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Prevalence of HIV-associated neurocognitive
disorders in the Multicenter AIDS Cohort Study
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from Jules: again, all these data reporting increased concerns for neurocognitive function worsening in HIV+ aging are in the context of no US federal & European govt attention to the increased services & clinical care these patients will need, not just for neurologic problems but for a host of worsening CVD, kidney, frailty, gait, housing, depression, mobility/ambulatory, fractures/falls.
MACS published in 2012: "Neurologic disorders incidence in HIV+ vs HIV- men"....http://www.natap.org/2012/HIV/102212_01.htm....."The incidence of all confirmed neurologic events by HIV status and decade of adult life is provided in table 2. Median age at first neurologic diagnosis among all participants alive in the HAART era was lower in HAART-treated HIV-positive vs HIV-negative men (48 vs 57 years old, p 0.001)......we have found that HIV-positive MSM in the HAART era experience a higher incidence of neurologic disease compared with their age-matched HIV-negative counterparts. HIV-positive men also experience neurologic diagnoses at an earlier age. The majority of neurologic disorders involved the peripheral nervous system, but neuroinvasive infections and cognitive disorders were also important burdens of neurologic disease in HIV-positive MSM. The higher burden of neurologic disorders experienced in HIV-positive MSM represents potentially treatable and preventable neurologic disease... Middle-aged and elderly HIV-positive individuals require in-depth clinical studies to fully understand the various mechanisms that may contribute to their excess burden of neurologic disease......Incidence of neurologic diagnoses was higher in HAART-treated HIV-positive vs HIV-negative men (younger than 40 years: 11.4 vs 0 diagnoses per 1,000 person-years [p < 0.001]; 40-49 years: 11.6 vs 2.0 [p < 0.001]; 50-60 years: 15.1 vs 3.0 [p < 0.001]; older than 60 years: 17.0 vs 5.7 [p < 0.01]). Excess neurologic disease was found in the categories of nervous system infections (p < 0.001), dementia (p < 0.001), seizures/epilepsy (p < 0.01), and peripheral nervous system disorders (p < 0.001), but not stroke (p = 0.60)."
Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study.....The results from this study suggest that HAND is common in HIV1individuals, mostly on cART with effective systemic virologic suppression. The frequency of HAND was 25%-33% from 2007 to 2012. This frequency of HAND is somewhat lower than the estimates for HAND in other large cohort studies that report a HAND prevalence of 47% excluding severely confounded cases.9......the proportion of HIV+ individuals >60 years of age was small. Further studies are needed in cohorts with more HIV+ individuals >60 years of age to evaluate the impact of age on HAND......Even though HAND appears to be a stable clinical diagnosis for the majority [not for 13%] of HIV+ individuals in this study (77%), there could still be ongoing CNS damage.......Indeed, neuroimaging studies within the MACS suggest that gray matter and white matter atrophy,13 as well as subcortical atrophy in the caudate and putamen, occur in HIV1 individuals with well-controlled immune status and systemic viral replication.14 Other studies using CSF markers of inflammation such as neopterin15 and markers of active axonal injury16 also suggest ongoing CNS injury in HIV1 patients on cART. Thus, a clinical diagnosis of HAND may not be as sensitive as neuroimaging or CSF markers of CNS injury......In a subset of individuals, approximately 13% showed clinical progression to more severe HAND. Risk factors for deterioration in clinical stage included hypercholesterolemia, suggesting that cerebrovascular disease [kidney, CVD, diabetes, hypertension] could be contributing to some of the cognitive impairment seen in these HIV1 individuals. Genetic factors, variability in test measurements, or concomitant age-related contributors to CNS injury could lead to cognitive deterioration in these HIV1 individuals......Our study evaluated the temporal progression of HAND over a 4-year period. Future studies will need to evaluate longitudinal changes in HAND over a longer period of time to characterize the potential contribution of comorbid conditions as well as to determine whether markers of CNS injury observed in imaging studies are associated with changes in the clinical characteristics of HAND. Future studies also should evaluate performance and rates of progression in specific neurocognitive domains......The MACS included gay/bisexual men and our results for HAND prevalence may not be applicable to other demographic groups of HIV+ individuals, especially women [from jules- 80% in MACS HIV+ are white-non-hispanic; history of IDU;50% in MACS had college education].
Unlike the pre-cART era, when HIV-associated cognitive impairment was a progressive condition within months, the diagnosis of MND and HAD is not progressive over a 4-year period in individuals with systemic virologic suppression for the majority (70%) of HIV1 individuals. These results are consistent with a prior study in the MACS cohort showing longitudinally preserved psychomotor speed performance in long-term asymptomatic HIV+ individuals with controlled HIV viremia over a 5-year period.10 An increase in the frequency of ANI was noted in 2011-2012. It remains to be determined whether this increased frequency of ANI persists in subsequent years, and whether this increased frequency is due to HIV itself or age related comorbid conditions unrelated to HIV infection.
