Continuous versus intermittent treatment strategies during primary HIV-1 infection: the randomized ANRS INTERPRIM Trial

AIDS. 2012 Sep 24;26(15):1895-905. doi: 10.1097/QAD.0b013e32835844d9.

Abstract

Objectives: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI).

Design and methods: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption.

Results: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups.

Conclusion: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / physiopathology
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacology
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / drug effects*
  • DNA, Viral / drug effects
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / pharmacology
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2b