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Aggressive HAART + IL-2 Is Unable to Induce HIV Remission in Early-Stage Disease after 18 Months A. LAFEUILLADE*, C. POGGI, L. CHOLLET, L. BEAUVAIS, P. NGO VAN, E. DOHIN, G. HITINGER, S. CHADAPAUD, S. CARRENO, and N. PROFIZI.
Gen. Hosp., Toulon; Glaxo Wellcome; BMS; Produits Roche, France Objective: Recent studies have suggested that combining HAART + IL-2 could lead potentially infectious HIV below detectable levels, raising the possibility of viral "remission" after stopping therapy. To test this hypothesis, we have measured the effects in different compartments of a 5-drug combination + 3 courses of IL-2 and 2 courses of g-interferon (to "purge" latent reservoirs, respectively lymphocytes and macrophages) in 10 HIV-1 naive patients during 18 months (M).
Methods: Zidovudine, ddI, 3TC, Saquinavir (600 mg BID), and Ritonavir (400 mg BID) were administered for 18 months. Plasma, PBL and lymph node cells (LNMC) were analysed sequentially for HIV RNA, HIV DNA, and lymphocyte subsets. A coculture of isolated CD4+ PBL in enhanced conditions was performed at M 18. Two patients stopped therapy at M18.
Results: At baseline, plasma RNA was 4.46±0.18 log copies/ml; LNMC RNA was 5.26±0.19 log copies/106 cells, proviral DNA was 3.25±0.11 copies/106 PBL, CD4+ T cells were 24±6%. Plasma RNA dropped <20 copies/ml in each case. A transient rise in plasma RNA was observed following IL-2 or g-Interferon administration. LNMC RNA was 2.71±0.35 at M3, 2.03±0.30 at M6, 1.76±0.41 at M12 and 2.01 ±0.74 log copies/106 cells at M18. Proviral DNA decrease in PBL began at M3 (-0.7 log) and was -0.83 log at M9 and -0.85 log at M12. Coculture of CD4+CD45RO+ PBL was positive for HIV in all cases at M18. Two patients who stopped therapy at M18 had a rapid rebound in plasma RNA, about 1 log higher than it was at baseline.
Conclusion: At least with this design, combining HAART + cytokines is not enough to induce viral remission (i.e. to stop HAART without rebound).
Key Words: HAART, interleukin-2, viral reservoirs
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