People with HIV often show persistent signs of cognitive impairment and abnormalities in brain structure, although the suppressive antiretroviral therapy (HAART) but does not appear to have a rapid decline as compared to individuals seronegative as they age, according to research presented at the Conference on Retroviruses and Opportunistic Infections last month in Seattle.
The neurocognitive disorder associated with HIV remains a poorly understood comorbidity in HIV-positive people. Although frank AIDS dementia is now rare among people who receive effective antiretroviral treatment; there are more subtle cognitive problems - some of which can only be revealed by specialized tests - remain common. Cognitive decline is a concern as the population of older people with HIV; Currently more than half of people living with HIV in the US have more than 50 years.
Aging and Cognitive Impairment
Hamza Coban the University of San Diego and colleagues examined the relationship between aging and neurocognitive performance over time by comparing the changes in older individuals and younger who had been on ART at least 2 years - the time when the problems related to assets , uncontrolled HIV replication should have been resolved.
The researchers analyzed 3313 people in the AIDS Clinical Studies Group (ACTG) in a Longitudinal Linked Randomized Study (ALLRT) cohort, which included 7 ACTG participants randomized in first-line ART trials.
Participants underwent annual neurocognitive assessment using tests that mensuravam different aspects of cognitive performance and memory. The overall performance was summarized using z scores in the test 4 (NPZ-4) standardized normative results from the general population of the same age.
The cohort included 3313 people, most menStarting antiretroviral drugs for the first time. A quarter were 30 years or less, about a third each were among the age groups of 31-40 and 41-50 years old, 10% belonged to the group aged between 50-60 years 2% they had over 60 years. Two-thirds had some education beyond the secondary level education; 8% were co-infected with hepatitis C virus (HCV), which can also affect neurocognitive function.
Upon first neurocognitive testing, over 90% had suppressed viral load.
Initial tests showed that 42% had impaired verbal learning Test and Hopkins 39% had impaired general NPZ-4 (average score -0,23). In the cohort as a whole, neurocognitive impairment decreased over time after the start of ART, 23% of the definition in the first evaluation to 13% in the last assessment.
But neurocognitive impairment probabilities increased with age in 18% for each decade older in a multivariate analysis. Having more than 31 40 years in the initiation of antiretroviral treatment and co-HCV infection was significantly associated with poorer results neurocognition, but no significant binding to the antiretroviral drug class first line.
To 2 years or more after the initiation of HAART, the older age remained a significant risk factor for neurocognitive impairment and age-related disability was observed despite viral suppression and despite the improvement in the overall cohort.
They suggested that the causes of age-related neurocognitive impairment may include ART aggravating the conditions commonly associated with aging as well as diabetes, hypertension and abnormal blood lipid profiles, and possibly more toxicity of the central nervous system in the elderly. In future studies, they recommended, they should observe the effects of inflammation, other co-infections, such as syphilis and cytomegalovirus, as well as obesity and cardiovascular risk factors.
Changes in HIV-positive people vs HIV-negative
The study of Coban showed that cognitive decline was associated with aging in ALLRT cohort, but this usually occurs when people grow older in the general population. Because people with HIV progression compared with the HIV-negative individuals? James Cole, from Imperial College London, Rosan van Zoest, the Institute for Global Health in Amsterdam, and his colleagues tried to answer that question.
This study analyzed longitudinal neuroimaging and neuropsychological data of HIV-positive participants in COBRA collaboration (Comorbidity in Relation to AIDS) and a group of Demographically similar HIV-negative, looking at each successfully treated HIV is associated with accelerated age-related changes to the structure and brain function.
The analysis included 134 HIV-positive people in centers in Amsterdam and London who were on ART with HIV RNA
Magnetic resonance imaging (MRI) and neuropsychological tests including language, memory, executive function, motor function and processing speed were performed at baseline and after two years.
