AEGiS-15IAC: Indinavir/ritonavir 800/100mg bid and efavirenz 600mg qd in patients with combination nucleoside failure: 96 week outcomes of HIV-NAT 009.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Indinavir/ritonavir 800/100mg bid and efavirenz 600mg qd in patients with combination nucleoside failure: 96 week outcomes of HIV-NAT 009.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrB1084)

Boyd MA, Siangphoe U, Duncombe CJ, Chomchey N, Ubolyam S, Stek M, Ruxrungtham K, Lange JM, Cooper DA, Phanuphak P
HIV-NAT, Bangkok, Thailand

BACKGROUND: Nucleoside reverse transcripatse inhibitor (NRTI) class sparing is attractive for patients with NRTI failure or toxicity.

METHODS: This single arm, open label study switched patients failing NRTIs (defined as HIV RNA >1000 copies/ml on combination NRTI therapy) to IDV/r 800/100mg bid + EFV 600mg qd. Efficacy was assessed by HIV RNA and CD4 responses. Blood samples were drawn from fasted patients. Analysis is by intention to treat. Medians [IQR] and means [SD] are expressed.

RESULTS: The study enrolled 61 patients (23 females). Mean NRTI exposure was 4.1 [1.2] years. Baseline median log₁₀HIV RNA was 4.09 [3.75 - 4.61] copies/ml, and median CD4 169 [59.5 - 277] cells/mm³. At week 96 median log₁₀HIV RNA decline was -2.19 [-2.81 - 1.85], median CD4 rise was 146 [66.5 - 232], and 42 patients (69%) had HIV RNA<50 copies/ml. Ten (16.4%) permanently ceased therapy (1 AIDS, 5 virological failure, 2 GI intolerance, 2 lost to follow up). Temporary drug interruptions occurred in 16 patients (26.2%) from study drug related adverse events. Twenty nine study drug related serious adverse events occurred in 24 patients, predominantly hypertriglyceridemia (15/29 (52%) events). Median TC/HDL-c ratio rose significantly (0.49 [0.33-1.78] mmol/L, p<0.01) as did blood glucose (0.17 [- 0.11-0.67] mmol/L, p<0.01). Ten patients underwent IDV dose reduction, mainly due to nephrotoxicity (8/10). Median ALT decreased after switch (-10 [-32.5 - -2] units/L (p<0.01).

CONCLUSIONS: IDV/r 800/100mg bid + EFV 600mg qd gave a durable response in these NRTI failures and was reasonably well tolerated. A pro-atherogenic metabolic profile developed. Liver toxicity declined after switch. Nephrotoxicity occurred requiring IDV dose reductions. Further study of reduced indinavir doses is warranted in order to minimize IDV related adverse events.

Keywords: AEGIS, Indinavir, Ritonavir, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Oxazines, HIV Protease Inhibitors, HIV Infections, HIV-1, Nucleosides, Zidovudine, Anti-HIV Agents, Lamivudine, Stavudine, Didanosine, Dideoxynucleosides, efavirenz, Humans, Female

040711
MoOrB1084