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.
Acknowledgements
The San Diego HIV Neurobehavioral Research Center Group (Letendre et al, 2000, Antimicrob Agents Chemother 44: 2173–2175) is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the San Diego Veterans Affairs Healthcare System, and includes Director: Igor Grant, MD; Co-Directors: J. Hampton Atkinson, MD, and J. Allen McCutchan, MD; Center Manager: Thomas D. Marcotte, PhD; Naval Hospital San Diego: Mark R. Wallace, MD (P.I.); Neuromedical Component: J. Allen McCutchan, MD (P.I.), Ronald J. Ellis, MD, Scott Letendre, MD, Rachel Schrier, PhD; Neurobehavioral Component: Robert K. Heaton, PhD (P.I.), Mariana Cherner, PhD, Julie Rippeth, PhD, Joseph Sadek, PhD, Steven Paul Woods, PsyD; Imaging Component: Terry Jernigan, PhD (P.I.), John Hesselink, MD, Michael J. Taylor, PhD; Neuropathology Component: Eliezer Masliah, MD (P.I.), Dianne Langford, PhD; Clinical Trials Component: J. Allen McCutchan, MD, J. Hampton Atkinson, MD, Ronald J. Ellis, MD, PhD, Scott Letendre, MD; Data Management Unit: Daniel R. Masys, MD (P.I.), Michelle Frybarger, BA(Data Systems Manager); Statistics Unit: Ian Abramson, PhD (P.I.), Reena Deutsch, PhD, Deborah Lazzaretto, M.A.
The HIV Neurobehavioral Research Center is supported by Center award 5 P30 MH62512-01 from the National Institutes of Mental Health (NIMH). Dr. R. J.Ellis is supported by R01 MH58076.
The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.