A study in the CHARTER cohort found that a diagnosis of ANI was associated with an increased risk for progression to MND or HAD compared to HIV+ individuals with normal cognition.11 In our study, progression from ANI to either a MND or HAD stage was seen in 7/24 (29%) cases in HIV+ individuals over 4 years of follow-up. In contrast, 14/24 (58%) HIV1 individuals remained at ANI over 4 years, whereas 3/24 (13%) HIV1 individuals improved from ANI to normal cognition. Also, 18/147 (12%) HIV1 individuals with normal cognition progressed to MND or HAD. Thus, a diagnosis of ANI was associated with a 2-fold increased risk of symptomatic HAND (MND or HAD) compared to a diagnosis of normal cognition in HIV1 individuals, which is similar to the results in the CHARTER cohort. The results from the MACS suggest that the majority of HIV+ individuals with ANI stay at the same HAND stage over a 4-year time period and that progression to a more severe HAND stage is only slightly more common than improvement from ANI to normal cognition.
Another longitudinal study from the CHARTER cohort12 examining neurocognitive decline found that 61% of participants in CHARTER remained stable, 23% declined, and 17% improved over a mean time period of 35 months. These proportions are similar to the 77% of HIV+ individuals who remained stable, 13% who declined, and 10% who showed improvement in HAND stage over 4 years in our study.
Getting a handle on HAND in the era of cART.....MACS study adds to a growing body of evidence for the persistence and progression of HAND in the cART era

Neurology Dec 30 2015
Ronald A. Cohen, PhD, Bradford Navia, MD
From the Center for Cognitive Aging (R.A.C.), University of Florida, Gainsville; and the Department of Public Health (B.N.), Tufts University, Boston, MA.
Despite the effectiveness of combined antiretroviral therapy (cART) in suppressing HIV viral load and reducing cognitive impairment,1 for many chronically HIV-infected people, neurocognitive dysfunction remains a common problem, as several recent studies continue to show persistence and progression of cognitive impairment and brain injury.2,3
The study by Sacktor and colleagues4 further supports the importance of this problem but also highlights some interesting differences. In the Multicenter AIDS Cohort Study (MACS), HIV-associated neurocognitive disorder (HAND) occurred in 25%-33% of participants—a rate somewhat lower than that observed in other recent studies (e.g., approximately 40%-50% in CNS HIV Antiretroviral Therapy Effects Research [CHARTER] and HIV Neuroimaging Consortium [HIVNC]),2,5 probably reflecting demographic and clinical differences among these cohorts. These include less racial-ethnic diversity, less baseline disease severity (e.g., higher nadir CD4), and a greater proportion of gay/bisexual men than people with substance abuse in the MACS, which may also partially explain the lower progression rate. The mean age of the cohort (46 years) may also have some bearing on this issue, as declines in learning and memory may occur primarily among HIV-infected people over 55 years of age, whereas seronegative adults in this age range tend not to exhibit substantial declines.6 As progression between HAND stages requires a discrete shift between diagnostic categories that partly depends on the determination of activities of daily living impairment, it is possible that a proportion of the cohort may have experienced subtle cognitive and functional declines that do not manifest as a shift in HAND severity in the short term. Despite these limitations, the MACS study adds to a growing body of evidence for the persistence and progression of HAND in the cART era. As pointed out by the authors, further research is needed to evaluate these problems over a longer time period and the mechanisms underlying their persistence.
Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study
Neurology Dec 30 2015
Ned Sacktor et al
To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up.
Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification.
Results: The frequency of HAND for the 364 HIV+ individuals seen in 2007-2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007-2008, 2009-2010, and 2011-2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009-2010 to 2011-2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition.
Conclusion: HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period. excerpts-
A diagnosis of hypercholesterolemia was associated with an increased risk for worsening HAND stage (OR 2.8 [CI 1.3-5.9] [p = 0.01]).
Frequency of HAND stratified by age. For all 364 HIV1 individuals evaluated for HAND in 2007-2008, the overall frequencies of HAND when stratified by each decade of life in HIV1 individuals in the age ranges of 20-29 years (n 5 16), 30-39 years (n = 48), 40-49 years (n = 150), 50-59 years (n = 122), and 60-69 years (n 5 26) were 31%, 31%, 36%, 29%, and 27%, respectively, suggesting no increased frequency of HAND with each advancing decade. However, the overall frequencies of HAD (dementia) when stratified by each decade of life increased from 0% (20-29 years) and 2% (30-39 years) to 5% (40-49 years), 6% (50-59 years), and 8% (60-69 years), respectively.
At the 2007-2008 time periods, 41% of HIV+ individuals were ,50 years of age, and 59% of HIV+ individuals were >/=50 years of age. The overall frequencies of all HAND classification for HIV+ individuals <50 years of age during the 2007-2008 period, 2009-2010 period, and 2011-2012 period were 34%, 31%, and 31%, respectively. The overall frequencies of HAND for HIV+ individuals $50 years of age during the 2007-2008 period were 28%, 27%, and 28%, respectively. There was no significant change in the overall frequency of HAND over this 4-year period for either HIV+ individuals <50 years of age or for HIV+ individuals >/50 years of age. There was also no difference in the frequency of ANI, MND, or HAD across the 3 time periods for either HIV1 individuals <50 years of age or HIV+ individuals >/=50 years of age.

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