CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

406 VITAMIN D IS NOT ASSOCIATED WITH HIV-ASSOCIATED NEUROCOGNITIVE DISORDER IN UGANDA Deanna Saylor 1 , Gertrude Nakigozi 2 , Noeline Nakasujja 3 , Kevin Robertson 4 , Ronald H. Gray 5 , Maria Wawer 5 , Ned Sacktor 1 1 Johns Hopkins Hospital, Baltimore, MD, USA, 2 Rakai Health Sciences Program, Kalisizo, Uganda, 3 Makerere University, Kampala, Uganda, 4 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 5 The Johns Hopkins University, Baltimore, MD, USA Background: The exact pathophysiologic mechanisms of HIV-associated neurocognitive disorder (HAND) are unknown. Increased deposition of amyloid- beta-42 (Aβ42) in the brain and altered Aβ42 metabolism leading to subsequent neuronal dysfunction have been proposed to contribute to the development of HAND. Vitamin D has been shown to suppress Aβ42 production and plaque aggregation in vitro. Vitamin D deficiency has been linked with an increased risk of Alzheimer Disease, which is also attributed to Aβ42 pathology. Therefore, we hypothesized that vitamin D deficiency may also contribute to the development of HAND. Methods: 399 HIV+ adults from the Rakai Community Cohort Study underwent a detailed neurological history and examination, comprehensive neurocognitive battery, functional status assessments, and peripheral blood draw at baseline. 333 (84%) underwent repeat assessment after 2 years. HAND stage was determined using Frascatti criteria and local normative data derived from 400 HIV- adults in Rakai. Baseline serum 25-hydroxy-vitamin D (25OH-D) was determined via LIAISON chemiluminescence assays, and vitamin D binding protein (VDBP) levels were determined using ELISA. 25OH-D levels were categorized as low (<20 ng/mL), sufficient (20 – 40 ng/mL), and optimal (>40 ng/mL). ANOVA was used to compare 25OH-D and VDBP levels by HAND status. Chi-square analyses were used to compare HAND status by 25OH-D category. Results: 53% of participants (n=211) were male, mean age was 35 (SD 8) years, and mean education was 5 (SD 3) years. All were antiretroviral therapy (ART) naïve at baseline, and 94% (n=312) were taking ART at follow-up. Mean 25OH-D level was 36 (SD 10) ng/mL with 63% of participants with sufficient levels, 33% with optimal levels, and 4%with low levels. Mean VDBP was 316 (SD 61) µg/mL. At baseline, 41% of participants had normal cognition, 6% had asymptomatic neurocognitive impairment (ANI), 38% had minor neurocognitive disorder (MND), and 15% had HIV-associated dementia (HAD). At follow-up, 48%were normal, 13% had ANI, 33% had MND, and 5% had HAD. Mean 25-OHD was not significantly associated with HAND status at baseline (Figure) or follow-up. HAND stage was not associated with vitamin D category. Mean VDBP did not vary by HAND stage at baseline or follow-up. Conclusion: Vitamin D status was not associated with HAND stage at baseline

405 HIV SUBTYPE AND RISK OF HIV-ASSOCIATED NEUROCOGNITIVE DISORDER IN RAKAI, UGANDA

Ned Sacktor 1 , Deanna Saylor 1 , Gertrude Nakigozi 2 , Kate Grabowski 1 , Noeline Nakasujja 3 , Xiangrong Kong 1 , Kevin Robertson 4 , Ronald H. Gray 1 , Maria Wawer 1 1 Johns Hopkins Hospital, Baltimore, MD, USA, 2 Rakai Health Sciences Program, Kalisizo, Uganda, 3 Makerere University, Kampala, Uganda, 4 University of North Carolina Chapel Hill, Chapel Hill, NC, USA Background: HIV-1 subtype B is predominant in the US while subtypes A, C and D predominate in Sub-Saharan Africa. The clade subtype may have an impact on HIV disease progression. Subtype D is associated with a more rapid CD4 cell count decline and faster disease progression compared to individuals with subtype A. Differences in co-receptor usage have been hypothesized to explain the differences in progression rates, as the probability of having an X4 virus was higher in subtype D infections than in subtype A infections. Previous studies also suggest that HIV subtype D is associated with an increased risk of HIV dementia (HAD) than subtype A among HIV+ individuals with advanced but not moderate immunosuppression. The objective of this study was to assess the association of HIV subtype with HIV-associated neurocognitive disorder (HAND) stage among HIV+ individuals with both moderate and advanced immunosuppression in rural Rakai, Uganda. Methods: 190 antiretroviral naïve HIV+ individuals with CD4 counts less than 200 and CD4 counts between 351-500 from the Rakai Community Cohort Study were evaluated by detailed neurological history, examination, neuropsychological tests and functional assessments and full length HIV sequencing on serum samples collected at baseline. HAND stage was determined using Frascati criteria. Subtype was determined by sequencing a portion of the gag and env regions. Results: HIV subtype frequency was D (24%, n=45), A (22%, n=42), D-A recombinant (31%, n=59), C (0.5%, n=1), other recombinants (22%, n=43). There was no difference in age between HIV+ individuals with subtype D (mean age= 35.2 years) and subtype A (mean age= 34.9 years). 67% of HIV+ individuals with subtype D had HAND, compared to 50%with subtype A (p=0.12) (see Figure). 60% of HIV+ individuals with subtype D had symptomatic HAND [mild neurocognitive disorder (MND)/ HAD], compared to 43%with subtype A (p=0.11). There was no association between the presence of HAD and HIV subtype (subtype D=13%, subtype A =12%, p=0.84). There were no differences between the presence of HIV subtype D vs. A and either HAND, symptomatic HAND, or HAD when stratified by CD4 counts. Conclusion: A trend was seen for an increased rate of either HAND or symptomatic HAND (MND/HAD) among HIV+ individuals with subtype D vs. A. However, HAD was not more common among HIV+ individuals with subtype D compared to those with subtype A. Additional analyses including results from the pol gene are on-going.

Poster Abstracts

or after two years of follow-up among HIV+ adults in Uganda. Vitamin D supplementation is unlikely to provide benefit in treating HAND in this population.

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