CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

421 ORAL MGBG WITH cART BLOCKS AIDS AND SIVE, AND REDUCES CNS INFECTION AND CAROTID IMT Jaclyn Mallard 1 , Jamie Schafer 1 , Kevin White 1 , Arianna Noggle 1 , Joseph Enders 1 , Cecily Midkiff 2 , Xavier Alvarez 2 , Tricia H. Burdo 3 , Kenneth C. Williams 1 1 Boston College, Chestnut Hill, MA, USA, 2 Tulane National Primate Research Center, Covington, LA, USA, 3 Temple University, Philadelphia, PA, USA combined antiretroviral therapy (cART). Activated monocytes, and brain and cardiovascular macrophages remain despite cART. In this study, we use oral administration of methylglyoxal-Bis-Guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor targeting myeloid cells, with cART, as an adjunctive therapy targeting activated Mo/MΦ. Methods: Three cohorts of CD8-depleted, SIVmac251-infected Rhesus macaques were used: untreated animals (n = 4), animals that received daily cART (n = 6) at 21 days post infection (dpi) and animals that received daily MGBG+cART (n = 5) at 21 dpi. Treated animals were time-sacrificed at 120 dpi and untreated animals were sacrificed with development of AIDS. Results: None of the cART or MGBG+cART animals developed AIDS or SIV- associated encephalitis (SIVE), but 3/6 cART alone animals had meningitis, compared to 0/6 MGBG+cART animals. MGBG+cART animals had a significant decrease in MFI of CX3CR1 (p<.01) and CD163 (p<.01) on CD14+CD16+ monocytes compared to controls. At necropsy, percentages of BrdU+ CD14+CD16+monocytes were significantly lower in MGBG+cART animals (0.4%) compared to cART alone (3.6%) and control animals (23.2%) (p<.05). MGBG+cART resulted in an additive 1.5 fold decrease in the percentage of CD14+CD16+monocytes compared to control animals vs cART alone (p<.01). MGBG+cART resulted in a 2.5-fold decrease in MFI of CD169 on CD14+CD16+ monocytes compared to cART alone (p<.0001). Plasma viral load of cART vs MGBG+cART was equivalent, and at least 4.5 log less than controls. There was a 10-fold decrease in the number of SIVp28+ cells in the CNS of MGBG+cART animals vs cART alone (p <.05). There was a trend of lower numbers of macrophages in the brains of MGBG+cART animals (23.6+5.5 cells/mm2) compared to cART animals (31.0+4.9 cells/mm2). There were no significant differences between the number of macrophages in left ventricles with MGBG+cART vs cART alone. There was a significant difference between control cIMT vs MGBG+cART (p<.05) and control cIMT vs cART alone (p<.05). Conclusion: These results demonstrate an additive effect of MGBG+cART targeting activated monocytes and activated, infected CNS macrophages, in addition to blocking AIDS and SIVE and decreasing cIMT. These results point to MGBG that can be used in addition to cART that can function as an adjunctive therapy targeting HIV associated co-morbidities. 422 DEPRESSION IS COMMON AND ASSOCIATED WITH COGNITIVE FUNCTION IN WELL-TREATED HIV Åsa Mellgren 1 , Maria Jivegård 1 , Magnus Gisslén 2 1 South Älvsborgs Hospital, Boras, Sweden, 2 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Background: Depression and depressive symptoms are common persons with HIV (PWH) and is often underdiagnosed. Neuroinflammation has been suggested to contribute to the high prevalence of depression but there is very limited data on CSF biomarkers and its relation to depressive symptoms in HIV. We wanted to investigate the association between CSF immune activation, depressive symptoms and neurocognitive function. Methods: We have prospectively included PWH in a longitudinal study of CSF biomarkers, depressive symptoms and neurocognitive performance. Depressive symptoms were assessed by Montgomery Åsberg Depression Rating Scale (MADRS) where a score >12 was used as cut-off for depression. CSF was analyzed for HIV RNA, white blood cell count, neurofilament light protein (NFL) β2-microglobulin, neopterin, IgG and albumin. Serum and plasma was sampled for HIV RNA, CD4 cell count, albumin, IgG, neopterin and β2-microglobulin. Neurocognitive function was assessed in five cognitive domains by CogState Brief Battery and Groton Maze Learning Test. Patients responded to screening questions regarding cognitive function recommended by EACS. All subjects had been on ART for >6 months (mean 9.7 years +/- 6.7). 51 male and 26 female were included. Mean age was 50 (+/-11.6) years. Statistical method The association between MADRS ≤12 vs >12, and selected patient characteristics, laboratory data and CogState variables were performed by using generalized estimating equation (GEE) models for binary outcome, with log-link function, Background: HIV-associated neurocognitive disorders (HAND) and cardiovascular disease persist despite stable viral suppression with

