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Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial)

2002; Lippincott Williams & Wilkins; Volume: 16; Issue: 11 Linguagem: Inglês

10.1097/00002030-200207260-00004

1473-5571

Hans‐Jürgen Stellbrink, Jan van Lunzen, Michael Westby, Eithne O’Sullivan, Claus Schneider, Axel Adam, Lutwin Weitner, Birger Kuhlmann, Christian Hoffmann, Stefan Fenske, Philipp S. Aries, Olaf Degen, Christian Eggers, H. Petersen, Friedrich Haag, Heinz A. Horst, K. Dalhoff, Christiane Möcklinghoff, Nick Cammack, Klara Tenner‐Racz, Paul Rácz,

HIV/AIDS Research and Interventions

Background The effect of interleukin-2 (IL-2) in combination with antiretroviral therapy on HIV-1 replication and reservoirs was investigated. Methods In a prospective, open-label trial, 56 asymptomatic HIV-1-infected subjects (CD4 T cell count > 350 × 106 cells/l) were randomized to highly active antiretroviral therapy (HAART: stavudine, lamivudine, nelfinavir, saquinavir) with or without IL-2 (9 megaunits daily for 5 days in 6-weekly intervals for a total of eight cycles). Productive and latent infection were analysed in peripheral blood, and residual virus replication in the lymphoid tissue and in the cerebrospinal fluid. The influence of IL-2 on viral rebound after treatment discontinuation was studied. Results Virus replication was detected in 21 of 31 on-treatment lymph nodes despite undetectable plasma viraemia. Viral RNA was found in resting as well as in proliferating cells. RNA-negative patients tended towards more rapid proviral DNA elimination. Supplementary IL-2 led to a greater increase in CD4 T cell counts than HAART alone (P < 0.001), resulting in normalization in ~90% of IL-2-treated patients compared with ~50% HAART-only subjects. IL-2 had no beneficial effect on virus replication and on proviral DNA in peripheral blood. Conclusions Viral persistence during HAART is partly a result of continued low-level replication, calling for more active regimens. IL-2 accelerates the normalization of CD4 T cell counts but does not impact on virus production or latency.