Kaletra monotherapy: unorthodox but effective regimen challenges the rules

Nine years after the treatment of HIV with a single drug was discredited in the Delta study, monotherapy resurfaced this week at the 43^rd Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago. This time it was monotherapy with a single potent protease inhibitor, chosen because the high drug levels achieved seem to reduce the risk of resistance.

Lopinavir/ritonavir (Kaletra) monotherapy proved suprisingly effective in a study of thirty patients carried out by Dr Joe Gathe, a Houston physician. Only one patient failed to achieve undetectable viral load after 24 weeks. This patient had begun therapy with a viral load of 500,000 copies, and despite adequate trough levels of lopinavir at week 32, the patient’s viral load remained detectable. No evidence of protease inhibitor resistance was detected using either a genotypic or phenotypic resistance test.

Two patients discontinued due to adverse events, one discontinued due to non-adherence, one patient added tenofovir and 3TC due to a hepatitis B diagnosis and three patients were lost to follow-up. Of the remaining 22, all but one had viral load below 400 copies/ml at week 24. The mean baseline viral load was 262,000 copies/ml and the mean viral load reduction at week 24 was –2.8 log₁₀ copies/ml, an impressive performance for a single agent. Participants had advanced HIV disease in the main; 21 had baseline CD4 counts below 200 cells/mm³, and 16 had CD4 counts below 200 and viral load above 100,000 copies/ml at baseline. The average CD4 cell gain was 214 cell/mm³ at week 24.

The study will continue to follow patients for 48 weeks, and a further study is planned.

The study was conducted at an inner city clinic in Houston, Texas, and the authors of the study emphasised that access to treatment is not just an issue for the developing world. As pressure on state drug assistance programmes and other means of paying for treatment grows, approaches to treatment which can cut its cost will begin to be taken more seriously in the world’s richest country too.

Reference

Gathe JC et al. Single drug HAART proof of concept study. Pilot study of the safety and efficacy of Kaletra (LPV/r) as a single drug HAART in HIV+ naïve patients. Interim analysis of subjects completing at least 24 weeks of a 48 week study. 43^rd ICAAC, Chicago, abstract 2608, 2003.