AEGiS-14IAC: NEKA study: NRTI-sparing regimen.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

NEKA study: NRTI-sparing regimen.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeB9021)

Negredo E, Bonjoch A, Sirera G, Puig J, Videla S, Kurowski M, Bonafont X, Ruiz L, Clotet B
Lluita contra la SIDA Foundation. Germans Trias i Pujol Hospital, Barcelona, Spain

BACKGROUND: NRTIs have been recently linked to mitochondrial toxicity (MT). Nevirapine (NVP) has been associated with a favourable lipid profile while lopinavir/ritonavir (LPV/rtv) increases cholesterol and triglyceride levels. OBJECTIVES: To study the efficacy of LPV/rtv 400/100mg + NVP 200mg, BID, and the pharmacokinetic (PK) interactions between both drugs. To assess if NVP counteracts the LPV/rtv effect on lipid metabolism and if this strategy reverses MT.

METHODS: A total of 30 ARV-experienced but LPV/rtv-naïve patients (pt) with VL<80copies/ml during > 9 months (mo) were included in this pilot study and randomised to LPV/rtv + NVP (Arm A, n=16) or to LPV/rtv + 2 NRTIs (the previous NRTIs) (Arm B, n=14). HIV RNA, CD4+, fasting lipid metabolism, hepatic profile and LPV through levels (Cmin, in 10 pt) were performed every 3mo and mitochodrial (m) DNA/ nuclear (n) DNA ratio every 6mo.

RESULTS: At 6mo, both arms mantained viral suppression although CD4 rose significantly only in group A (from 552 to 758 cel/mm³ in group A and from 640 to 668 cel/mm³ in B). Neither significant changes in mean GPT and GGT nor in triglyceride levels were seen in any group, while an increase in mean cholesterol was observed in both groups (from 205 to 250 mg/dl in group A and from 179 to 226 mg/dl in B). Only one pt from group A was lost to follow-up. Mean LPV Cmin levels were similar between both arms at steady state conditions: 4924 ng/ml in group A (range: 2130-6940 ng/ml) vs 4432 ng/ml in group B (range: 3350-6120 ng/ml); only one patient of each group showed LPV Cmin levels <3500 ng/ml. mDNA/nDNA ratios are currently being analysed.

CONCLUSIONS: At 6mo the switch to an NRTIs-sparing regimen consisting on LPV/rtv (3 pills) + NVP (1 pill) BID, seems to be safe and, at least, equally potent than LPV/rtv + 2NRTIs. However, NVP was not able to counteract the lipid abnormalities related to LPV/rtv. This study was partially supported by Abbott and Boehringer Ingelheim Lab.

Keywords: AEGIS, Ritonavir, Nevirapine, HIV Protease Inhibitors, Pyrimidinones, Anti-HIV Agents, HIV Infections, HIV, HIV Protease, HIV Seropositivity, lopinavir, Human

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