Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV

Abstract

Background: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants’ neuropsychiatric toxicity symptoms in a real-life setting. Methods: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. Results: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF ( P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. Conclusions: The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China

“…Our study showed that after excluding the economic burden between ARTs, BIC/FTC/TAF had significant better persistence compared with EFV + 3TC + TDF, which is consistent with previous real-world studies in western countries [ 10 , 11 ]. The treatment discontinuation of EFV + 3TC + TDF group is mainly due to safety reason, which is also shown in other studies reporting the neuropsychiatric side effects related with EFV [ 14 – 16 ]. Our study result is consistent with previous study findings showing EFV-based regimen to increase the treatment discontinuation risk due to neuropsychiatric side effects [ 17 – 19 ].…”

Advantages of switching to elvitegravir/cobicistat/emtricitabine/tenofovir therapy in virologically-suppressed people living with human immunodeficiency virus/acquired immune deficiency syndrome

“…After 48 weeks’ follow-up, no viral drug resistance or improvement in neuropsychiatric symptoms was found in patients switching from NNRTIs to E/C/F/TAF [6] . In our previous study, neuropsychiatric symptoms improved after switching from efavirenz [7] . In the present study, switching to E/C/F/TAF was associated with a lower proportion of hepatic insufficiency and increased triglyceride levels.…”

“…[6] In our previous study, neuropsychiatric symptoms improved after switching from efavirenz. [7] In the present study, switching to E/C/F/TAF was associated with a lower proportion of hepatic insufficiency and increased triglyceride levels. E/C/F/TAF therapy thereby appeared safe and may alleviate toxicity, while also leading to improvements in symptoms.…”