Background: Combinations of new drugs could prove effective in pts patients (pts) who have failed multiple lines of antiretroviral therapy, provided that interactions do not alter pt exposure to the drugs. Tenofovir (TDF) and a Ritonavir (RTV) enhanced Atazanavir (ATV) regimen were combined as salvage therapy. The pharmacokinetic (pk) part of this study is described.

Methods: A prospective, randomized, open-label, multicentre trial in pts pts  with CD4+< 500/mm³ and plasma HIV RNAviral load  (pVL)> 10,000 copies/ml after failure of regimen lines containing at least 2 PIs and 1 NNRTIcontaining regimen. For the first 2 weeks (wks), pts pts  were randomized to unchanged PI and NRTIs (group 1) or to a combination of receive either once a day either: ATV (300 mg once a day), combined to RTV (100 mg once a day), andwith unchangedfailing NRTIs (group 12). , or failing PI and NRTIs maintained TDF 300 mg (group 2). From wksweeks 2­–26, all pts pts  received ATV/RTV, and TDF 300 mg (once a day) andco-administered with 2 - recycled nucleoside analogsNRTIs. Fifty-three (25 53) pts pts were enrolled in each treatment armrandomized in the study. Samples for ATV and RTV pk were drawn aton day 15  weewk 2 and wk on week 6 in 11 patients fromof  group 2.

Results: Ten (10) pts (x malesmale pts (meanmean 45 yearsear old) completed the pk study. At baseline, median CD4+ was 117/mm³ and median pVLHIV RNA was 5.1 log₁₀ copies/ml. Average mMedian number of antiretrovirals taken prior to randomization was 11. ATV and RTV pk parameters (geometric means at weewk 2 and weewk 6 and their ratio and geometric mean (standard 90% CI) ratios (90% CI), median and range offor Tmax) were as follows:

	ATV				RTV
	wk 2	wk 6	wk 6/wk 2		wk 2	wk 6	wk 6/wk 2
Cmax (ng/ml)	4,422	3190	0.72 (0.50–1.05)		886	642	0.72 (0.43–1.21)
Tmax (h)	3 (2–5)	5 (1–5)	-		3 (2–8)	3 (0-5)	-
AUC24 (ng.h/ml)	46,073	34,459	0.75 (0.58–0.97)		7,011	5217	0.75 (0.44–1.24)
Cmin (ng/ml)	636	491	0.77 (0.54–1.10)		43	39	0.91 (0.73–1.13)
C24 (ng/ml)	696	513	0.74 (0.53–1.02)		50	44	0.88 (0.69–1.13)

 

Conclusions: At wk 2, ATV pk parameters when combined with RTV are in agreement with data obtained in healthy volunteers. After TDF introduction, both ATV and RTV parameters seemed to be reduced. These Ppreliminary findings suggest that decrease in the reduced ATV concentrations at wk 6 could be the result fromof loweredreduced RTV concentrations, even though the differences on most parameters did not reach statistical significance. The impact of TDF on ATV pk when given alone isare unknown. Mechanism of this non metabolic interaction, is unclear and could occur most likely to occur at the absorption level, needs further investigationsite.