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Neurocognitive Disorders Despite Undetectable HIV RNA
  Neurocognitive Disorders Despite Undetectable HIV RNA
Reported by Jules Levin
The CHARTER Study investigators in the poster at IAS said decline in cognition was associated with detectable HIV RNA in CSF and being HCV+. The MOST Study reported at CROI found that viral failure in plasma for patients on PI monotherapy, in this case Kaletra, was associated with increased levels of HIV RNA in CSF. Christine Katlama reported in her darunavir monotherapy study at IAS there were 3 CNS disorders on darunavir monotherapy with 2 cases of "discordant plasma/CNS symptomatic HIV replication in 2 patients on DRV/r monotherapy".
CROI: Unexpectedly high failure rate in LPV/r monotherapy arm, involving CNS, and association with low nadir CD4 count in the MOST study - (06/02/09)
"With the exception of one patient (CSF HIV RNA 82 cp/ml, randomized to CT) all patients had undetectable HIV RNA in CSF at baseline. At study termination, 3 patients had increased CSF VL while blood VL was < 400cp/ml Table 3. CSF VL was more than 1log above blood VL in the three isolated CSF failure cases."
IAS: CHARTER, Half in US HIV Group Have Neurocognitive Impairment, Which Improves With NNRTIs - written by Mark Mascolini - (07/29/09)
52% of 1555 HIV-infected people in the US CHARTER cohort had some type of neurocognitive impairment.
Among people with a nadir CD4 count above 200 and an undetectable viral load in blood, about 30% had some degree of impairment. That rate jumped to about 45% to 50% in people with a CD4 nadir above 200 and detectable viral load and in people with a CD4 nadir under 200 and detectable or undetectable viral load.
-- For the entire cohort, worse neurocognitive impairment correlated with (1) a lower nadir CD4 count, (2) an AIDS diagnosis, (3) worse comorbidity severity, and (4) taking antiretrovirals (which indicated more advanced HIV infection). For the 843 people in the incidental comorbidity group, worse neurocognitive impairment correlated with (1) nadir CD4 count below 200, (2) nadir CD4 count as a function of viral load, (3) and taking antiretrovirals.
--low nadir CD4 count may represent "a 'legacy' event whose neurologic consequences persist once triggered." If that speculation proves true, it would be another reason to promote prompter HIV diagnosis and treatment everywhere.
IAS: Persistence and Progression of HIV-associated Neurocognitive Impairment (NCI) in the Era of Combination Antiretroviral Therapy (CART) and the Role of Comorbidities: The CHARTER Study - (07/30/09)
OBJECTIVE: To examine the prevalence and predictors of HIV associated NCI in the CART era, within an HIV+ sample reflective of clinic populations with varying degrees of comorbidity.
Having a 'comorbidity' increased by 50-100% the rate of moderate of severe neurocognitive impairment in this analysis within CHARTER. Overall, 52% of patients had mild, moderate or severe cognitive impairment. For patients with 'incidental' comorbidity 40% had 'mild/moderate/severe' NCI, for patients with 'contributing' comorbidity 60% had 'mild/moderate/severe' NCI, and for parients with 'confounding' comorbidity 85% had 'mild/moderate/severe' NCI.
--Of note, patients with nadir CD4 >200 & undetectable plasma HIV RNA had a 30% probability of impairment, patients with nadir CD4 >200 or CD4 nadir <200 & detectable plasma VL had a 50% probability of impairment, and patients with CD4 nadir <200 & & undetectable plasma VL had a 45% risk for impairment. SO detectable viral load in plasma & low nadir CD4 appear to be associated with probability of impairment BUT even if VL in plasma is undetectable if nadir CD$ was <200 there still is 30% probability for impairment. SO what can patients do? There are anecdotally several lifestyle thongs to do: eat a mediterranean diet, vigorous physical exercise, and mental exercise. In this study having HCV was associated with neurocognitive decline.
IAS: One Third With Undetectable HIV RNA Have Asymptomatic Neurocognitive Impairment - written by Mark Mascolini - (07/20/09)
In this study in London, One third of 45 people taking suppressive antiretroviral therapy had asymptomatic neurocognitive impairment on a 40-minute computerized test [1]. younger people studied in this the British HIV clinic appeared to have worse impairment....Fourteen of 45 study participants (31%) had asymptomatic neurocognitive impairment, which affected about half of 24-to-39-year-olds studied but lower proportions of 40-to-49-year-olds, 50-to-56-year-olds, and 57-to-67-year-olds. This correlation with younger age reached statistical significance....investigators speculated that the higher neurocognitive impairment rate in younger adults could reflect their increased susceptibility to HIV's effects on the brain
High rates of asymptomatic neurocognitive impairment (aNCI) in HIV-1 infected subjects receiving stable combination anti-retroviral therapy (CART) with undetectable plasma HIV RNA
L. Garvey1,2, D. Yerrakalva1, A. Winston1,2 1Imperial College London, Department of Infectious Diseases, London, United Kingdom, 2Imperial College NHS Healthcare Trust, Department of HIV Medicine, London, United Kingdom
Background: In the post-CART era neurocognitive impairment (NCI) remains prevalent and can affect quality of life and adherence to antiretroviral-therapy. A paucity of data exists describing the prevalence of NCI in HIV-1 infected patients stable on CART.
Aim: To assess the proportion of HIV-1 infected subjects stable on CART with asymptomatic NCI (aNCI) in a large UK clinic.
Methods: Asymptomatic patients receiving CART with plasma HIV RNA < 50 copies/mL for at least 3 months were eligible to participate. A validated computerised neurocognitive assessment was performed (CogStateTM). aNCI was defined as per standard criteria: performance greater than 1SD below the age-stratified normative mean in at least two cognitive domains. Factors associated with the presence of aNCI were assessed by linear regression modelling.
Results: 45 (84% male) subjects participated. Mean age was 48 (SD 11) years and mean current CD4 count 546 (SD 271) cells/uL. aNCI was observed in14/45 (31%) subjects. No statistically significant associations were observed between presence of aNCI and current or nadir CD4 count, time since HIV diagnosis or type of HAART (NNRTI versus boosted PI) (p>0.27 for all observations). Interestingly aNCI was statistically significantly associated with younger age (p=0.03, r=0.32, 95%CI -0.026, -0.01, see figure 1).
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