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JAIDS Journal of Acquired Immune Deficiency Syndromes:
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Pilot Study of a Combination of Highly Active Antiretroviral Therapy and Cytokines to Induce HIV-1 Remission.

Lafeuillade, Alain; Poggi, Cécile; Chadapaud, Stéphane; Hittinger, Gilles; Chouraqui, Martine; Pisapia, Magali; Delbeke, Emmanuel

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Abstract

Summary: A pilot study of a combination of highly active antiretroviral therapy (HAART) and cytokines in early HIV-1 infection has been undertaken to test the hypothesis that HIV-1 remission can be reached with this strategy by flushing latently infected viral reservoirs. Ten previously antiretroviral naive patients have received a combination of zidovudine, lamivudine, didanosine, saquinavir, and ritonavir for 72 weeks. Between weeks 12 and 48, three courses of interleukin (IL)-2 (7.5 millions of international units [MUI] twice a day for 5 consecutive days) and 2 courses of [gamma]-interferon (IFN) (100 [mu]g every other day during 2 weeks) were administered subcutaneously. All patients reached plasma HIV-1 RNA levels < 20 copies/ml within 12 +/- 4 weeks. Transient increases in plasma levels (<120 copies/ml) were observed during administration of IL-2, but less frequently during [gamma]-IFN administration. HIV-1 RNA decreased in lymph node cells by ~ 4 log, then remained stable after week 24. A mean drop of -0.8 log in peripheral blood mononuclear cell (PBMC) proviral DNA was observed during the trial. Isolation of potentially infectious HIV-1 was successful in each case by coculture of CD4+ T cells taken at week 72. The 2 patients who stopped therapy at the end of the trial showed rebounding plasma HIV-1 RNA levels within a few weeks. No additional mutations were selected in comparison with those present at baseline in 8 patients. In addition, 2 patients developed new mutations in the reverse transcriptase or protease gene and in 1 case, resistance selection was found in lymphoid tissue HIV-1 RNA but not in latently infected cells. In all cases, a rapid increase in both naive and memory CD4+ T cells was observed, with a reduction in activation markers and preservation of the CD8+CD28+ subset. Consequently, an aggressive regimen of HAART and cytokines administered in early stage disease is associated with a positive effect in terms of proviral load reduction and immune reconstitution but is unable to induce HIV-1 remission, allowing low levels of viral replication to persist in lymphoid reservoirs.

(C) 2001 Lippincott Williams & Wilkins, Inc.

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