Review of functional MRI in HIV : effects of aging and medication

HIV-associated neurocognitive disorder (HAND) is a frequently occurring comorbidity of HIV infection. Evidence suggests this condition starts subclinical before a progression to a symptomatic stage. Blood oxygenated level dependent (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in an early stage and might therefore be useful to evaluate the effect of HIV infection on brain function. An extensive literature search was performed in June 2015. Eligibility criteria for included studies were as follows: (1) conducting with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative control group. A total of 19 studies were included in the review including 931 participants. Differences in activation between HIV-positive and -negative participants were found when testing multiple domains, i.e., attention, (working) memory, and especially executive functioning. Overall, HIV-positive patients showed hyperactivation in task-related brain regions despite equal performances as controls. Task performance was degraded only for the most complex tasks. A few studies investigated the effect of aging on fMRI, and most of them found no interaction with HIV infection. Only three studies evaluated the effect of combination antiretroviral therapy (cART) on functional data suggesting an increase in activation with the use of cART. fMRI is a sensitive instrument to detect subtle cognitive changes in HIV patients. Open questions remain regarding the effects of cART on fMRI and the effects of aging on fMRI

Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients : A Randomized Controlled Trial

BACKGROUND: Efavirenz is well known for its clinical cognitive side-effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing Efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing Efavirenz. SETTING: a randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug- versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes. METHODS: virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA. RESULTS: 14 control and 34 switch subjects completed the study. There were no differences at baseline. Group-analysis demonstrated a significantly better improvement for the switch group on the domains attention (p=0.041) and speed of information processing (p=0.014). Normative comparison analyses showed that 5 out of the 34 patients who switched (15%) improved on NPA-score as compared to the control group. Interestingly, subjective improvement after discontinuing Efavirenz made 74% of the switch group chose for a regime without Efavirenz after study completion. CONCLUSION: switching from Atripla to Eviplera resulted in objective cognitive improvement on group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients that would benefit from discontinuing Efavirenz

Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients : A Randomized Controlled Trial

Background:Efavirenz is well known for its clinical cognitive side effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing efavirenz.Setting:A randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes.Methods:Virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA.Results:Fourteen control and 34 switch subjects completed the study. There were no differences at baseline. Group analysis demonstrated a significantly better improvement for the switch group on the domains attention (P = 0.041) and speed of information processing (P = 0.014). Normative comparison analyses showed that 5 of the 34 patients who switched (15%) improved on NPA score as compared to the control group. Interestingly, subjective improvement after discontinuing efavirenz made 74% of the switch group chose for a regime without efavirenz after study completion.Conclusions:Switching from Atripla to Eviplera resulted in objective cognitive improvement on the group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients who would benefit from discontinuing efavirenz

Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients : A Randomized Controlled Trial

BACKGROUND: Efavirenz is well known for its clinical cognitive side-effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing Efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing Efavirenz. SETTING: a randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug- versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes. METHODS: virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA. RESULTS: 14 control and 34 switch subjects completed the study. There were no differences at baseline. Group-analysis demonstrated a significantly better improvement for the switch group on the domains attention (p=0.041) and speed of information processing (p=0.014). Normative comparison analyses showed that 5 out of the 34 patients who switched (15%) improved on NPA-score as compared to the control group. Interestingly, subjective improvement after discontinuing Efavirenz made 74% of the switch group chose for a regime without Efavirenz after study completion. CONCLUSION: switching from Atripla to Eviplera resulted in objective cognitive improvement on group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients that would benefit from discontinuing Efavirenz

The Montreal Cognitive Assessment–Basic (MoCA-B) is not a reliable screening tool for cognitive decline in HIV patients receiving combination antiretroviral therapy in rural South Africa

Background HIV-associated neurocognitive disorders (HAND) are frequently occurring comorbidities in HIV-positive patients, diagnosed by means of a neuropsychological assessment (NPA). Due to the magnitude of the HIV-positive population in Sub-Saharan Africa, easy-to-use cognitive screening tools are essential. Methods This was a cross-sectional clinical trial involving 44 HIV-positive patients (on stable cART) and 73 HIV-negative controls completing an NPA, the International HIV Dementia Scale (IHDS), and a culturally appropriate cognitive screening tool, the Montreal Cognitive Assessment–Basic (MoCA-B). HAND were diagnosed by calculating Z-scores using internationally published normative data on NPA, as well as by using data from the HIV-negative group to validate the MoCA-B. Results One hundred and seventeen patients were included (25% male, median age 35 years, median 11 years of education). A moderate correlation was found between the MoCA-B and NPA total Z-score (Pearson's r = 0.36, p = 0.02). Area under the curve (AUC) values for MoCA-B and IHDS were 0.59 and 0.70, respectively. The prevalence of HAND in HIV-positive patients was 66% when calculating Z-scores using published normative data versus 48% when using the data from the present HIV-negative cohort. Conclusion The MoCA-B appeared not to be a valid screening tool for HAND in this setting. The prevalence of HAND in this setting is high, but appeared overestimated when using published norms

