533-M.
|
Maintenance Therapy with HU-ddI after Complete Viral Suppression on HAART: Results at 48 Weeks
P. Barreiro*, N. Camino, C. de Mendoza, V. Soriano, F. Blanco, E. Valencia, and J. Gonzalez-Lahoz
Hosp. Carlos III, Madrid, Spain
|
Background: HAART improves life expectancy of HIV+ patients, although adherence and toxicity are major concerns. HU-ddI is a simple regimen (3 pills daily), which combines a cytostatic effect (HU limits HIV target cell availability) and antiviral potency (HU enhances ddI activity).
Methods: All subjects with VL<50 copies/mL and CD4>350 copies/muL on HAART for >1 year, were randomized (1:1) in 1999 to switch to HU (500 mg BID) plus ddI (400 mg OD), or continue the same regimen. HAART was resumed in subjects on HU-ddI if VL>5000 copies/mL or CD4<200 copies/muL in subsequent 3-month visits. Percentages and mean values were compared using X2 and Student's t-tests.
Results: 223 subjects were randomized: 116 switched to HU-ddI, and 107 continued on HAART. Baseline characteristics were similar (age 38, 75% male, 71% ddI-experienced). In an ITT (M=F) analysis at 48 weeks, 45/116 (39%) and 41/107 (38%) subjects had VL<500 copies/mL in HU-ddI and control groups, respectively. Success on HU-ddI was related to lack of ddI experience (28% vs 7%, p<0.02), shorter time on antiretroviral therapy (60 vs 75 months, p<0.05), higher CD4 nadir (475 vs 336 copies/muL, p<0.01) and pre-HAART VL<100,000 copies/mL (93% vs 65%, p<0.02). Overall, median VL moved from 13,665 to 135 copies/mL comparing time pre-HAART and 48 weeks under HU-ddI (p<0.01). Mean CD4 count declined from 827 to 591 copies/muL (p<0.05) in the HU-ddI arm, with no variation in the control arm. Incidence of hyperChol/hyperTg moved from 71%/38% to 44%/28% (p<0.05), and partial reversion of LD features occurred in 70% of cases, after 48 weeks on HU-ddI; no variation was observed in the control group. Adverse reactions and poor adherence occurred more frequently in the HAART group: 38% vs 7%, and 11% vs 1%, respectively (p<0.01). ddI-resistant genotypes were detected in 35% (M184V and/or Q151M, and L74V) of subjects failing HU-ddI, and in 50% (L74V and M184V) of those with sustained virological success.
Conclusions: HU-ddI may be a satisfactory maintenance therapy in patients with good response to HAART. Viral fitness reduction associated with L74V mutation could contribute to sustain low levels of viremia. HU-ddI is better tolerated and easier to follow than HAART; moreover, lipodystrophy and lipid alterations revert in most subjects.
|