Baseline MRI showed that people with HIV were less volume of abnormal brain gray matter and white matter microstructure compared to HIV negative individuals as well as a weaker cognitive function.
But there were no notable differences in age-related changes in HIV-positive and HIV-negative groups. Both groups showed a decline in neuroimaging measures. The HIV-positive people lost their 0,82% of brain volume per year, whereas the HIV-negative people lost 0,77%, not a significant difference.
The measures of cognitive function have not changed much in general. A measure of global cognition (T-score) increased somewhat in both groups, at + 0,8 the positive and HIV + group 0,5 in HIV-negative group. Attention was the only measure to show a significant difference in change rate between the two groups, increasing the HIV positive group and falling in HIV-negative group most similar to their scores.
HIV-positive people with virus suppressed on ART "showed abnormalities in measures of brain structure and function at the beginning," but "there was no difference in the dynamics of these measures over time among HIV positive and negative controls to HIV," they concluded The researchers. "Cognitive performance has not diminished over 2 years."
"Although we have previously found evidence of increased brain age in this cohort of people living with HIV," they continued, "this analysis does not find evidence of accelerated brain aging over time" in people with continued viral suppression on HAART.
cognitive changes in women
brain functions and structural changes in women with HIV may not be the same as those observed in HIV-positive men who have historically had a higher socioeconomic status and higher education levels.
Leah Rubin of the University of Illinois at Chicago and colleagues compared the cognitive trajectories of HIV-positive women with viral suppression on ART, HIV-positive women with poorly controlled HIV and HIV-negative women in the Women's Interagency HIV Study (WIHS). They hypothesized that women with viral suppression would leave up better than women with poorly controlled virus, however, worse than women not infected.
Among 2009 and 2015, a total of 932 WIHS participants underwent neurocognitive tests, including measures of learning, memory and attention at the beginning and then every two years.
Of these, 239 were HIV positive with viral suppression, 392 were HIV positive with no viral suppression, and 301 were HIV negative. The groups were demographically similar. The average age was about 45 years, about two-thirds were black and half had average or less education.
Virally suppressed women reported continued use of HAART over 4 years with superior adhesion to 90%, while in 44% unsuppressed group used it intermittently with 74% of grip. The median viral load was 48 copies / ml in the deleted group and 360 copies / ml in the group not suppressed. The current count CD4 was 657 437 cells and / 3 mm2 these groups, while the nadir counts were 244 170 cells and / mm3 respectively.
In general, HIV-positive women had significantly lower baseline T scores for the overall neuropsychological performance, as well as memory, attention and learning, compared with HIV-negative women.
Among women with HIV, people with viral suppression had higher scores in learning, memory and motor skills than women not suppressed, but overall performance was essentially the same and women not suppressed. Actually did better in a couple of measures, such as attention and fluency.
Having a diagnosis of AIDS and lower levels of CD4 they were associated with lower scores in some areas. Following spend more time with a suppressed viral load was associated with higher scores in most areas.
Over time, women in all three groups experienced declines in overall performance, memory, attention and learning. Women with HIV have seen a decrease in processing speed while HIV-negative women improved - the only area of improvement observed in any group. There was no consistent pattern in the slope of the declines in different areas in groups.
"The longitudinal findings confirm the persistent cognitive impairment despite continued viral suppression," the researchers concluded. "Group differences Standards indicate persistent vulnerability attention, learning, memory and fluency and greater vulnerability in motor skills over time, despite the ideal suppression among HIV-positive women."
Brain volume and brain vessel disease
The anatomical changes in the brain that may contribute to impair cognitive function in people with HIV are not well understood.
Ryan Sanford, of the Montreal Neurological Institute of McGill University, and colleagues evaluated along the brain volume in 46 people with HIV positive virus well-controlled and 31 HIV-negative individuals with demographic match. Approximately half were men, the average age was about 50 years 14 years and have had instruction in the general average. In the HIV positive group CD4 current nadir counts and 641 200 cells and / mm3 respectively.
