Table 1 |.

Neurotoxicity of currently used antiretrovirals

Drug class	Examples	Clinical findings	Proposed mechanism of toxicity
NRTIs	Tenofovir alafenamide, abacavir	Psychosis, mania457, chronic kidney disease458,459	Inhibition of mitochondrial DNA polymerase-γ460, energy depletion and oxidative stress461–463, ER stress464, mitochondrial DNA depletion465,466
NNRTIs	Efavirenz, rilpivirine	Dizziness, insomnia, vivid dreams, headache, hallucinations, mania, depression467, anxiety468	Increased ER stress and mitochondrial toxicity469
Protease inhibitors	Ritonavir, lopinavir, darunavir	Nausea, insomnia, circumoral paraesthesias470	Reduced oligodendrocyte maturation471, astrocyte glutamate homeostasis472 and synaptic acetylcholine473, worse small vessel disease474, oxidative stress475
INSTIs	Dolutegravir, bictegravir, raltegravir, elvitegravir	Diarrhoea, nausea, headache476, neural tube defects477, insomnia478,479, depression, anxietya	Increased production of reactive oxygen species in astrocytes480, integrated stress response (elvitegravir)475
Entry inhibitors	Maraviroc, cenicriviroc, ibalizumab	Bronchitis, nasopharyngitis, oesophageal candidiasis481	No notable CNS toxicity reported482–485

ER, endoplasmic reticulum; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; INSTIs, integrase strand transfer inhibitors.

^aDolutegravir and bictegravir have a greater effect than raltegravir and elvitegravir^486–489.