Background
Dual-drug therapy with dolutegravir/lamivudine (DTG/3TC) is effective in achieving viral suppression in the blood, but its impact on HIV infection in the central nervous system (CNS) remains insufficiently explored. In this study, we aimed to investigate its effect in the CNS through assessment of cerebrospinal fluid (CSF) in individuals switching to DTG/3TC from a three-drug regimen.
Methods
The Gothenburg HIV CSF Study Cohort comprises a longitudinal study investigating HIV infection in the CNS. From this cohort, we retrospectively included all adult individuals who were on suppressive antiretroviral therapy and who switched to DTG/3TC and who also had undergone lumbar punctures up to one year before and up to two years after. CSF NfL levels were measured by ELISA, HIV RNA quantitative PCR was performed using Cobas 6800. ß2-microglobulin was measured using nephelometry, IgG using immunoturbidimetry. Other analyses were performed using standard laboratory methods.
Results
Lumbar punctures were performed in 20 of the 119 individuals with HIV who switched to DTG/3TC between 2017 and 2023. All were virally suppressed (< 50 HIV RNA copies/mL) in blood and CSF at the time of switch. Fifteen were on a regimen containing an integrase inhibitor at baseline. Seven participants were female. Median age at switch was 55 years. All participants remained suppressed in blood throughout the follow-up period, mean 384 days, while one patient had an asymptomatic minor increase of CSF HIV RNA to 70 copies/ml without elevation of CSF white blood cell count or NfL. When age adjusted to 50 years, mean CSF NfL levels were 528 ug/ml at baseline and 520 ug/ml at follow-up. The small difference was not significant. Neither were any significant differences observed in albumin ratio, IgG index, CSF ß2-microglobulin, CSF white blood cell count, between baseline and follow-up.
Conclusions
In this study, we observed no evidence of neuronal injury, as measured by NfL, or any other marker of CNS injury or inflammation following the switch to DTG/3TC. The results will be further explored by investigating additional injury and inflammatory biomarkers in CSF, as well as NfL and other CNS injury markers in plasma, in the entire cohort who switched to DTG/3TC.
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