Abstract and Introduction
Objective: Doravirine is an alternative treatment option for individuals who do not tolerate efavirenz. We assessed efficacy, safety, and CNS effects in adults with HIV-1 and CNS complaints who switched from an efavirenz-based regimen to a doravirine-based regimen.
Design: Multicenter, double-blind, randomized trial (NCT02652260).
Methods: Virologically suppressed adults receiving efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF), or its components, with ongoing EFV-associated CNS toxicity grade 2 or higher (DAIDS criteria) were switched to doravirine/lamivudine/tenofovir (DOR/3TC/TDF) on day 1 (Immediate Switch Group [ISG]) or after 12 weeks (Deferred Switch Group [DSG]). CNS toxicity data were collected by self-administered questionnaire. The primary endpoint was the proportion of participants with any grade 2 or higher CNS toxicity at week 12. Secondary endpoints included virologic response and effect on fasting lipids.
Results: Eighty-six participants (58% men, 56% black, median age 41 years, median 4 years on prior EFV regimen) were enrolled (43 ISG, 43 DSG) and included in the analyses. At week 12, 42% of ISG and 37% of DSG had at least 1 grade 2 or higher CNS toxicity [difference 4.7%, 95% CI (−16 to 25%); P = 0.33]. At 24 weeks postswitch, HIV-1 RNA less than 50 copies/ml was maintained in 95.3% of participants, and fasting lipids were significantly decreased (LDL-cholesterol −11.0, non-HDL-cholesterol −13.2, HDL-cholesterol −7.7, total cholesterol −20.9, and triglycerides −13.0 mg/dl).
Conclusion: In participants who had CNS complaints while receiving EFV/FTC/TDF, improvement in CNS toxicities attributable to EFV was not significantly different after switching to DOR/3TC/TDF compared with remaining on EFV/FTC/TDF. Virologic efficacy was maintained and lipid profiles improved after switching to DOR/3TC/TDF.
Doravirine (DOR) is a next-generation nonnucleoside reverse transcriptase inhibitor approved for the initial treatment of HIV-1 or to replace the current antiretroviral regimen in those who are virologically suppressed but desire a change in treatment. In clinical trials of treatment-naïve adults, DOR-based regimens have demonstrated noninferior efficacy and a superior lipid profile compared with darunavir-based regimens and efavirenz (EFV) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). DOR-based regimens have also demonstrated significantly fewer neuropsychiatric events than EFV-based regimens in parallel-group, direct comparison trials.[2,3] In virologically suppressed adults with HIV-1 who switched from a stable antiretroviral regimen, DOR with lamivudine (3TC) and TDF (DOR/3TC/TDF) maintained virologic suppression for 48 weeks with a favorable safety profile.
Psychiatric and cognitive disorders are common in people with HIV (PWH)[5–7] and may have many underlying causes, including psychosocial factors (including HIV-related stigma, social isolation, early life stress, and the burden of living with a chronic disease), lifestyle factors, such as recreational drug and alcohol use, and the adverse effects of antiretroviral therapy.[8–11] Neuropsychiatric events are the most frequent side effects of EFV and the most common reason for switching from EFV to another treatment regimen.[12,13] Although most of these events resolve spontaneously within weeks of starting treatment, they are persistent in some people, leading to reductions in quality of life. We evaluated CNS effects, antiretroviral efficacy, and clinical and laboratory safety outcomes in adults with HIV-1 who had CNS complaints while on an EFV-based regimen and then switched to DOR/3TC/TDF.
AIDS. 2021;35(5):759-767. © 2021 Lippincott Williams & Wilkins
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