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This is Your Brain Off Drugs: Neurocognitive Function before and after Antiretroviral Treatment Discontinuation in Patients with High CD4 Nadir (ACTG A5170).
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Kevin Robertson*1, Zhaohui Su2, Amy Krambrink2, Scott Evans2, Diane Havlir3, David Margolis1, Daniel Skiest4, and ACTG 5170 team
UNC, Chapel Hill, NC, USA1 Harvard, Boston, MA, USA2 UCSF, San Francisco, CA, USA3 and Baystate Medical Center, Springfield, MA, USA4
Background: HIV enters the brain within days of primary infection and is found in CSF throughout the course of disease. Neurocognitive dysfunction is associated with systemic disease in untreated HIV. Prior studies have shown improved neurocognition with initiation of ART. 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 study of HIV-infected patients who elected to discontinue ART. Eligible subjects had CD4> 350 cells/mm3, HIV RNA viral load < 55,000 cp/mL, and were on ART (≥ 2 drugs) for ≥ 6 months. Subjects stopped ART at study entry and were followed for 96 wks with a neurocognitive exam (Trailmaking A/B and Digit Symbol) yielding a composite NPZ3 score where increasing scores reflect better performance. These tests assess psychomotor speed, attention, concentration, cognitive sequencing and shifting cognitive sets, all known to be altered by HIV. We further examined changes upon ART reinitiation in subjects that reinitiated prior to week 96.
Results: 167 subjects enrolled with a median nadir CD4 of 436mm3 and 4.5 median years on ART. Mean NPZ3 scores increased while subjects were off ART (increases of 0.22, 0.39, 0.53, 0.74 at weeks 24, 48, 72, and 96 respectively; all p-values<0.001). In analyses attempting to eliminate practice effects, significant increases beyond week 48 were noted. Significant increases were noted in subgroup analyses of subjects discontinuing EFV- and non-EFV-containing regimens. 46 subjects restarted ART prior to week 96. No significant changes in neurocognitive function were observed upon ART reinitiation.
Conclusion: This study found that patients with preserved immune function who discontinued ART did not experience decreases in neurocognitive function. Sensitivity analyses to adjust for practice effects and the selection bias of ART reinitiation do not completely explain this observation. These findings suggest that healthy patients who elect to stop ART early in disease will not suffer neurocognitive problems.
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