The Montreal Cognitive Assessment–Basic (MoCA-B) is not a reliable screening tool for cognitive decline in HIV patients receiving combination antiretroviral therapy in rural South Africa

Background HIV-associated neurocognitive disorders (HAND) are frequently occurring comorbidities in HIV-positive patients, diagnosed by means of a neuropsychological assessment (NPA). Due to the magnitude of the HIV-positive population in Sub-Saharan Africa, easy-to-use cognitive screening tools are essential. Methods This was a cross-sectional clinical trial involving 44 HIV-positive patients (on stable cART) and 73 HIV-negative controls completing an NPA, the International HIV Dementia Scale (IHDS), and a culturally appropriate cognitive screening tool, the Montreal Cognitive Assessment–Basic (MoCA-B). HAND were diagnosed by calculating Z-scores using internationally published normative data on NPA, as well as by using data from the HIV-negative group to validate the MoCA-B. Results One hundred and seventeen patients were included (25% male, median age 35 years, median 11 years of education). A moderate correlation was found between the MoCA-B and NPA total Z-score (Pearson's r = 0.36, p = 0.02). Area under the curve (AUC) values for MoCA-B and IHDS were 0.59 and 0.70, respectively. The prevalence of HAND in HIV-positive patients was 66% when calculating Z-scores using published normative data versus 48% when using the data from the present HIV-negative cohort. Conclusion The MoCA-B appeared not to be a valid screening tool for HAND in this setting. The prevalence of HAND in this setting is high, but appeared overestimated when using published norms

Screening tools for HIV-associated neurocognitive disorders among adults living with HIV in sub-Saharan Africa: A scoping review [version 1; peer review: 1 approved, 1 approved with reservations]

Abstract: Background: People living with HIV are at risk of developing HIV-associated neurocognitive disorders (HAND) which adversely affects their quality of life. Routine screening of HAND in HIV care is recommended to identify subtle changes in cognitive functioning and allow for early interventions. However, HAND detection is rarely done in sub-Saharan Africa (SSA), partly due to a lack of adequately standardized screening tools. This review was conducted to identify the commonly used screening tools for HAND in SSA and document their psychometric properties and diagnostic accuracy. Methods: We searched Ovid Medline, PsycINFO and Web of Sciences databases for empirical studies published from 1/1/1980 to 31/8/2018 on HAND among adults living with HIV in SSA. Results: We identified 14 eligible studies, of which 9 were from South Africa. The International HIV Dementia Scale (IHDS) was the most frequently reported tool, being used in more than half of the studies. However most studies only reported the diagnostic accuracy of this and other tools, with specificity ranging from 37% to 81% and sensitivity ranging from 45% to 100%. Appropriate data on construct validity and reliability of tools was rarely documented. Although most tools performed well in screening for severe forms of HAND, they lacked sensitivity and specificity for moderate forms of HAND. NeuroScreen, one of the newer tools, yielded good diagnostic accuracy in its initial evaluation in South Africa (81% to 93% sensitivity and 71% to 81% specificity). Conclusions: This review identified a lack of adequately standardized and contextually relevant HAND screening tools in SSA. Most screening tools for HAND used in SSA possess inadequate psychometric properties and diagnostic accuracy. There is a need for further validation of existing tools and development of new tools to make them sensitive and specific enough to identify both severe and moderate forms of HAND in SSA

Correlates of Executive Dysfunction in HIV

Despite advancements in combination antiretroviral therapy rates of mild neurocognitive impairment remain elevated amongst persons living with HIV (PLWH). Concomitant with the greater rate of survival into old age PLWH show accelerated cognitive Aging in multiple domains. Executive function is among the domains where early onset of decline is most evident. This chapter will discuss what are known correlates of executive dysfunction in PLWH in this era of antiretroviral therapy. The goal of this chapter is to expand on what is known regarding HIV disease severity and executive dysfunction to provide a more nuanced look at how other central and peripheral biomarkers, psychosocial and behavioral risk factors relate to deficits in inhibition, updating and working memory, cognitive set-shifting, and mental flexibility