Incidence and risk factors for neuropsychiatric events among Ghanaian HIV patients on long-term non-nucleoside reverse transcriptase inhibitor-based therapy

• Millions of patients living with HIV AIDS in sub-Saharan Africa are initiated on an efavirenz-based combination antiretroviral therapy which is frequently associated with neuropsychiatric toxicity.
• In this retrospective study involving 3999 Ghanaian HIV-infected patients initiating therapy between 2004 and 2010, neuropsychiatric toxicity was documented in 5.5% with a higher incidence among efavirenz recipients (7.6%) compared with nevirapine recipients (2.4%).
• Peak neuropsychiatric adverse events occurred within the first two months upon initiating therapy with some few further events occurring as later on during 90 months of follow-up.
• Up to 17% of patients reporting neuropsychiatric toxicity had treatment modifications as a result.

BackgroundNon-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) is associated with neuropsychiatric toxicity. Little is known about the risk of short- and long-term neuropsychiatric toxicity in sub-Saharan Africa, where NNRTIs are widely used in first-line combination ART. This observational study assessed the risk of neuropsychiatric toxicity in Ghanaian patients starting first-line ART between 2004 and 2010 at a single centre.MethodsIn this retrospective observational study, frequencies of documented neuropsychiatric toxicity events were assessed and time to events calculated using a Kaplan–Meier analysis. Associations of neuropsychiatric toxicity with specific NNRTIs and other explanatory variables were examined using Cox proportional hazards modelling.ResultsOf 3999 patients initiating NNRTI-based ART, who were followed for a median of 30 (0.25–90) months (11,237 person years), 218 (5.5%) reported symptoms of neuropsychiatric toxicity at a rate of 21.4 events per 1000 person-years (95% CI, 18.8–24.2/1000 py). Events were more common with efavirenz than nevirapine (7.6% versus 2.4%), were usually reported within the first 2 months of ART initiation and persisted up to 84 months in a few patients. The most commonly reported neuropsychiatric adverse drug reactions were insomnia (50%), headaches (8%), dizziness (7%) and abnormal dreams (6%). The factors independently associated with neuropsychiatric toxicity were BMI < 16 kg/m2 (aHR of 1.44 [95% CI, 1.02–2.03]) and use of efavirenz (aHR 3.29 [95% CI, 2.32–4.69]). Substitution of NNRTI on account of toxicity was reported in up to 17% of patients experiencing neuropsychiatric events.ConclusionsNNRTI-related neuropsychiatric toxicity, mainly due to efavirenz, was infrequently documented in this Ghanaian cohort under routine clinical care settings. Regimens with more favourable tolerability will be needed as first-line agents in sub-Saharan Africa in the coming years.