Participants completed 2 sessions neuroimaging and neuropsychological tests conducted approximately 2 years apart. The assessment covered with 6 8 cognitive domains patterns. The standardized Z-scores were calculated for each test as well as neuropsychological overall score (NPZ-8).
On both visits, HIV-positive participants had significantly poorer cognitive performance than negative people with lower scores for NPZ-8 and executive function, attention, working memory and processing speed components.
However, there were no significant changes in NPZ-8 score over time in any group, or a difference in change rates between the groups. The HIV-positive group saw a greater improvement in memory and a tendency to a greater decline in executive function.
Similarly, the tensor-based morphometry showed a significant reduction in volume in the subcortical thalamus, caudate, putamen, globus pallidus and cerebral medium in HIV-positive people on both visits. But no big change in brain volume was observed over time in any region of any group, or different rates of change between groups. The CD4 lower nadir count was not significantly correlated with lower brain volumes.
"No evidence of ongoing brain injury or general cognitive decline was detected," the researchers concluded. "These findings support the hypothesis that cognitive and structural brain differences in HIV-positive patients occur most probably during the period of untreated infection, suggesting a possible neurocognitive benefits of early combination therapy initiation."
Finally, Dominique Costagliola the Sorbonne and INSERM in Paris and colleagues analyzed the prevalence of brain disease in people living with HIV compared to people not reactive to serological testing for HIV, people with 50 years or more.
The brain disease small vase - defined by abnormalities in the white matter, silent cerebral infarction (blocked blood supply) or micro bleeding - is a major cause of future vascular events such as stroke, cognitive impairment, frailty and low survival. Researchers noted as background.
This analysis included 456 HIV-positive people in the French ANRS EP51 MICROBREAK cohort 154 and HIV-negative people. About 80% were men and the median age was 56 years. Participants HIV-positive group were HAART suppressed viral load for at least one year. The median CD4 nadir counts and 655 195 cells and / mm3; they had coinfection with HCV. Most cardiovascular risk factors was observed more frequently among people with HIV, including hypertension and abnormal blood lipid levels as well as regular consumption of alcohol; Over 40% in both groups was smoking.
In this cross-sectional study, each participant received a single MRI, and the results were analyzed by 2 Neuroradiologists that were experienced without them knowledge of HIV serology.
The disease of small cerebral vessels was detected in 52% of HIV-positive participants and seronegative 36% of participants, a significant (adjusted odds ratio [OR] 2,3). Severe CSVD% was observed in 19 and 14%, respectively (adjusted OR 1,6).
But the impact of HIV differed according to age. HIV-positive people under the age of 54 years 5 were about times more likely, and those aged between 54 and 60 years were almost four times more likely to develop CVD compared to HIV-negative people; however, for people over 60 years there was essentially no difference (adjusted OR 5,3, 3,7 and 1,2, respectively).
In HIV, the age of 60, hypertension and CD4 count below 200 cells / mm3 were also associated with increased risk of CSVD, the researchers reported.
Eight March 2017
H Coban, Robertson K, Wu K, et al. Impact of advancing age on cognition in HIV-infected persons on the first suppressive regimen. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. abstract 343.
H Cole, MW Caan, J Underwood, R Zoest van, et al. Longitudinal analysis shows the evidence for accelerated aging brain in treated HIV. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. Abstract 32LB.
H Rubin, G Springer PM Maki, et al. Cognitive trajectories over 4 years among HIV-infected women with optimal viral suppression. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. abstract 350.
R Sanford, LK Fellows, L Collins, et al. Longitudinal assessment of brain regionally specific volume in treated HIV-infected patients. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. abstract 397.
The Moulignier, J Savatovsky, the Godin, Costagliola D, et al. Cerebral small-vessel disease in HIV-infected Patients well controlled on CART. Conference on Retroviruses and Opportunistic Infections. Seattle, February 13-16, 2017. abstract 75.