Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death

AIDS. 2011 Feb 20;25(4):441-51. doi: 10.1097/QAD.0b013e3283430013.

Abstract

Background: A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.

Methods: Immunological and clinical endpoints were evaluated in 2491 participants of the Swiss HIV Cohort Study initiating ART during a mean follow-up of 7.1 years. Data were analysed in persons with treatment interruptions (n = 1271; group A), continuous ART, but intermittent HIV-1 RNA at least 1000 copies/ml (n = 469; group B) and continuous ART and HIV-1 RNA constantly less than 1000 copies/ml (n = 751; group C). Risk factors for low CD4 T-cell counts and clinical events were analysed using Cox proportional hazards models.

Results: In groups A-C, CD4 T lymphocytes increased to a median of 427, 525 and 645 cells/μl at 8 years. In group A, 63.0 and 37.2% reached above 350 and 500 CD4 T cells/μl, whereas in group B 76.3 and 55.8% and in group C 87.3 and 68.0% reached these thresholds (P < 0.001). CD4 T-cell recovery directly depended on the cumulative duration of treatment interruptions. In addition, participants of group A had more Centers for Disease Control and Prevention B/C events, resulting in an increased risk of death. Major risk factors for not reaching CD4 T cells above 500 cells/μl included lower baseline CD4 T-cell count, higher age and hepatitis C virus co-infection.

Conclusion: In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed. CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • AIDS-Related Opportunistic Infections / prevention & control*
  • Adult
  • Anti-Retroviral Agents / administration & dosage*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / mortality
  • HIV-1 / immunology*
  • Humans
  • Male
  • Risk Factors
  • Time
  • Viral Load
  • Withholding Treatment*

Substances

  • Anti-Retroviral Agents