Integrase Strand Transfer Inhibitors and the Emergence of Immune Reconstitution Inflammatory Syndrome (IRIS)

Curr HIV Res. 2017;15(6):405-410. doi: 10.2174/1570162X15666171122155708.

Abstract

Background: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting highly active anti-retroviral therapy (HAART) in new patients and especially late presenters. This study attempts to identify risk factors for IRIS and investigate whether certain treatment regimens increase the probability of IRIS for patients at risk.

Methods: Retrospective single-centre study of HIV patients treated with HAART.

Results: A total of 417 patients were included. We identified 45 cases of IRIS in 37 patients; an incidence of 13.3 cases over 1000 person-years. In univariate analysis, IRIS development was significantly associated with CDC stage, the presence of an opportunistic infection (OI) at diagnosis, CD4 cell count and viral load at diagnosis and HAART initiation and the use of integrase strand inhibitors (INSTIs). In multivariate analysis, INSTIs use (OR 2.89; 95%CI 1.26-6.64; p=0.012), CD4≤200/mm3 (OR 5.56; 95%CI 2.2-13.98; p<0.001), and the presence of an OI (OR 4.74; 95%CI 2.13-10.23; p=0.012) were independent risk factors. Among INSTI regimens, dolutegravir (OR 4.99 vs. NNRTI; 95%CI 1.11-22.55; p=0.037) and elvitegravir (OR 4.82 vs. NNRTI; 95%CI 1.43-16.19; p=0.011) seem to carry increased risk. Mortality was 18.9% (7/37) for IRIS patients compared to 9.7% (37/380) in the non-IRIS group. Mortality at any given time during follow-up was significantly higher in the IRIS group (HR 3.2; 95%CI 1.39-7.36; p=0.006).

Conclusion: The use of INSTIs and especially DTG and EVG is associated with a higher probability for the development of IRIS in the background of late presentation and the presence of OIs. These data highlight the need for further research.

Keywords: HAART; HIV; immune reconstitution inflammatory syndrome; integrase strand transfer inhibitors; late presenters.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Comorbidity
  • Disease Susceptibility*
  • Female
  • Follow-Up Studies
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology*
  • HIV Infections / virology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / diagnosis
  • Immune Reconstitution Inflammatory Syndrome / epidemiology*
  • Immune Reconstitution Inflammatory Syndrome / etiology*
  • Male
  • Middle Aged
  • Mortality
  • Odds Ratio
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Risk Assessment
  • Risk Factors
  • Young Adult

Substances

  • Reverse Transcriptase Inhibitors