Lopinavir/Ritonavir Monotherapy Is Noninferior to Standard ART in Confirmatory Study

Becky McCall

November 18, 2009

November 18, 2009 (Cologne, Germany) — A comparison between a simplified regimen of lopinavir/ritonavir (Kaletra) monotherapy and standard antiretroviral therapy (ART), consisting of a protease inhibitor (PI) and 2 nucleoside reverse transcriptase inhibitors (NRTIs), shows that lopinavir/ritonavir is noninferior to the standard of care.

Pedro Cahn, MD, chief of infectious diseases at Buenos Aires University Medical School, Hospital Juan Fernandez, in Argentina, who presented results at the 12th European AIDS Conference/European AIDS Clinical Society (EACS), told Medscape HIV/AIDS that the study addresses the ongoing question of if and when monotherapy can be used.

This year, for the first time, lopinavir/ritonavir monotherapy appeared in the EACS guidelines for the treatment of HIV-infected patients who already have viral suppression.

"Clinicians most often use monotherapy to save money on unnecessary drugs or to spare toxicity. The usual combination therapy is a nonnucleoside, for example efavirenz (Sustiva), nevirapine (Viramune), or a ritonavir-boosted PI; in both cases, 2 NRTIs are added," Dr. Cahn observed.

Patients in the 1-year randomized open-label multicenter study were HIV-1-infected adults receiving their first PI-containing treatment. This regimen was based on a ritonavir-boosted PI plus 2 NRTIs (standard of care), and patients were randomized to continue as such or to simplify their regimen to lopinavir/ritonavir monotherapy. The mean duration of HIV-1 disease was 3.3 years.

"Trial patients had undetectable [viral loads] for 6 months prior to randomization, with a viral load of less than 50 copies/mL, a CD4 count above 100 cells/mL, and no active or acute disease," said Dr. Cahn.

Of the 80 patients in the intent-to-treat population, 41 (51.2%) were randomized to lopinavir/ritonavir and 39 (48.8%) were randomized to continue with their established ART regimen. Nine (11.2%) patients discontinued the trial — 2 in the lopinavir/ritonavir group and 7 in the standard ART group.

After randomization, the viral load was controlled; if patients experienced rebound, the 2 NRTIs were reintroduced. This occurred in 10% of patients receiving monotherapy and reintroduction was accomplished successfully without harm.

Dr. Cahn said that monotherapy might be an option for some patients. "The results were quite encouraging and confirm data from other authors who have worked with lopinavir/ritonavir monotherapy. I wouldn't say this monotherapy should be the standard of care for everybody, but it is a good option for patients who cannot deal with 2 NRTIs or the toxicity and tolerability issues related to them."

He also added that, in particular, monotherapy is an option in regions of the world where drug access is difficult and there is a shortage of funding.

"We can claim noninferiority for the strategy because we had preplanned the reintroduction of 2 NRTIs if required. If this had not been planned, then we would have said that the 2 strategies are almost similar but triple therapy is better," added Dr. Cahn.

José Arribas, MD, from the HIV Care Unit, Hospital La Paz, in Madrid, Spain, has vast experience with lopinavir/ritonavir monotherapy to maintain viral suppression in HIV-infected patients. These study results confirm those found in the OKO4 trial on maintenance of virological suppression, he observed.

"This adds important evidence that supports the fact that if patients do fail [monotherapy], then this is reversible and patients can be reintroduced to the standard of care. Also, we often have to treat patients for decades; for the patient, it is better toxicity-wise to treat with 1 drug than 3."

Dr. Arribas added that monotherapy might have implications for adherence. "Monotherapy is less forgiving because if a patient is only taking a boosted PI and they miss a dose, then there is a higher chance of rebound. This is not an improvement in convenience."

Dr. Cahn reports being a speaker for Abbott and a member of an Abbott advisory board. Dr. Arribas reports receiving financial support from Abbott.

12th European AIDS Conference/European AIDS Clinical Society (EACS): Abstract 7.5. Presented November 12, 2009.