| |
Protease Inhibitor Class-Sparing Maintenance Therapy with Abacavir (ABC) + Lamivudine (3TC) + Zidovudine (ZDV) in Patients with Long-Term Suppression of HIV-1 RNA M. OPRAVIL*1, S. YERLY2, A. LAZZARIN3, H. J. FURRER4, J. P. CHAVE5, P. VERNAZZA6, E. BERNASCONI7, M. BATTEGAY8, C. PYTHON9, L. PERRIN2, B. HIRSCHEL2, and the Swiss HIV Cohort Study.
Univ. Hosp. 1Zurich, 2Geneva, 4Bern, and 8Basel; Cantonal Hosp. 6St. Gallen and 7Lugano; 5Lausanne; 9GlaxoWellcome; Switzerland; and 3S. Raffaele Hosp., Milano, Italy. Objectives: To assess if switching successfully pre-treated patients from a protease inhibitor (PI)-containing HAART to a simple triple nucleoside analogue regimen provides similar virologic efficacy and reduces PI-associated adverse events.
Methods: Patients with plasma HIV-1 RNA <50 copies/mL for >6 months following PI-containing HAART and no codon 215 ZDV resistance mutation at baseline were randomized to either continue their current PI-containing regimen or switch to a simplified regimen of ABC (300 mg bid) + Combivir (150 mg 3TC + 300 mg ZDV bid). HIV-1 RNA was measured every 4 weeks. Virologic failure was defined as 2 consecutive HIV-1 RNA values >400 copies/mL.
Results: Of 164 randomized patients (129 males, mean age 45 years, mean duration of prior HAART 22 months, duration of suppressed HIV RNA 15.5 months), 80 are in the continuation and 84 in the simplified arm. After overall follow up of 121 patient-years (median 32 weeks), 4 and 7 virologic failures occurred in the continuation and the simplified arm, respectively (intent-to-treat analysis), despite >95% adherence. Among 3 break-through isolates on ABC/Combivir, 184 and 215 codon mutations were present in all 3, and 41 codon mutation in 2 of them. Resistance mutations in additional failing isolates are being examined. While the course of CD4 and CD8 lymphocytes did not show significant differences between the arms, decreases in cholesterol (p<0.05 weeks 12-48) and triglycerides (n.s. trend), and increase in HDL-cholesterol (p>0.05 weeks 24-36) occurred in the simplified arm.
Conclusions: These interim results suggest that the switch to a simple PI-sparing regimen with 3 nucleoside analogues is capable of providing comparable HIV suppression and of correcting lipid abnormalities in patients previously on PI-containing combination therapy.
Key Words: abacavir, hyperlipidemia, maintenance therapy
|
