CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: There was substantial prevalence of neurocognitive impairment at baseline in HIV+ ART naïve participants in diverse RLS. With ART, there were significant overall reductions in neurocognitive impairment over time, especially in those with moderate and severe impairments. The observed changes with ART may reflect both improvement and learning effect. ART in RLS led to reductions in neurocognitive impairment, and would likely lead to improved productivity and quality of life. A5271 provides infrastructure in diverse RLS, a much needed resource for clinicians and researchers conducting neurological and neuropsychological assessments. 452 High Frequency of Dementia in Antiretroviral-Naïve HIV+ Individuals in Rural Uganda Ned Sacktor 1 ; Deanna R. Saylor 1 ; Gertrude Nakigozi 2 ; Noeline Nakasujja 3 ; Xiangrong Kong 4 ; Kevin Robertson 5 ; Ronald H. Gray 4 ; Maria J.Wawer 4 1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 Rakai Health Sciences Program, Entebbe, Uganda; 3 Makerere University College of Health Sciences, Kampala, Uganda; 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 5 University of North Carolina, Chapel Hill, NC, US Background: HIV dementia was seen in 31% of 81 antiretroviral (ARV) naïve HIV+ individuals in a previous study in Kampala, Uganda. The frequency and risk factors for each stage of HIV-associated neurocognitive disorder (HAND), i.e., asymptomatic neurocognitive disorder (ANI), mild neurocognitive disorder (MND), and HIV dementia (HAD), in rural Sub-Saharan Africa is largely unknown. The objective of this study was to evaluate the frequency of and risk factors for HIV dementia in rural Rakai, Uganda where HIV subtypes D and A predominate. Methods: 299 ARV naïve HIV+ and 210 HIV- individuals from the Rakai Community Cohort Study received detailed neurological history, examination, neuropsychological tests (including tests of verbal learning and memory, motor, psychomotor speed, executive function, and verbal fluency), functional assessments, CD4 count, and plasma viral load. HAND stage was determined using Frascati criteria combining clinical, neurological, functional, and neuropsychological test data. Results were compared to HIV- normative data obtained from the prior study in Kampala, Uganda. Results: Demographics for HIV+ individuals were as follows: age [Mean (SD) = 36 (9) years, male gender %=51%, Education ≤ 4 th grade %= 47%, CD4 count [Mean (SD) = 309 (159)]. There was no difference in age, gender, or education between HIV+ and HIV- individuals. HIV+ individuals were more likely to have dementia (27%) compared to HIV- individuals (7%), (p <0.001). There were no differences in less severe HAND categories between the HIV+ and HIV- groups. Risk factors for dementia included advanced age (p=< 0.001), subjective memory problems (p= 0.03), HIV seropositivity (p=<0.001), depression symptomatology (p=<0.001), and impaired performance on the International HIV Dementia Scale screening test (p=<0.001). Conclusions: In one of the largest studies of cognitive performance and HAND in rural Sub-Saharan Africa, HIV+ individuals were more likely to have dementia compared to demographically matched HIV- individuals. Future studies will evaluate the frequency of HAND using HIV- normative data currently being obtained in Rakai, the association of HIV dementia and subtype, and response to ARV treatment. 453 Validation of the International HIV Dementia Scale Screening Tool for HAND in Uganda Megan M. Hosein 1 ; Deanna Saylor 1 ; Gertrude Nakigozi 2 ; Noeline Nakasujja 3 ; Xiangrong Kong 4 ; Kevin Robertson 5 ; Ronald H. Gray 4 ; Maria J.Wawer 4 ; Ned Sacktor 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 Rakai Health Sciences Program, Kalisizo, Uganda; 3 Makerere University College of Health Sciences, Kampala, Uganda; 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 5 University of North Carolina Chapel Hill, Chapel Hill, NC, US Background: HIV-associated neurocognitive disorders (HAND) are prevalent and often under-diagnosed complications of HIV. The International HIV Dementia Scale (IHDS) has been validated as a useful screening tool for HIV-associated dementia (HAD) in a number of settings, including Kampala, Uganda. However, little is known about the utility of the IHDS in rural sub-Saharan Africa. The objective of this study was to assess the validity of the IHDS as an appropriate screening tool for detecting