Risk of viral failure after simplification therapy without using integrase inhibitors compared with maintenance of triple antiretroviral therapy: A systematic review and meta-analysis

Braz J Infect Dis. 2024 Nov-Dec;28(6):104463. doi: 10.1016/j.bjid.2024.104463. Epub 2024 Nov 17.

Abstract

Background: Antiretroviral drug simplification is a strategy to reduce drug exposure and improve treatment adherence. Nowadays, dolutegravir plus lamivudine is the most preferred regimen, which might lead in the future with problems related to drug resistance or drug intolerance. This meta-analysis aimed to assess the safety of HAART simplification without integrase inhibitors.

Methods: We conducted a systematic review and meta-analysis using the Embase and Medline databases to include clinical trials and observational studies published between 2008 and March 2024. The studies focused on HIV-positive individuals with suppressed viral load who either simplified their treatment to dual therapy without integrase inhibitors or continued triple therapy. The primary outcome of interest was the likelihood of viral failure within 48 weeks.

Results: Ten studies were included, with a total of 1,977 patients. Boosted Protease Inhibitors (PI) were the core of antiretroviral simplification therapy. The simplification group did not show an increased risk of virological failure, with a pooled RR in 48 weeks of 1.29 (0.61‒2.73, I² = 51 %) when compared to control group. Boosted protease inhibitors were preferred combined with lamivudine, nevirapine, efavirenz, and maraviroc). Only maraviroc plus boosted PI combination was associated with a higher risk of virological failure with an RR of 4.49 (1.99‒10.11).

Conclusion: Simplification therapy with boosted PI plus lamivudine or non-nucleoside transcriptase reverse inhibitors was a safe strategy and not associated with a higher risk of virological failure. This approach might be an alternative to dolutegravir-based simplification regimens if needed.

Keywords: Aids; Boosted protease inhibitor; Dual therapy; Haart; Hiv; Simplification; Virological failure.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • Drug Therapy, Combination
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV Integrase Inhibitors* / therapeutic use
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Lamivudine / therapeutic use
  • Oxazines
  • Piperazines
  • Pyridones
  • Risk Factors
  • Treatment Failure
  • Viral Load* / drug effects

Substances

  • HIV Integrase Inhibitors
  • Lamivudine
  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • dolutegravir
  • Oxazines
  • Piperazines
  • Pyridones