allowing for repeated measures and adjustment for within-patient correlations. All tests were two-tailed and conducted at 0.05 significance level. Results: 20 % of individuals scored >12 on MADRS depression score. Depressive symptoms were significantly associated with impaired neurocognitive functioning (Combined CogState score of five tests) (RR=1.8, p<0.001), and to responding “yes” on all three screening questions (RR from 5.1-22.0, p<0.01). No significant association was found between depressive symptoms and plasma or CSF inflammatory markers, CSF NFL, HIV RNA or CD4 cell count (nadir or current). Conclusion: We found no association between CSF immune-activation and depressive symptoms in well-treated PWH. Instead, a there was significant association between depression and neurocognitive impairment both by subjective measures and CogState neurocognitive testing of five cognitive domains. It is important to screen for depression in patients with neurocognitive symptoms. 423 DEPRESSION SYMPTOM CHANGES OF HIV POSITIVE INDIVIDUALS IN THE RAKAI COHORT Noeline Nakasujja 1 , Gertrude Nakigozi 2 , Deanna Saylor 3 , Kevin Robertson 4 , Ronald H. Gray 3 , Maria Wawer 3 , Ned Sacktor 3 1 Makerere University College of Health Sciences, Kampala, Uganda, 2 Rakai Health Sciences Program, Kalisizo, Uganda, 3 Johns Hopkins University, Baltimore, MD, USA, 4 University of North Carolina Chapel Hill, Chapel Hill, NC, USA Background: Immunological function can impact the expression of depression symptoms but has not been well studied, especially in Sub Saharan Africa which has two thirds of the global burden of HIV infection. In this setting only half of HIV+ have access to antiretroviral therapy. Depression, the most common neuropsychiatric disorder in the HIV population is associated with initial HIV diagnosis, the effect of a chronic illness and stigma. We evaluated the effect of baseline immunological status( CD4 and viral load) on the expression of depressive symptoms in a cohort of HIV positive individuals followed up for 2 years Methods: We evaluated 333 antiretroviral naïve HIV+ (150 with CD4 count < 200cells/µL; 183 with CD4 351-500 cells/µL) at baseline and 2 years after initiation of antiretroviral therapy (ART). Significant depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale (CESD) with a cut off score of >16. Viral load was measured using Abbot Realtime assay. Odds ratios with 95% CI were estimated using logistic regression. Results: The mean (SD) age was 35.3 (8.6) years. There were more females 102 (56%) within the CD4 range 350-500 µL. Viral load was >1000 copies in 311 (93.9%) of ART naive participants at baseline and 35 (10.5%) at follow up. By the time of follow up, 312(93%) of the participants had initiated ART. The CESD mean (SD) score was higher at baseline 9.6 (9.3) than at the 2 year follow up 4.4 (7.4) p<0.01, see figure 1. There were 73(22%) individuals with CESD >16 at baseline and 28(8.4%) at follow up. Women had a higher mean CESD score than men both at baseline (10.8 vs 8.4) p<0.01 and follow up (5.2 vs 3.6) p<0.01. Adjusted odds for having significant depressive symptoms (CESD >16) were lower at follow up OR =0.3, 95%CI 0.2-0.5; p<0.01, and if baseline CD4 was 350-500 cells/µL, OR = 0.6, 95%CI 0.3-0.9;p= 0.03. Depression risk was higher for women than men OR = 1.6, 95%CI ;1.1-2.5; p=0.02, and increasing age OR =0.1, 95%CI 1.00-1.05; p=0.01. Viral load was not associated with depression symptoms at baseline and follow up. Conclusion: Depressive symptoms lessen but persist even when the immunological function improves in HIV patients after initiation of ART. Females have more depressive symptoms than males. Managing depression in HIV infected patients should form part of routine HIV care.

Poster Abstracts

CROI 2018 149