different levels of HAND in the rural district of Rakai, Uganda. Methods: 299 HIV+ antiretroviral treatment (ART) naïve participants in the Rakai Community Cohort Study underwent comprehensive standardized neurological, neuropsychological and functional assessments, including the IHDS. HAND stages were determined based on the Frascati criteria. The diagnostic validity of the IHDS was assessed by determining the sensitivity, specificity, predictive values and area under the ROC curve (AUC) for IHDS cut-off scores of 9, 9.5 and 10 (lower score= worse performance). Results: Participants’ demographics were: Mean(SD) age = 36(9) years; Male = 51%; Education ≤ 4 th grade = 47%; Mean(SD) CD4 count = 309(159). For detecting any level of HAND [asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HAD], an IHDS cut off of ≤ 9 had a sensitivity and specificity of 60% and 71% (AUC 0.66), while a cut-off of ≤ 9.5 had a sensitivity and specificity of 67% and 64% (AUC 0.66), and a cut-off of ≤ 10 had a sensitivity and specificity of 80% and 55% (AUC 0.68). For detecting symptomatic HAND (MND and HAD), a ≤ 9 cut-off had a sensitivity and specificity of 62% and 62% (AUC 0.62), ≤ 9.5 had a sensitivity and specificity of 70% and 54% (AUC 0.62), and ≤ 10 had a sensitivity and specificity of 83% and 44% (AUC 0.64). For detecting HAD, an IHDS ≤ 9 cut-off had a sensitivity and specificity of 75% and 54% (AUC 0.65), ≤ 9.5 had a sensitivity and specificity of 80% and 46% (AUC 0.63), and ≤ 10 had a sensitivity and specificity of 90% and 32% (AUC 0.61). Conclusions: The IHDS is a sensitive and potentially useful screening tool for neurocognitive impairment in rural Uganda. When used for screening in a setting with comprehensive neuropsychological testing to confirm a HAND diagnosis, the ≤ 10 cut-off may be most useful as it provides the highest sensitivity. However, if further neuropsychological testing is unavailable, the higher specificity of a ≤ 9 cut-off may be more appropriate, particularly for HIV dementia screening. 454 Cerebrospinal Fluid Cytokines and HIV-Associated Neurocognitive Disorders in Uganda Mahsa Abassi 1 ; Gertrude Nakigozi 3 ; Noeline Nakasujja 2 ; Xiangrong Kong 4 ; David B. Meya 2 ; Kevin Robertson 5 ; Ronald H. Gray 4 ; Maria J.Wawer 5 ; Ned Sacktor 5 ; David R. Boulware 1 1 University of Minnesota, Minneapolis, MN, US; 2 Infectious Disease Institute, Kampala, Uganda; 3 Rakai Health Sciences Program, Entebbe, Uganda; 4 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 5 Johns Hopkins University School of Medicine, Baltimore, MD, US Background: In antiretroviral (ARV) naïve HIV+ individuals and HIV subtype B infection in the US, HIV associated neurocognitive disorder (HAND) is associated with increased cerebrospinal fluid (CSF) inflammatory cytokines. To better understand the neurocognitive effects of HIV in Uganda where HIV subtypes D and A predominate, we compared the expression of varying cytokines and neurodegenerative biomarkers in the CSF of ARV naïve HIV+ adults in Rakai, Uganda. Methods: Participants (78) from the Rakai Community Cohort Study in Uganda, who were HIV+, age >20 years, and ARV naïve underwent CSF biomarker profiling via multiplex assay, assessing 17 cytokines and 20 neurodegenerative biomarkers. Neuropsychological testing was performed to determine HAND staging via the Frascati criteria as normal, asymptomatic neurological impairment (ANI), mild neurocognitive disorder (MND) and HIV dementia (dem). We compared CSF profiles by CD4 group and neurocognitive status, adjusting for multiple comparisons. Results: Among 78 participants, 38 had CD4<200 with no active opportunistic infections, and 40 had moderate immunosuppression (CD4 351-500 cells/mcL). Neurocognitive function was found as normal (n=10), ANI (n=13), MND (n=33), and dementia (n=22). Persons with CD4<200 had significantly higher levels of several cytokines than those with CD4>350 (Table 1). Additionally, IL-2, IL-4, and MMP-1 were 100% detectable in CSF in persons with CD4<200 but detectable in 33%, 33%, 37%, respectively, among CD4>350 (P<0.001). IL5 was also more frequently detectable (76% vs. 33%, P=0.008). There was also lower levels of amyloid β 42 (P<.001) in persons with CD4<200. When comparing persons with normal or ANI function vs. MND or dementia, those with MND or dementia had higher geometric mean levels of IFN-G (7.4 pg/mL vs. 2.5 pg/mL; P=0.036) after adjusting for CD4.

Poster Abstracts

313

CROI 2015