title: Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection.
abstract: Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1-infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI.NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because "practice effects" are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients.
authors.affiliation: Department of Neurosciences, University of California at San Diego, San Diego, California 92103, USA.
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Childers
authors.forename: Steven Paul
authors.initials: SP
authors.lastname: Woods
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Debralee
authors.initials: D
authors.lastname: Rosario
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Monica Rivera
authors.initials: MR
authors.lastname: Mindt
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
mesh_terms: D000339:Affect; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003071:Cognition; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000523:psychology*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D012307:Risk Factors; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral