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HIV - Management of Neurologic Diseases Authors: Jessica Robinson-Papp, MD, David M. Simpson, MD () Last Reviewed: 10/20/11 (What's New ) This content is part of a free CME-certified online point-of-care resource, available at

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In patients with untreated HIV, HAART often markedly improves HIV-associated dementia (HAD).[Sacktor 1999; Dore 2003; Sacktor 2001] Unfortunately, however, patients with well-controlled HIV still develop HAD, and no treatment has yet to show efficacy in addition to that conferred by HAART. Minocycline was recently evaluated in a randomized, placebo-controlled trial in 107 persons with HIV-associated cognitive impairment and found to be ineffective.[Sacktor 2011] There are currently conflicting data regarding the relationship between antiretroviral penetration across the blood-brain barrier, the likelihood of suppressing cerebrospinal fluid HIV-1 RNA, and the potential for improving cognitive performance in patients with HAD. A recent included 37 individuals with mild to moderate neuropsychiatric impairment at baseline who started antiretroviral therapy and subsequently were evaluated for 48 weeks to determine changes in neuropsychiatric function.[Cysique 2009] The study found rapid and sustained cognitive improvements upon HAART initiation and, in multivariate analysis, identified higher antiretroviral central nervous system (CNS) penetration as well as poorer baseline function to be predictors of neuropsychological improvement. In a second study of 101 patients with advanced HIV initiating or changing a new potent antiretroviral regimen, the association between CNS penetration effectiveness of their treatment regimen and neuropsychological outcomes were evaluated.[Marra 2009a] This study showed contrasting results, finding that antiretroviral regimens with better CNS penetration were associated with poorer neurocognitive performance despite their efficacy in controlling CSF viral replication. A recent cohort study from the UK investigated the relationship between the incidence of CNS disease (HIV encephalopathy, progressive multifocal leukoencephalopathy, cerebral toxoplasmosis, and cryptococcal meningitis) during 1996-2008 and the use of antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores.[Garvey 2011] Scores were calculated using the system developed by Letendre and colleagues,[Letendre 2010] whereby each antiretroviral drug is given a CPE score between 1 (low CNS penetration) and 4 (high CNS penetration) and a regimen total calculated. There was no significant difference in the incidence of CNS disease among patients receiving regimens with higher vs lower CPE scores, although CNS diseases occurred numerically more frequently in patients receiving HAART regimens with CPE scores ≤ 4 and less frequently in those with scores ≥ 10. A French study compared survival rates following diagnosis of an HIV-related CNS disease (defined as in the previous UK study) according to the CPE score of patients’ antiretroviral therapy.[Lanoy 2011] In the pre- and early-HAART era, a higher CPE score was associated with increased survival following a severe neurologic event. However, in the late HAART period, there was no association between CPE score and mortality risk overall. A prospective cohort study from Canada also found CPE rank did not correlate with global neuropsychological function among HIV-infected patients receiving antiretroviral therapy (Capsule Summary).[Rourke 2011] Some clinicians have suggested changing the HAART regimen in patients with CNS disease to include agents with high CNS penetration (Table 1).[Letendre 2004; Varatharajan 2009] Given the conflicting data, further studies are needed to establish the clinical utility of this ©2003-2013 approach. Clinical Care Options, LLC. All Rights Reserved.
Table. Antiretroviral Agents and CNS Penetration Effectiveness Level[Letendre 2010]

Lev el 4 (High Penetration) Zidov udine Nev irapine Indinav ir/ritonav ir

Lev el 3 (Intermediate Penetration) Abacav ir Emtricitabine Efav irenz

Lev el 2 (Intermediate Penetration) Stav udine Lamiv udine Fosamprenav ir

Lev el 1 (Low Penetration) Didanosine Tenofov ir Zalcitabine of Specific Disease States/ch38_pt_Neurologic/Pages/Page 2/Subpage 3.aspx#


com/inPractice/HIV/Management of Specific Disease States/ch38_pt_Neurologic/Pages/Page 2/Subpage 3. or the companies prov iding educational grants.Free Resource . Psychiatric Disorders Disclaimer: The materials published on the Clinical Care Options Web site ref lect the v iews of the rev iewers or authors of the CCO material.2/24/13 Fosamprenav ir ± ritonav ir Indinav ir Darunav ir/ritonav ir Lopinav ir/ritonav ir Marav iroc Raltegrav ir inPractice . the accredited prov ider. LLC.aspx# 2/2 . not those of Clinical Care Options.clinicaloptions. The materials may discuss uses and dosages f or therapeutic products that hav e not been approv ed by the United States Food and Drug Administration. Readers should v erif y all inf ormation and data bef ore treating patients or using any therapies described in these materials. www.Treatment Atazanav ir ± ritonav ir Nelfinav ir Ritonav ir Saquinav ir ± ritonav ir Tipranav ir/ritonav ir Enfuv irtide Keywords: HIV and Older Patients. A qualif ied healthcare prof essional should be consulted bef ore using any therapeutic product discussed. Neurologic Complications.