XIX International AIDS Conference


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MOAB0301 - Oral Abstract Session

Relationship between weight, efavirenz (EFV) concentrations and virologic suppression in HIV+ patients on rifampin (RIF)-based TB treatment in the ACTG 5221 STRIDE study

Presented by Anne F. Luetkemeyer (United States).

A.F. Luetkemeyer1, S.L. Rosenkranz2, D. Lu2, P.S. Lizak3, P. Ive4, S. Swindells5, C.A. Benson6, B. Grinsztejn7, I.M. Sanne4, D.V. Havlir1, F. Aweeka3, Adult AIDS Clinical Trials Group A5221

1San Francisco General Hospital, University of California at San Francisco, Division of HIV/AIDS, San Francisco, United States, 2Statistical Data Analysis Center, Harvard School of Public Health, Boston, United States, 3San Francisco General Hospital, University of California at San Francisco, Department of Clinical Pharmacy, San Francisco, United States, 4University of Witswatersrand, Clinical HIV Research Unit, Johannesburg, South Africa, 5University of Nebraska at Omaha, Infectious Diseases, Omaha, United States, 6University of California at San Diego (UCSD), Division of Infectious Diseases, San Diego, United States, 7Fundação Oswaldo Cruz, STD/AIDS Clinical Research Laboratory, Rio de Janeiro, Brazil

Background: RIF upregulates CYP 450 isoenzymes and can lower EFV exposure, particularly if weight ≥50 kg, However, clinical data have not shown reduced HIV virologic suppression with 600mg EFV+RIF. We conducted a nested PK study to evaluate EFV concentrations and virologic suppression in A5221 patients on EFV(600 mg) and RIF-based TB treatment.
Methods: EFV Cmin was measured using HPLC (LLQ=0.1 µg /ml) in samples from 20-28 hours post-dose at weeks 4,8,16,24 on-RIF, and weeks 4,8 off-RIF, in those with no missed doses for 3 days,. Two-sided Wilcoxon rank-sum tests, logistic regression and Fisher´s Exact tests were evaluated at 5% Type I error rate.
Results: 780 patients from 4 continents received EFV, 543 provided ≥ 1 EFV measurement. Median(IQR) weight was 52.8 kg(48.0,59.5), BMI 19.4kg/m2(17.5,21.6), age 34 ,63% male, race Black(74%), Hispanic(20%), non-Hispanic White(5%), Asian(1%). Weight ≥60 kg on-RIF was associated with lower EFV Cmin, as was weight ≥50 off-RIF(Table). Weight ≥50 and ≥60 were not associated with less frequent HIV virologic suppression (HIV RNA< 400 copies/ml) at week 48. In multivariate models, neither higher weight nor BMI was associated with lower likelihood of virologic suppression. There was no significant difference in the proportion with any subtherapeutic Cmin (< 1) on-RIF(27.3%) vs. off-RIF(26.2%) Median Cmin was higher on-RIF vs. off-RIF in Blacks(2.0 vs 1.6. p< 0.01) but did not differ in Whites(1.3 vs 1.6, p=0.5), Hispanics(1.7 vs. 1.9, p=0.3), and Asians(2.0 vs 1.6, p= 1.0). On-RIF, Blacks had more supratherapeutic Cmin (>4) compared to Whites(22.9% vs 3.9%;p=0.002).

Table 1
[Table 1]

Conclusions: Overall, RIFcoadministration was not associated with lower EFV trough concentrations; patients weighing ≥50 or ≥60 kg had lower EFV Cmin, but there was no association with subtherapeutic Cmin nor virologic suppression.. These data from a multinational, predominantly non-White population do not support guidelines for weight-based dosing of EFV with RIF.

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