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Influence of Interleukin-2 (IL-2) on Productive and Latent HIV Infection and on Viral Rebound H. J. STELLBRINK*1, J. VAN LUNZEN1, M. WESTBY6, E. O’SULLIVAN6, N. CAMMACK6, A. ADAM1, L. WEITNER1, B. KUHLMANN2, C. HOFFMANN4, H. HORST4, S. FENSKE1, G. SCHMIDT-HARTNACK1, S. P. ARIES3, K. DALHOFF3, C. SCHNEIDER1, O. DEGEN1, F. T. HUFERT5, K. TENNER-RACZ1, and P. RACZ1.
Univ. Hosp. Eppendorf, Bernhard Nocht Inst. 1Hamburg, 2Hannover, 3Lübeck, 4Kiel, and 5Freiburg, Germany; and 6Roche Welwyn, UK Objective: To assess if IL-2 has a direct or indirect antiviral effect in vivo
Methods: Open, randomized comparison of quadruple-drug HAART vs. HAART + IL-2 in 56 patients with >350/mm³ CD4+ T cells or recent seroconversion. Plasma viremia and T-cell subsets were determined at days 0,14,28, and monthly, after Tx discontinuation at weeks 1,2,4, and 8. Lymph node (LN) biopsies obtained before Tx and after >6 mths of neg. ultrasensitive RNA PCR were examined by in-situ hybridisation (n=31). 120 HIV-neg. controls were used to establish age- and gender-adjusted normal values for lymphocyte subsets.
Results: Baseline: age 41, CD4+ 410, CD8+ 878 (/mm³), CD4+:CD8+ ratio: 0.47, HIV RNA 4.83 log10, mean f/u: 572 days. There was no difference in the magnitude or kinetics of plasma viremia decrease. IL-2 achieved a higher rate of normalisation of CD4+ T cell counts, persisting after the end of IL-2 administration. Virus production was still detected in follow-up LN biopsies of 10/16 IL-2 and 11/15 non-IL-2 patients (35-40 cutting levels). Levels of proviral DNA and kinetics of decrease showed no significant difference between both groups. After Tx discontinuation, HIV RNA rebounded with very rapid kinetics and to transiently higher levels than at baseline. One IL-2 patient subsequently cleared viremia in the absence of therapy.
Conclusions: Despite a strong and durable immunomodulatory effect, IL-2 has no persistent effect on virus production or latent infection in vivo and the immunological control over HIV infection.
Key Words: Interleukin-2, latency, lymph node
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