Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID-19: initial assessment

J Int AIDS Soc. 2020 Apr;23(4):e25489. doi: 10.1002/jia2.25489.

Abstract

Introduction: Several antiretroviral drugs are being considered for the treatment of COVID-19, the disease caused by a newly identified coronavirus, (SARS-CoV-2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials.

Methods: Three databases were screened from inception to 30 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS or COVID-19 treated with antiretrovirals.

Results: From an initial screen of 433 titles, two randomized trials and 24 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 21 observational studies reporting treatment outcomes, there were three studies among patients with SARS, six studies among patients with MERS and 12 studies among patients with COVID-19. In one randomized trial 99 patients with severe COVID-19 illness were randomized to receive LPV/r (400/100 mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100), but this difference was not statistically significant. The second trial found no benefit. The certainty of the evidence for the randomized trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post-exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size.

Conclusions: On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID-19.

Keywords: COVID-19; HIV; MERS; SARS; antiretroviral therapy; coronavirus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • Betacoronavirus
  • COVID-19
  • Coronavirus / drug effects*
  • Coronavirus / isolation & purification
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Drug Combinations
  • Female
  • Humans
  • Lopinavir
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Ritonavir
  • SARS Virus / drug effects
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / drug therapy
  • Severe Acute Respiratory Syndrome / epidemiology

Substances

  • Anti-Retroviral Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Ritonavir

Supplementary concepts

  • COVID-19 drug treatment