445   Viral Resistance Results from the International, Multicenter, Randomized, Placebo-Controlled, 48-Week Study of Hydroxyurea (HU) or Placebo Combined with Efavirenz (EFV), Didanosine (ddl) and Stavudine (d4T) in Treatment-Naive and - Experienced Patients.

V. Johnson*¹, C. Delaugerre², J. Hazelwood¹, B. Berzins³, E. Belsey⁴, R. Rhodes¹, V. Calvez², C. Katlama², and R. Murphy³for the Intl. 3d Study Team.
¹Univ. of Alabama at Birmingham;²Pitie-Salpetriere Hosp., Paris, France;³Northwestern Univ., Chicago, IL; and⁴SigmaPlus Intl., Naples, FL.

Background:Pts were CD4⁺>100 c/mm³

plasma HIV RNA >500 c/ml, and therapy naïve (n = 98) or experienced (n = 47) (no prior HU or NNRTIs, HIV RNA <100,000 c/ml, <12 weeks ddI and/or d4T). To date, treatment-naïve pts had HIV RNA <50 c/ml at wk 24 in 87% with no benefit of additional HU. There was a trend toward improved activity in treatment-experienced pts with EFV/ddI/d4T/HU (80% vs 57% for HIV RNA <50 c/ml at wk 24).

Methods:Sequencing of plasma RT and PR was performed using the TruGene assay (Visible Genetics) (UAB) or PE ABI 377 (France). Confirmed treatment failures had HIV RNA >500 c/ml at 2 separate visits on therapy.

Results:In treatment-naïve pts, treatment failure was seen in only 4 (1 HU/3 placebo [P]), 2 with BL HIV RNA >100,000 c/ml. In 3 available specimen pairs (P): wk 0 RT mutations—none; at failure wks 32—48: RT 103N (1), 103N + 108I (1), 190S + 215F (1). Sequences were obtained from 39 of 41 available treatment-experienced baseline (BL) pt specimens (17 HU/22 placebo). There was evidence of 1 or more NRTI resistance-conferring mutations in 35/39: RT 41L (8), 62A/V (1), 67N (6), 69D (2), 70R (5), 75M (1), 184V (34), 210W (3), 215Y/F (8), 219Q (1),>2 TAMs (10), 69 insert or 151M (0). In pts with prior treatment, only 8 treatment failures were seen at wks 24—48 (3 HU/5 P). All 3 on HU had prior ZDV/3TC/NLF, whereas 4 of 5 on P had only 2—4 prior NRTIs. At wk 0 (n = 8 sequences): RT 41L (1), 103K/R (1), 184V (6), 215F (1); at failure wks 24—48 (n = 7) new RT 70K/R (1), 103N (7), 108I (1), 190A (1); 3 lost predominant 184V.

Conclusions:There was evidence of>1 NRTI-associated RT mutation in most viruses from therapy-experienced pts at study entry. In therapy-naïve and experienced pts, the mechanism of treatment failure at wks 24—48 included emergence of NNRTI mutations. The addition of HU to combined EFV/ddI/d4T therapy in therapy- experienced subjects at study entry did not prevent the emergence of the EFV-associated RT K103N mutation