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Pilot Study of the Safety and Efficacy of Kaletra as Single Drug HAART in HIV+ ART Naïve Patients: interim analysis of subjects completing at least 24 weeks of a 48 week study
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Reported by Jules Levin
Joe Gathe reported on an unusual study experiment at ICAAC in poster# 2608. It is not recommended that you try this. He conducted a proof of concept open-label pilot study of Kaletra as single drug HAART in HIV-infected treatment-naïve patients. Kaletra was weight-based dosed: LPV/r was dosed 3 caps BID for weight <70 kg (2.2 lbs=kg) and 4 caps BID for weight >70 kg. Gathe reported 24 week results of a 48 week study.
Gathe justified his study: “significant constraints to therapy exist. Toxicity is the leading cause of discontinuation of HAART in the first year. Economic factors ensure millions of eligible subjects do not receive life saving treatment in both developed and underdeveloped countries. Kaletra has ideal characteristics for single drug therapy—it has short term activity comparable to triple drug HAART; 24-hour pharmacokinetics signiicantly above IC50 of wild-type virus; lack of definable genotypic/phenotypic resistance at time of failure in naïve subjects. Economic conditions have led to ADAP formulary problems and higher insurance costs….”
Subjects accrued between March 2002 and March 2003 from a single inner city clinic in Houston. Patients were excluded for life threatening active AIDS defining illness. Viral load was >2000 copies/ml, ART naïve, no CD4 criteria. Primary endpoints include %of patients <400 copies/ml and incidence of adverse events. Intensification was allowed at any point with either tenofovir/3TC or saquinavir.
30 subjects (2 female), 60% white, 20% black, 20% hispanic were enrolled. Average age was 36 years. Plasma HIV RNA average was 262,000 copies/ml (4161-750,000). Average CD4 count was 169 cells. 70% had CD4s <200, 57% had viral load >100,000. 54% had <200 CD4s and >100,000 copies/ml.
PATIENT DISPOSITION AT WEEK 24
Lost to follow-up: 2 Adverse events: 2 (discontinued therapy due to GI intolerability at Wk 12 & wk 1) Deported: 1 (deported at week 16 and had a viral load drop of 2.2 log (259,000 to 1521) Non-adherent: 1 Virologic failure: 1 Hepatitis B: 1 (was found to have HBV and had TDF/3TC added at wk 12)
RESULTS
Mean viral load reduction (as treated) was from 5.41 log at baseline to 2.57 log at week 24. At week 24, 21 of 22 patients (as treated, still on therapy) had <400 copies/ml. By ITT analysis 21 of 30 patients had <400 copies/ml.
Gathe concluded that Kaletra as single drug therapy exhibited comparable virologic efficacy as HAART. Significant toxicity was not seen. Genotypic/phenotypic resistance was not seen. Gathe is planning a follow-up 48 week phase II study to begin enrollment in November 2003.
THIS STUDY IS EXPERIMENTAL. Results from 48 week study with a larger number of patients should be more informative.
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