Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort

Abstract

Objective: Prior studies have shown improved neurocognition with initiation of antiretroviral treatment (ART) in HIV. We hypothesized that stopping ART would be associated with poorer neurocognitive function. Methods:Neurocognitive function was assessed as part of ACTG 5170, a multicenter, prospective observational study of HIV-infected subjects who elected to discontinue ART. Eligible subjects had CD4 count Ͼ350 cells/mm 3 , had HIV RNA viral load Ͻ55,000 cp/mL, and were on ART (Ն2 drugs) for Ն6 months. Subjects stopped ART at study entry and were followed for 96 weeks with a neurocognitive examination.Results: A total of 167 subjects enrolled with a median nadir CD4 of 436 cells/mm 3 and 4.5 median years on ART. Significant improvements in mean neuropsychological scores of 0.22, 0.39, 0.53, and 0.74 were found at weeks 24, 48, 72, and 96 (all p Ͻ 0.001). In the 46 subjects who restarted ART prior to week 96, no significant changes in neurocognitive function were observed. Conclusion: Subjects with preserved immune function found that neurocognition improved signif-icantly following antiretroviral treatment (ART) discontinuation. The balance between the neurocognitive cost of untreated HIV viremia and the possible toxicities of ART require consideration. Classification of evidence:This study provides Class III evidence that discontinuing ART is associ- -1266GLOSSARY ACTG ϭ AIDS Clinical Trials Group; ART ϭ antiretroviral treatment; EFV ϭ efavirenz; HAART ϭ highly active antiretroviral therapy; HAD ϭ HIV-associated dementia; NP ϭ neuropsychological summary score; TI ϭ treatment interruption; VL ϭ viral load.

HIV-associated neurocognitive disorders: Antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes

“…[30,31] Clinical studies have also suggested potential ART neurotoxicity. For example, Robertson et al [14] showed significant improvement in cognitive function in a cohort of patients taken off ART. There are many possible reasons for the conflicting literature regarding cognitive changes on higher CPE regimens.…”

“…However, it may also relate to incomplete control of the virus and its effects on the CNS, and possibly to neurotoxicity of the antiretrovirals themselves. [14] One of the proposed reasons for the continually high incidence of HAND in the ART era relates to the difficulty posed by the bloodbrain barrier (BBB) for the passage of drugs into the CNS. Although previously investigated by many groups, a CNS penetration effectiveness (CPE) ranking system was formally proposed by Letendre et al [15] in 2008 and updated in 2010.…”

White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study

“…In addition, highly active antiretroviral therapy (HAART) appears to have a positive impact on the WM in the temporal lobe 15 but with some toxicity. 16 The effects of HAART in adolescents are also uncertain; this uncertainty may be attributed to high rates of nonadherence 17 and loss to follow-up. 18 Therefore, in this study, we used DTI combined with TractBased Spatial Statistics (TBSS; http://fsl.fmrib.ox.ac.uk/fsl /fslwiki/TBSS) analysis to investigate the integrity of WM microstructure in adolescents with vertically transmitted HIV infections undergoing current HAART.…”

Impact of current antiretroviral therapies on neuroAIDS

“…Chronic administration of efavirenz, nevirapine or lopinavir/ ritonavir resulted in neuro behavioral impairment in mice [39,40]. Interestingly, a recent study by Robertson et al reported that discontinuation of cART was associated with the improvement in neurocognitive performance [41]. The same group also found that median toxic concentration of abacavir, didanosine, etravirine and nevirapine in rat cortical neurons was similar in range to CSF concentrations [42].…”