A pilot study evaluating time to CD4 T-cell count <350 cells/mm 3 after treatment interruption following antiretroviral therapy ± interleukin 2: Results of ACTG A5102

Keith Henry, David Katzenstein, Deborah Weng Cherng, Hernan Valdez, William Powderly, Michelle Blanchard Vargas, Nasreen C. Jahed, Jeffrey M. Jacobson, Laurie S. Myers, John L. Schmitz, Mark Winters, Pablo Tebas

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25 Scopus citations

Abstract

BACKGROUND: Although an intermittent antiviral treatment (ART) strategy may limit long-term toxicity and cost, there is concern about the risk for virologic failure, selection of drug resistance mutations, and disease progression. By boosting CD4 T-cell counts, interleukin 2 (IL-2) could safely prolong the duration of treatment interruption (TI) in a CD4-driven strategy. METHODS: The AIDS Clinical Trials Group (ACTG) study A5102 evaluated 3 cycles of IL-2 before TI, on clinical and immunologic outcomes, using a CD4 T-cell count of <350 cells/mm as the threshold for restarting ART. Forty-seven HIV-infected subjects on potent ART with CD4 T-cell counts of ≥500 cells/mm or more and HIV RNA levels of less than 200 copies/mL were randomized to arm A (ART + three 5-day cycles of IL-2 at 4.5 million U, Sc, BID every 8 weeks, n ≤ 23) or arm B (ART alone, n ≤ 24) for 18 weeks (step 1). At the end of step 1, subjects with a CD4 T-cell count of ≥500 cells/mm or more stopped ART until a CD4 count of <350 cells/mm (step 2). CD4 T-cell count, time to return of viremia, and the emergence of drug resistance mutations after TI were compared between study arms. RESULTS: IL-2 recipients maintained higher CD4 counts during TI for 48 weeks with a waning of the CD4 effect by 72 weeks. A sustained CD4 T-cell count of more than 350 cells/mm and more durable TI were associated with a higher nadir CD4 T-cell count before ART and higher naive CD4 T-cell count at entry. After TI, a higher viral set point and drug resistance mutations at virologic rebound were associated with a shorter time to CD4 T-cell count of less than 350 cell/mm. There were no differences in the magnitude of virologic rebound (at week 8 of step 2, median log10 HIV RNA level was 4.23 for arm A and 4.21 for arm B) or the steady-state HIV-1 RNA level after week 8. CONCLUSIONS: IL-2 before TI did not prolong time to CD4 of less than 350 cells/mm. A TI strategy utilizing a CD4 T-cell threshold of less than 350 cells/mm for restarting ART appears generally safe with most subjects in both arms remaining off ART for more than 1 year. Implications of our results for TI strategies include the potential advantage of starting ART at higher CD4 T-cell levels while avoiding any drug resistance and evaluating immunomodulators or drugs to reduce T-cell activation and HIV-1 RNA rebound during the TI.

Original languageEnglish (US)
Pages (from-to)140-148
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume42
Issue number2
DOIs
StatePublished - Jun 1 2006

Keywords

  • ACTG A5102
  • Antiretroviral therapy
  • Interleukin 2

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