AEGiS-13IAC: A randomized, controlled trial of intermittent versus continuous highly active antiretroviral therapy (HAART).

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

A randomized, controlled trial of intermittent versus continuous highly active antiretroviral therapy (HAART).

Int Conf AIDS 2000 Jul 9-14; 13:19 (abstract no.. LbOr11)

Dybul M, Yoder C, Belson M, Chun TW, Hallahan C, Justement JS, Hertogs K, Larder B, Metcalf J, Davey R, Fauci A;;; Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892. Fax: 301-402-0070, E-mail: mdybul@nih.gov.

BACKGROUND: Continuous HAART, although effective in many patients, can be toxic and prohibitive in cost for many countries, and adherence is difficult. By decreasing the time that patients receive medications, intermittent HAART could reduce cost and toxicity while enhancing adherence.

METHODS: 70 HIV-infected individuals with plasma HIV RNA < 500 copies/ml > 3 months and < 50 copies/ml at screening and a CD4+ T-cell count >300 cells/mm³ will be randomized to receive continuous HAART or cycles of 4 weeks off HAART followed by 8 weeks on HAART for 22 months. Preliminary results are discussed.

RESULTS: After 2-3 cycles, 3/4 patients had a decrease in plasma HIV RNA: mean log reduction of 0.9 (cycle 2) and 1.2 (cycle 3) compared to cycle 1. All patients returned to <50 copies/ml after the on-drug periods. There was a decrease in CD4+ T-cell counts (mean 32%) with cycle 1 that was less with cycle 2 (7%) and counts returned to baseline after the on-drug periods. While there was no increase in CD8+ T-cells, an increase in CD8CD38+ T-cells with cycle 1 (27%) was less with cycle 2 (14%). There was no increase in CD8+ T-cell intracellular IFN-gamma responses to HIV gag, pol, env or nef or in CD4+ T-cell proliferation to p24 antigen from cells obtained immediately before interruption (cycles 1 and 2). 2/3 Class I HLA-A2+ patients had increases in gag and pol positive CD8+ T-cells by tetramer analysis. Genotype and phenotype drug susceptibility assays and data from 5 additional patients will be available for presentation.

CONCLUSION: There was a significant decline in peak plasma HIV RNA after each of 2-3 cycles of intermittent HAART. Furthermore, there was a lesser decrease in CD4+ T-cells and increase in CD8+ and CD8+CD38+ T-cells with each cycle. These preliminary data indicate that intermittent HAART may be an effective long-term therapeutic approach to control plasma HIV levels and maintain CD4+ T-cells while reducing toxicity and cost and enhancing adherence.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, HIV Infections, Antigens, CD8, Antigens, CD4, Randomized Controlled Trials, T-Lymphocytes, Human, immunology, AIDS
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