Late Breaker Session 11
Structured Cyclic Antiretroviral Therapy Interruption in Chronic Infection May Induce Immune Responses Against HIV-1 Antigens Associated with Spontaneous Drop in Viral Load

• LB11: Structured Cyclic Antiretroviral Therapy Interruption (STI) in Chronic Infection May Induce Immune Responses Against HIV-1 Antigens Associated with Spontaneous Drop in Viral Load (Authored by F. Garcia, M. Plana, G.M. Ortiz, A. Soriano, C. Vidal, A. Cruceta, M. Arnedo, G. Pantaleo, T. Pumarola, T. Gallart, D.F. Nixon, J.M. Miro, and J.M. Gatell. Hosp. Clin., Barcelona, Spain; Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY; and Univ. of Lausanne, Switzerland)
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In contrast to the previous report, which studied drug holidays in people with high viral loads, this study investigated the dynamics of viral load rebound and HIV-1 specific immune responses after three consecutive cycles of drug interruption, or STI, in people with good virologic suppression, or HIV RNA less than 20 copies, on their current treatment regimen.

Ten HIV-infected people, treated with d4T, 3TC and ritonavir or indinavir for 52 weeks, and HIV RNA less than 20 copies more than 32 weeks, underwent three four-week cycles of STI (stopped their drugs), separated by six-month periods back on their drugs.

Immediately before discontinuing HAART at week 0, 28, and 56 (first, second, and third stop, respectively), plasma HIV RNA was less than 20 copies in all people in the study. A rebound in plasma viral load was detected in all cases, with an average HIV doubling time of 2.23, 3.38, and 3.25 days (first, second, and third stop, respectively). At the second stop, in four of the nine patients, HIV RNA initially rebounded to similar levels prior to HAART, but then dropped somewhat spontaneously thereafter. These four patients developed laboratory evidence of strong HIV-specific immune responses. After the first, second, and third stop, no mutations associated with resistance to reverse transcriptase or protease inhibitors were detected. After the third stop, a spontaneous drop in HIV RNA, and improvements in HIV-specific immune responses was detected in three out of seven evaluable patients. Also, the HIV RNA set-point, or the level at which the HIV RNA stabilized, was lower in four out of seven people after the third stop, compared to their pre-HAART viral load level. However, the CD4, or T-helper, cell counts, decreased after the third stop to the level they were prior to initially starting antiretroviral drugs.

In conclusion, these preliminary results from a very small number of people show that structured antiretroviral therapy interruption may induce effective immune responses against HIV-1 antigens in some people, which may result in a decrease in plasma HIV RNA levels. Whether these potential "benefits" of STI will offset the risk of a significant decrease in CD4 cell counts, and result in a net clinical benefit, remains to be determined by larger, ongoing studies, with longer follow up.

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