Switching from a regimen containing abacavir/lamivudine or emtricitabine/tenofovir disoproxil fumarate to emtricitabine/tenofovir alafenamide fumarate does not affect central nervous system HIV-1 infection

Background: Despite suppressive antiretroviral therapy (ART), many HIV-infected individuals have low-level persistent immune activation in the central nervous system (CNS). There have been concerns regarding the CNS efficacy of tenofovir alafenamide fumarate (TAF) because of its low cerebrospinal fluid (CSF) concentrations and because it is a substrate of the active efflux transporter P-glycoprotein. Our aim was to investigate whether switching from emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or abacavir (ABC)/lamivudine (3TC) to FTC/TAF would lead to changes in residual intrathecal immune activation, viral load, or neurocognitive function. Methods: Twenty HIV-1-infected neuro-asymptomatic adults (11 on ABC/3TC and 9 on FTC/TDF) were included in this prospective study. At baseline, all participants changed their nucleoside analogues to FTC/TAF without any other changes in their ART regimen. We performed lumbar punctures, venipunctures, and neurocognitive testing at baseline and after three and 12 months. Results: During follow-up, there were no significant changes in CSF or plasma HIV RNA, CSF neopterin, CSF β2-microglobulin, IgG index, albumin ratio, CSF NFL, or neurocognitive function in assessed by Cogstate in any of the groups. Conclusion: This small pilot study indicates that switching to FTC/TAF from ABC/3TC or FTC/TDF has neither a positive, nor a negative effect on the HIV infection in the CNS

Higher plasma drug levels in elderly people living with HIV treated with darunavir

Background The proportion of elderly people living with HIV-1 (PLHIV) is rising. In older patients, comorbidities and concomitant medications are more frequent, increasing the risk of potential drug-drug interactions (PDDIs). Data on the pharmacokinetics of ART in individuals aged < 65 years of age are scarce. We compared plasma drug levels of ART, PDDIs, and sideeffects in PLHIV aged < 65 years of age, with controls > 49 years of age. Methods Patients < 65 years of age and controls > 49 years of age, all of whom were on stable treatment with atazanavir (ATV), darunavir (DRV), or efavirenz (EFV) were included cross-sectionally. Plasma drug levels of ART were analyzed, comorbidities, concomitant medication, adherence, and side-effects recorded, and PDDIs analyzed using drug interactions databases. Results Between 2013 and 2015, we included 100 individuals ≥ 65 years of age (study group) and 99 controls (<49 years of age). Steady-state DRV concentrations were significantly higher in the study group than in the control group (p = 0.047). In the ATV group there was a trend towards a significant difference (p = 0.056). No significant differences were found in the EFV arm. The DRV arm had a higher frequency of reported side-effects than the ATV and EFV arms in the study group (36.7% vs. 0% and 23.8% respectively (p = 0.014), with significant differences between DRV vs. ATV, and EFV vs. ATV). Conclusions Higher steady-state plasma levels of DRV and ATV (but not EFV) were found in PLHIV aged < 65 years of age, compared to controls >49 years of age