Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients.
Title | Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Ma, Q, Vaida, F, Wong, J, Sanders, CA, Kao, Y-ting, Croteau, D, Clifford, DB, Collier, AC, Gelman, BB, Marra, CM, McArthur, JC, Morgello, S, Simpson, DM, Heaton, RK, Grant, I, Letendre, SL |
Corporate Authors | CHARTER Group |
Journal | J Neurovirol |
Volume | 22 |
Issue | 2 |
Pagination | 170-8 |
Date Published | 2016 Apr |
ISSN | 1538-2443 |
Keywords | Adult, Alkynes, Anti-HIV Agents, Benzoxazines, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CHARTER, Cognitive Dysfunction, Coinfection, Cyclopropanes, Drug Therapy, Combination, Executive function, Female, Hepacivirus, Hepatitis C, HIV Infections, HIV-1, Humans, Internal, Lopinavir, Male, Memory, Middle Aged, Neuropsychological Tests, Ritonavir, Verbal Learning |
Abstract | Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n = 272, mean duration 17.9 months) or LPV/r (n = 173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p < 0.001), were less likely to have AIDS (p < 0.001) or hepatitis C virus (HCV) coinfection (p < 0.05), had higher CD4+ T cell nadirs (p < 0.001), had lower peak (p < 0.001) and current (p < 0.001) plasma HIV RNA levels, and were less likely to have detectable HIV RNA in cerebrospinal fluid (CSF) (p < 0.001). Overall, EFV users had worse speed of information processing (p = 0.04), verbal fluency (p = 0.03), and working memory (p = 0.03). An interaction with HCV serostatus was present: Overall among HCV seronegatives (n = 329), EFV users performed poorly, whereas among HCV seropositives (n = 116), LPV/r users had overall worse performance. In the subgroup with undetectable plasma HIV RNA (n = 269), EFV users had worse speed of information processing (p = 0.02) and executive functioning (p = 0.03). Substantial differences exist between EFV and LPV/r users in this observational cohort, possibly because of channeling by clinicians who may have prescribed LPV/r to more severely ill patients or as second-line therapy. Despite these differences, EFV users had worse functioning in several cognitive abilities. A potentially important interaction was identified that could indicate that the NC consequences of specific antiretroviral drugs may differ based on HCV coinfection. The complexity of these data is substantial, and findings would best be confirmed in a randomized clinical trial. |
DOI | 10.1007/s13365-015-0382-7 |
Alternate Journal | J Neurovirol |
PubMed ID | 26407716 |
PubMed Central ID | PMC4783211 |
Grant List | HHSN271201000036C / / PHS HHS / United States R01 MH58076 / MH / NIMH NIH HHS / United States R01 NS079166 / NS / NINDS NIH HHS / United States R03 DA022137 / DA / NIDA NIH HHS / United States R01 MH080150 / MH / NIMH NIH HHS / United States K24 MH097673 / MH / NIMH NIH HHS / United States R01 MH60720 / MH / NIMH NIH HHS / United States DA022137 / DA / NIDA NIH HHS / United States P50 DA026306 / DA / NIDA NIH HHS / United States R01 MH078748 / MH / NIMH NIH HHS / United States HHSN271201000030C / MH / NIMH NIH HHS / United States R01 MH83552 / MH / NIMH NIH HHS / United States U01 AI074521 / AI / NIAID NIH HHS / United States R01 MH092225 / MH / NIMH NIH HHS / United States P30 MH62512 / MH / NIMH NIH HHS / United States R01 MH78737 / MH / NIMH NIH HHS / United States R44 AI068543 / AI / NIAID NIH HHS / United States UM1 AI069434 / AI / NIAID NIH HHS / United States P50 DA26306 / DA / NIDA NIH HHS / United States UM1 AI069495 / AI / NIAID NIH HHS / United States U24MH100930 / MH / NIMH NIH HHS / United States R01 MH058076 / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States R01MH101017 / MH / NIMH NIH HHS / United States HHSN271201000030C / / PHS HHS / United States R01 MH78748 / MH / NIMH NIH HHS / United States AI068543 / AI / NIAID NIH HHS / United States R01 MH078737 / MH / NIMH NIH HHS / United States R01 NS072005 / NS / NINDS NIH HHS / United States P01 DA026146 / DA / NIDA NIH HHS / United States K08 MH098794 / MH / NIMH NIH HHS / United States R01 AI47033 / AI / NIAID NIH HHS / United States R01 AI090783 / AI / NIAID NIH HHS / United States R01 NR012907 / NR / NINR NIH HHS / United States U01 AI74521 / AI / NIAID NIH HHS / United States U01 MH83506 / MH / NIMH NIH HHS / United States R01 MH101017 / MH / NIMH NIH HHS / United States P01 AI057005 / AI / NIAID NIH HHS / United States R01NS079166 / NS / NINDS NIH HHS / United States U01 AI069495 / AI / NIAID NIH HHS / United States R01NS072005 / NS / NINDS NIH HHS / United States NR012907 / NR / NINR NIH HHS / United States R01 MH80150 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States P01 DA012065 / DA / NIDA NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States NS077384 / NS / NINDS NIH HHS / United States K08MH098794 / MH / NIMH NIH HHS / United States P01 DA12065 / DA / NIDA NIH HHS / United States P30 AI027757 / AI / NIAID NIH HHS / United States R01 MH083552 / MH / NIMH NIH HHS / United States R01 MH107345 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States R01 MH085608 / MH / NIMH NIH HHS / United States U10 NS077384 / NS / NINDS NIH HHS / United States R01 MH92225 / MH / NIMH NIH HHS / United States AI057005 / AI / NIAID NIH HHS / United States R01 AI047033 / AI / NIAID NIH HHS / United States R01 MH060720 / MH / NIMH NIH HHS / United States R43 AI068543 / AI / NIAID NIH HHS / United States AI69495 / AI / NIAID NIH HHS / United States AI27757 / AI / NIAID NIH HHS / United States |