Dolutegravir (DTG) discontinuation due to neuropsychologic side effects (NPS) may be associated with preexisting psychiatric conditions of depression and anxiety, according to results of a study presented at the virtual Conference on Retroviruses and Opportunistic Infections, held from March 8 to 11, 2020.

DTG treatment has been associated with a higher rate for discontinuation as a result of NPS. Several associated factors for this association have been described, including older age, female sex, abacavir coadministration, higher DTG exposure, and pharmacokinetic- and pharmacodynamic-mediated variants. In addition, there has been an observed increase in the rates of moderate depression among patients who have switched to DTG. However, pre-existing psychiatric disorders have not previously been associated with a higher risk for NPS. Therefore, this prospective, observational study described the clinical features and outcomes of patients stopping DTG for NPS.

In total, 1455 participants starting DTG (naive and treated) were included from 2 Italian outpatient clinics. Clinical, therapeutic pharmacokinetics variables with the risk for DTG discontinuation due to NPS were analyzed. This analysis focused on patients who stopped DTG for NPS in terms of pre-existing psychiatric comorbidities and outcomes after drug withdrawal (resolution of symptoms was recorded at the first available follow-up after discontinuation).

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Of all included participants, after a median of 5.1 months, 526 participants discontinued DTG, with the most common reason being treatment switches with no efficacy or tolerability issues (n=274); 66 (4.5%) of participants discontinued DTG due to NPS. Of the 66 participants who discontinued DTG due to NPS, 21 (31.8%) participants had pre-existing psychiatric conditions, with the 2 most common being depression (12 [18.2%] patients) and anxiety (4 [6.1%] patients).


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The most common symptoms according to the preexisting psychiatric comorbidities of depression and anxiety were sleep disorders (35.6%), anxiety (28.9%), and headache (24.4%). Both headache (P =.039) and sleep disorders (P =.083) were associated with complete resolution of symptoms. After discontinuation, DTG was replaced with raltegravir (n=20), elvitegravir/c (n=19), darunavir/c (n=17), or rilpivirine (n=8), with the most complete resolution of symptoms observed with the elvitegravir/c replacement and the converse observed among patients who received rilpivirine.

Overall, the study concluded that NPS were heterogeneous, with sleep disorders, headache, and anxiety being the more incident among such effects, and no signal for a better switching strategy emerged.

Reference

Andrea C, Borghetti A, Milesi M, et al. Clinical features and outcomes of patients stopping STG for neuropsychiatric symptoms. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA.http://www.croiconference.org/sites/default/files/uploads/croi2020-boston-abstract-ebook.pdf. Accessed March 27, 2020.