Barreiro P, Camino N, de Mendoza C, Soriano V, Blanco F, Valencia E, Gonzalez-Lahoz J; Conference on Retroviruses and Opportunistic Infections.
9th Conf Retrovir Oppor Infect Feb 24 28 2002 Wash State Conv Trade Cent Seattle Wash Conf Retrovir Oppor Infect 9th 2002 Seattle Wash. 2002 Feb 24-28; 9: abstract no. 533-M.
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/micro-L in subsequent 3-month visits. Percentages and mean values were compared using X(2) 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/micro-L, 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/micro-L (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.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antiretroviral Therapy, Highly Active
- CD4 Lymphocyte Count
- Didanosine
- Drug Therapy, Combination
- HIV Infections
- Hemolytic-Uremic Syndrome
- Humans
- Male
- Viremia
- drug therapy
- therapy
- virology
Other ID:
UI: 102263729
From Meeting Abstracts