Abstract 288 - Prolonged HAART Initiated within 120 Days of Primary HIV-1 Infection Does Not Result in Sustained Control of HIV-1 after Cessation of Therapy.

288 Prolonged HAART Initiated within 120 Days of Primary HIV-1 Infection Does Not Result in Sustained Control of HIV-1 after Cessation of Therapy.

M. Markowitz*, X. Jin, B. Ramratnam, M. Louie, R. Kost, A. Hurley, S. Barsoum, G. Deschenes, C. Chung, A. Kim, T. He, L. Zhang, and D. D. Ho.
Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY.

Background and Methods:In 1995 we initiated a program to assess the impact of HAART started during or shortly after primary HIV-1 infection. 14 subjects treated on average 60 days (range 7—120) after the onset of symptoms of acute HIV-1 infection elected to discontinue therapy after a mean of 1145 days (range 931—1822).

Results:Median pre-treatment values included plasma viral load of 4.6 log (range 3.8—6.8) and CD4 count of 522 cells/mm³(range: 227—954). All had less than one episode of detectable viremia per year during HAART. At the time of treatment discontinuation, plasma HIV-1 RNA levels were undetectable (<50 copies/ml) in all except one intermittently non-adherent subject, and the median CD4 count was 811 cells/mm³(range 422— 1306). Immune studies performed on the day of discontinuation, or within 7 days prior, revealed that 7 of 14 had CD4 proliferative responses (SI >5) to Gag and 10 of 14 had HIV-1-specific CTL as measured by the number of CD8⁺T-cells expressing IFN-gdetermined by FACS after exposure to vaccinia virus expressing Env, Gag, Pol, or Pol-Nef. All 14 experienced virologic rebound after a mean of 20 days (range 6—107) off therapy. Peak viremia was reached within 39 days (range 19—255) on average to a median value of 4.7 log (range 2.9—5.5). All subjects but one appeared to spontaneously lower the level of plasma viremia and was associated with a measurable increase in virus-specific cellular immune responses. However, after a median follow-up of 258 days (range 49— 630) off therapy, plasma viremia remained detectable between 2.9 and 4.2 log, together with a mean fall in CD4 cell counts of 297 cells/mm³(range -462 to +205). Only two patients had plasma viremia levels <1000 copies/ml while off therapy. Seven subjects elected to reinitiate HAART.

Conclusions:Early initiation of PI-containing HAART for 2.5 to 5 years does not result in sustained control of HIV-1 in the majority of subjects who discontinue therapy. These results call for more effective measures to reduce viral burden and augment HIV-1-specific immunity before discontinuing antiretroviral treatment.