AEGiS-14IAC: Pharmacokinetic (pk) interaction between lopinavir/ritonavir (LPV/r) and amprenavir (APV) does not affect virologic response to the combination of LPV/r, APV and RTV in HIV-infected patients (pts) with multiple treatment failure (Puzzle 1-ANRS104 Study).

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Pharmacokinetic (pk) interaction between lopinavir/ritonavir (LPV/r) and amprenavir (APV) does not affect virologic response to the combination of LPV/r, APV and RTV in HIV-infected patients (pts) with multiple treatment failure (Puzzle 1-ANRS104 Study).

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeB9023)

Raguin G, Taburet AM, Chene G, Morand-Joubert L, Droz C, Vincent I, Clavel F, Girard PM
Hopital Saint-Antoine, Paris, France

BACKGROUND: A combination of APV, LPV and RTV could prove effective in pts failing multiple antiretrovirals (ARV) provided that pk interactions between APV and LPV have no negative effect on virologic response.

METHODS: A prospective, randomized, open-label, multicentre trial in pts with CD4+<500/mm³ and plasma HIV RNA (pVL)<gl>10.000 copies/ml after at least 2 PIs and 1 NNRTI. For the first 2 wks, pts were randomized to receive either: LPV/r (gr1), APV (1200mg/d) + RTV (200mg/d) (gr2), LPV/r + RTV (200mg/d) (gr3), APV (1200mg/d) + RTV (400mg/d) (gr4). From wks 2 to 26, all pts received APV and LPV/r with an additional boost of 200mg/d of RTV for gr 3 and 4.

RESULTS: 40 pts were randomized, 37 started treatment. At baseline, median CD4+ was 207/mm³, median pVL 4.7 log₁₀ copies/ml, median nb of PI mutations: 7. Average nb of ARV taken prior to randomization was 7.7. Median APV and LPV plasma trough conc. were: [table: see text] As previously described (Croi2002), median APV Cmin was significantly lower after addition of LPV/r (p=0.003). There was no significant impact of APV on LPV Cmin. Plasma unbound APV fraction at wk 2 and 6 was 9.4 and 12.4% (p=0.004), not related to AAG. The pk interaction did not affect the virologic response: median pVL (log₁₀ copies/mL) changes at wk26 in pts with the additional boost of RTV (400 mg/d) was -2.5 vs -1.4 (p=0.02) in those with 200 mg/d RTV. 61% (11/18) reached a pVL<50 cps/ml vs 32% (6/19), respectively (p=0.07).

CONCLUSIONS: In pts having failed multiple antiretrovirals, a combination of APV, LPV/r with an additional boost of RTV shows a significant virologic response despite a pk interaction between LPV and APV that might result, at least in part, from APV plasma protein binding displacement by LPV.

Keywords: AEGIS, Ritonavir, Pyrimidinones, HIV Infections, Sulfonamides, Drug Interactions, HIV Seropositivity, lopinavir, VX 478, Human, virology, pharmacokinetics

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LbPeB9023