AEGiS-14IAC: Strategies to prevent loss of CD4 and onset of resistance during treatment interruptions.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Strategies to prevent loss of CD4 and onset of resistance during treatment interruptions.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeB9025)

Lori F, Maserati R, Foli A, Tomasoni L, Migliorino M, Maggiolo F, Pan A, Paolucci S, Tinelli C, D'Aquila R, Lisziewicz J
RIGHT at Policlinico S. Matteo, Pavia and Washington DC, Pavia, Italy

BACKGROUND: Pilot, uncontrolled studies in chronically infected patients suggested that STI cause the loss of CD4 T cells and the onset of drug resistance. Maintaining CD4 counts and resistance profiles similar to those seen during continuous HAART would represent a significant improvement of STI.

METHODS: RIGHT 901 randomized 60 drug-naïve patients with chronic HIV infection (CD4>250, VL >5000) in a 2 x 2 factorial design to receive ddI-d4T-IDV or ddI-d4T-HU for 12 weeks, then 24 weeks of STI (3 weeks on/3 weeks off therapy, for 4 cycles) or continuous HAART. Therapy was stopped in all groups at week 36. Nonparametric tests were used for statistical analysis.

RESULTS: The rate of VL rebound decreased from 0.13 log/day to 0.08 log/day, and the rate of VL suppression after therapy restart did not change during STI. The proportion of patients with VL rebound >10000 c/ml at week 39 was similar regardless of previous schedule (HAART, 88%; STI, 87.5%; p=0.6), and regimens (HU, 88.5%; IDV, 90%; p=0.6). Despite VL rebounds, IDV-STI treated patients had a median CD4 increase from baseline to week 36 similar to IDV-HAART (+92 and +118 cells/ml, respectively, p=0.45). Surprisingly, unlike HU-HAART treated patients (-5 cells/ml CD4), those on HU-STI not only experienced a significant (p=0.002) CD4 increase (+110 cells/ml), but were also exempt from the brisk fall of CD4 counts during treatment interruptions typical of IDV-STI patients. Even in the presence of mutations at baseline predisposing resistance to IDV, no genotypic change was observed during STI. A relevant mutation in the RT sequence (K70R) emerged in one patient treated with continuous HAART. Side effects (no major events) were similar among groups.

CONCLUSIONS: Rates of VL suppression, CD4 increase, and onset of resistance comparable to continuous HAART might be obtained during STI through the choice of drugs less prone to resistance and/or able to prevent CD4 fluctuation.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Antigens, CD4, Didanosine, Stavudine, Acquired Immunodeficiency Syndrome, Drug Therapy, Combination, Human, therapy, immunology, drug therapy

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LbPeB9025