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Abstract
A PILOT STUDY OF SHORT CYCLE INTERMITTENT ARV THERAPY UTILIZING A ONCE PER DAY REGIMEN OF DIDANOSINE, LAMIVUDINE AND EFAVIRENZ
By: M. Dybul1, E. Nies-Kraske1, R. Dewar2, F. Maldarelli3, S. Piscitelli4, C. Hallahan1, M. Daucher1, L. Ehler1, J. Metcalf1, R. Davey1, D. Rock Kress1, A. Powers1, I. Beck5, L. Frenkel5, M. Baseler2, A. Fauci1
1Lab. of Immunoregulation, NIAID/NIH/DHHS, Bethesda, USA, 2SAIC, Rockville, USA, 3NCI/NIH/DHHS, Bethesda, USA, 4Tibotec-Virco, Mechelen, Belgium, 5Univ of Washington and Children’s Hospital, Seattle, USA
Background: We have previously demonstrated that short cycle intermittent therapy (SIT) with a dual PI-based regimen maintained suppression of plasma HIV RNA and preserved CD4+ T cell counts while reducing serum lipid levels. However, strict adherence to such a regimen is problematic in certain patients. A once per day regimen may improve adherence.
Methods: 8 patients with plasma HIV RNA <50 c/ml for > 6 months and a CD4+ T cell count >300 cells/mm3 received ddI, 3TC and EFV in cycles of 7 days on followed by 7 days off ARV. All patients were receiving an EFV-based regimen prior to enrollment.
Results: 7 patients remain on study for 52 to 72 weeks with plasma HIV RNA <50 c/ml at every monthly measurement; all values are after the off-ARV period. 1 patient withdrew at week 24 with plasma HIV RNA <50 c/ml. The mean CD4+ T cell count at baseline (BL) of 701 cells/mm3 (323-1014) was not different than the mean count of 721 cells/mm3 (425-1053) at week 48 (p>0.5). Although there was no significant reduction in serum lipid levels from BL to week 48, 2/2 patients with high BL total cholesterol levels had substantial reductions at week 48 (265 to 204 and 244 to 186) and 4/4 patients with high BL triglyceride levels had a mean reduction of 19% at week 48. There was no difference in serum ALT or AST from baseline to week 48; however, BL values were 31 and 27 IU/L, respectively. The mean plasma level of EFV following a 7 day period off-ARV was 275 ng/ml (73-718). There was no evidence for the emergence of genotypic resistance to ARV at week 48.
Conclusions: A once per day regimen of short cycle SIT (7 days on followed by 7 days off ARV) maintained suppression of plasma HIV RNA for 48 to 68 weeks in a pilot study of 7 individuals. The lack of a single ‘blip’ in plasma viremia may indicate that the prolonged half-life of EFV is advantageous in short cycle SIT strategies in which viral rebound is not expected. The lack of a significant reduction in markers of toxicity may be due to the relatively low BL levels of these markers in patients receiving an EFV-based regimen at enrollment. A once per day short cycle SIT regimen may be an important strategy to reduce ARV exposure by 50%. This may have particular relevance for resource-limited settings and for the potential use of directly observed therapy.
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