Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial

J Antimicrob Chemother. 2017 Mar 1;72(3):829-836. doi: 10.1093/jac/dkw462.

Abstract

Background: Initiating ART during acute/recent HIV-1 infection reduces viral reservoir formation. It has been proposed that, during this phase, the size of the viral reservoir could be further reduced by the association of immunomodulatory therapy with ART. Contradictory results have emerged, however, from two trials evaluating the impact on immune recovery and the viral reservoir of adding cyclosporine A to ART during primary HIV-1 infection.

Patients and methods: Twenty patients with acute/recent HIV-1 infection were randomized to receive ART alone (tenofovir, emtricitabine and lopinavir/ritonavir) or associated with 8 weeks of cyclosporine A (0.3-0.6 mg/kg twice daily). The impact on viral load, immune response and integrated and non-integrated DNA viral reservoir at 0, 8 and 36 weeks of treatment was evaluated.

Results: The estimated median time from HIV-1 infection to ART onset was 63 days (IQR 53; 79.5) with 90% of patients at Fiebig V stage. No significant differences were observed in viral load decay, CD4 T cell recovery, immune response markers or the evolution of integrated DNA at week 8 (end of cyclosporine A) and week 36 between groups. However, non-integrated DNA significantly increased in the cyclosporine A arm between weeks 0 and 36. Cyclosporine A was well tolerated.

Conclusions: Adding cyclosporine A to ART during acute/recent infection did not improve immune recovery. However, unintegrated DNA increased in the cyclosporine A group, suggesting an anti-integration effect, a point warranting further research (ClinicalTrials.gov Identifier: NCT00979706).

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • Cyclosporine / administration & dosage*
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • Humans
  • Lopinavir / administration & dosage
  • Lopinavir / therapeutic use
  • Male
  • Middle Aged
  • Pilot Projects
  • Ritonavir / administration & dosage
  • Ritonavir / therapeutic use
  • Young Adult

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Lopinavir
  • Cyclosporine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00979706