Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA)

J Clin Virol. 2018 Aug:105:112-117. doi: 10.1016/j.jcv.2018.06.012. Epub 2018 Jun 21.

Abstract

Background: Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens.

Objectives: We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response.

Study design: From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression.

Results: After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001) and significantly decreased in patients with CD4 nadir >200/μL (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start.

Conclusions: After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.

Keywords: Dolutegravir; Drug resistance; Durability; Genotype; Human immunodeficiency virus type 1; Virological response.

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Cohort Studies
  • Drug Resistance, Multiple, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV-1 / drug effects
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones / administration & dosage
  • Quinolones / therapeutic use*
  • RNA, Viral / blood
  • Raltegravir Potassium / administration & dosage
  • Raltegravir Potassium / therapeutic use*
  • Retrospective Studies
  • Sustained Virologic Response*
  • Young Adult

Substances

  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones
  • RNA, Viral
  • Raltegravir Potassium
  • elvitegravir
  • dolutegravir