Pilot study suggests that Kaletra maintenance therapy safe

Maintenance therapy with the boosted protease inhibitor Kaletra alone may be able to offer effective suppression of HIV with little risk of resistance according to a small pilot study published in the March 4^th edition of AIDS.

Kaletra (lopinavir boosted by ritonavir) has been shown to be effective in both treatment-naïve and experienced individuals when included in a HAART combination. The drug has a high genetic barrier to resistance, and is potent, and has favourable pharmacokinetics. Studies have already been conducted looking at the safety and efficacy of weight adjusted Kaletra monotherapy.

Investigators in Miami conducted a small pilot study to explore whether maintenance therapy with Kaletra monotherapy maintains suppression of viral load once this has been achieved using conventional triple drug HAART.

A total of six treatment-naive patients were recruited to the study, and were treated with standard dose Kaletra (lopinavir 400mg boosted by ritonavir 100mg) twice daily with AZT and 3TC for at least 24 weeks with the last three consecutive viral load measurements below 50 copies/ml. Treatment with the nucleoside analogues was then stopped and the six individuals continued treatment with standard dose Kaletra monotherapy.

Intense follow-up was provided, with attending their clinic weekly for the first eight weeks of Kaletra monotherapy, every other week for the next eight weeks, and every four weeks for the next 24 weeks.

At baseline, genotypic resistance tests were performed and these were continued if an individual’s viral load increased to above 1000 copies/ml. At baseline all six patients were fully susceptible to all protease inhibitors and nucleoside analogues.

Four patients maintained a viral load below 1000 copies for the duration of the monotherapy stage of the study. In total 53 viral load measurements were taken, and on 50 occasions (94%), these four patients had a viral load below 400 copies/ml and on 36 out of 53 occasions had a viral load below 50 copies/ml.

Two patients had a less consistent pattern of HIV suppression whilst taking Kaletra monotherapy and had a viral load of 1000 copies/ml or greater on one or more occasion. However, both patients acknowledged poor adherence, and the level of adherence improved in one patient, with his viral load falling to below 400 copies/ml.

Resistance testing failed to find any mutations associated with decreased susceptibility to lopinavir in either individual.

“This study…demonstrates, albeit it in a small number of patients, that [lopinavir/ritonavir] monotherapy maintained viral suppression in most patients for up to six months after viral RNA was suppressed with combination HAART”, write the investigators.

Calling their results “encouraging”, and suggestive, the investigators conclude “successful therapy for HIV-1 infection is possible with more simple regimens. Since the mid-1990s, the simultaneous use of three agents has been and continues to be the standard of care for the treatment of HIV-1 infection. However, more potent antiretroviral agents may obviate the need for three active drugs for all patients. Obviously, large, prospective and controlled studies are needed to investigate this, and are, in fact ongoing. The potential for a significant paradigm shift in antiretroviral therapy exists and is certainly worth exploring.”