernazza, at Cantonal Hospital St. Gallen in Switzerland, and his group theorized that ritonavir-boosted indinavir could limit side effects associated with HAART, reduce costs and improve adherence.

Their study included 12 patients whose blood HIV-RNA levels had been maintained at < 50 copies/mL for at least 3 months and who had no history of treatment failure while under treatment with two NRTIs and indinavir/ritonavir. The NRTIs were discontinued and the dose of indinavir was adapted to achieve trough levels of 500 to 2000 nM/L (400 to 800 mg b.i.d.).

HIV-RNA levels were checked monthly, therapeutic drug monitoring was performed, and special measures were used to increase drug adherence. One patient developed CNS T-cell lymphoma and died even though his HIV levels remained < 20 copies/mL and CD4 cell count > 650/µL.

In the remaining 11 patients, HIV levels remained > 400 copies/mL or never dropped below 200 copies/mL on three consecutive testings during the initial 48 weeks. They remained on the regimen during a median follow-up of 78 weeks. Out of 114 repeat measurements, there were four "blips" in which HIV-RNA exceeded 100 copies/mL.

"Patients who never had a blip in viral load are now followed every six weeks," Dr. Vernazza told Reuters Health.

The original HAART regimen had resulted in increased blood lipid levels, he noted. Despite the association between lipodystrophy and PI treatment, "a comparison of body fat composition at baseline and week 48 showed no change in body fat composition," he said.

"The side effects of the regimen were significant, so I assume that physicians would not jump on this treatment regimen," he continued. But for patients who tolerate ritonavir-boosted indinavir well, "such a treatment simplification might be attractive."

He cautioned that the results of this trial should not be extrapolated to the induction phase of HIV therapy or to other ritonavir-boosted PI regimens.

AIDS 2004;18:955-957.