502   Antiretroviral Intensification Accelerates the Decay of the Latent Reservoir of HIV-1 and Decreases but Does Not Eliminate Ongoing Virus Replication.

B. Ramratnam*¹, R. Ribeiro², T. He¹, P. Cauldwell³, N. Ruiz⁴, A. Hurley¹, L. Zhang¹, A. S. Perelson², D. D. Ho¹, and M. Markowitz¹.
¹Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY;²Los Alamos Natl. Lab., NM;³Glaxo Wellcome, Inc., Res. Triangle Park, NC; and⁴Dupont Pharmaceutical Co., DE.

Background:The pathogenesis of ongoing viral replication during HAART is unclear.

Methods:To address this issue, a treatment intensification study was conducted. ABV with or without EFV was added to the regimen of individuals receiving AZT/3TC plus NLV or RIT/SAQ. The rate of decay of the HIV-1 latent reservoir and the frequency of intermittent viremia were compared between 5 patients who underwent intensification and 5 control subjects with comparable baseline characteristics. ABV (n = 4) or ABV/EFV (n = 1) was added after a mean of 34 mos. of treatment. Mean duration of intensification was 14 mos.

Results:There was no statistically significant difference in median frequency of intermittent viremia/yr. between the two groups (3.3/yr. vs. 2.8/yr., p = 0.531) prior to intensification. A significant inverse correlation was found between the frequency of intermittent viremia and the slope of decay of the latent reservoir (p = 0.004). When compared to control patients, median t_1/2of the latent reservoir decreased from 31 to 10 mos (p = 0.016) after intensification. The frequency of intermittent viremia/yr also decreased in 4/5 individuals following intensification (2.4/yr. vs. 0.8/yr.).

Conclusions:Based on these data, it would appear that ongoing virus replication during HAART is due, in part, to the inadequate antiviral potency of current regimens. Although treatment intensification yielded detectable improvements in antiviral potency, HIV-1 replication was not completely suppressed.