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Switching from efavirenz-based to dolutegravir-based antiretroviral therapy (ART) improved cognitive function in people with HIV. This suggests efavirenz may cause neurotoxicity, and dolutegravir-based ART supports brain health.

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Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Pharmacology

Background:

  • HIV infection is linked to cognitive impairment, potentially due to HIV RNA cerebrospinal fluid (CSF) escape.
  • The World Health Organization recommends switching from efavirenz-based to dolutegravir-based antiretroviral therapy (ART) globally.
  • The cognitive effects of this ART switch, particularly dolutegravir's benefits, are not well understood.

Purpose of the Study:

  • To investigate the cognitive impact of switching from efavirenz-based to dolutegravir-based ART in adults with HIV.
  • To compare cognitive performance in people with HIV to those without HIV after the ART switch.
  • To assess the incidence of CSF HIV RNA escape during ART treatment.

Main Methods:

  • 178 adults with HIV on efavirenz-based ART and 95 HIV-negative controls underwent cognitive testing at baseline and 1-year follow-up.
  • Participants switched to dolutegravir-based ART; HIV-negative controls maintained their status.
  • Cerebrospinal fluid (CSF) samples were collected from people with HIV to quantify HIV RNA.

Main Results:

  • People with HIV showed significantly lower global cognitive performance at baseline compared to controls, but this difference disappeared at follow-up.
  • The rate of low cognitive performance decreased significantly in people with HIV after switching to dolutegravir-based ART.
  • Cognitive improvements in the HIV group were significantly greater than in the control group, suggesting a treatment effect.

Conclusions:

  • Cognitive improvements after switching to dolutegravir-based ART likely stem from reduced efavirenz neurotoxicity.
  • Dolutegravir-based ART is associated with improved cognitive function and lower rates of cognitive impairment in people with HIV.
  • CSF HIV RNA escape was infrequent and often transient, indicating good viral control and brain health on modern ART regimens.