CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

448 CSF AND BLOOD HIV RNA RELATIONSHIP IN ACUTE HIV IS LINKED TO CD4/CD8 RATIO Phillip Chan 1 , Payal Patel 2 , Joanna Hellmuth 3 , Donn Colby 1 , Eugène Kroon 1 , Carlo Sacdalan 1 , James L. Fletcher 1 , Suteeraporn Pinyakorn 4 , Linda Jagodzinski 5 , Shelly J. Krebs 5 , Nelson L. Michael 5 , Jintanat Ananworanich 4 , Victor Valcour 3 , Serena S. Spudich 2 1 SEARCH, Bangkok, Thailand, 2 Yale University, New Haven, CT, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 US Military HIV Research Program, Bethesda, MD, USA, 5 US Military HIV Research Program, Silver Spring, MD, USA Background: HIV RNA levels in the systemic circulation and cerebrospinal fluid (CSF) are closely linked in chronic infection with a relationship modified by the degree of immunosuppression and presence of central nervous system (CNS) opportunistic infections or HIV encephalitis. Examination of this relationship during acute HIV infection (AHI) offers a unique opportunity to explore determinants of viral entry into the CNS and may be essential in deciphering origins of HIV CNS compartmentalization and the development of neurologic complications. Methods: We examined pre-antiretroviral therapy baseline data in the RV254/ SEARCH010 Thai AHI cohort to identify factors that correlate to CSF HIV RNA level and the degree of CNS invasion relative to blood, quantified by the difference between plasma and CSF HIV RNA level (Log 10 plasma HIV RNA - Log 10 CSF HIV RNA = PCdiff). Plasma and CSF HIV RNA levels across the Fiebig stages were explored and CSF immune markers were compared in a subset of participants in relation to their PCdiff status. Results: From Apr 2009 to Dec 2016, 117/430 enrollees underwent lumbar puncture (97%male, median age 27 (IQR 23-32) years, and median duration of infection 18 (IQR 14-23) days). 43 (37%) presented at Fiebig stage I or II. 27 (23%) had HIV RNA levels below the level of quantification (80 copies/ml). Among those with a quantifiable level (n=90), the median CSF HIV RNA level and PCdiff were 3.76 (IQR 2.81-4.82) and 2.36 (range 0.10-4.40) log 10 copies respectively. Median HIV RNA level was highest during Fiebig III in plasma (6.49 log 10 copies) and Fiebig IV in CSF (4.41 log 10 copies). In a multivariate linear regression model, plasma HIV RNA level and CD4/CD8 ratio correlated with CSF HIV RNA level (p<0.001) with adjusted β coefficient of 0.604 and -0.616, respectively. CD4/CD8 ratio was the only correlating factor of PCdiff (p=0.018, adjusted β coefficient = 0.380). Seven participants had a small PCdiff below 1 log 10 (Figure). Compared to others with quantifiable CSF HIV RNA, they had statistically higher levels of CSF neopterin (p=0.030), sCD163 (p=0.006), IL-6 (p=0.031) and sCD14 (p=0.011). Conclusion: In AHI, CSF HIV RNA level correlates with that in plasma and associates with heightened CNS immune activation, and PCdiff is larger in AHI than in chronic infection. Higher CD4/CD8 ratio independently correlates with lower CSF HIV RNA level and higher PCdiff, suggesting a protective role of systemic immune preservation in limiting HIV entry into the CNS.

447 RISK AND PREDICTORS OF ASYMPTOMATIC AND SYMPTOMATIC CSF VIRAL ESCAPE IN HIV+ PATIENTS Carmela Pinnetti , Patrizia Lorenzini, Ilaria Mastrorosa, Valentina Fedele, Stefania Carta, Alessandra Vergori, Alberto Giannetti, Massimo Tempestilli, Adriana Ammassari, Susanna Grisetti, Francesco Baldini, Chiara Agrati, Maria R. Capobianchi, Carlo F. Perno, Andrea Antinori Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy Background: Symptomatic CSF viral escape (sCVE) has been associated with an independent replication and evolution of resistance in the CNS, whereas asymptomatic CVE (aCVE) could be the result of cells trafficking or it may be an occasional “blip”. Aimwas to estimate the risk and identify the predictors of aCVE and sCVE in HIV+ patients (pts). Methods: Single-centre, retrospective study on CSF/plasma pairs from HIV+ pts with and without neurologic signs and symptoms undergoing lumbar puncture (LP) for diagnostic or therapeutic reasons. CVE was defined as: a) detectable CSF HIV-RNA with concurrent plasma <50 cp/mL; b) CSF HIV-RNA >1.0 log 10 higher than (aCVE) or 2x (sCVE) concomitant plasma. Impaired Blood Brain Barrier (BBB) was defined by CSF/plasma albumin quotient x 103 (Qalb) higher than age-normalized reference threshold. Variables analyzed: gender, age, HIV transmission mode, CDC stage C, duration of HIV infection and of antiretroviral exposure, CD4 at nadir and at LP, HCV coinfection, CPE score, cells and proteins in CSF, CSF neopterin, CSF NFL, CSF sCD14, BEE dysfunction, calendar year of LP. Adjusted ORs of CVE were calculated by fitting a multivariable logistic regression model. Results: 624 CSF/plasma paired samples from 322 pts, collected between 1999 and 2014, were included. At LP, 82.5% of pts were male, median age 46y (IQR, 40-51), and HIV transmission: 39.7% heterosexual, 22%MSM, 28.8% IDU. Among samples, CD4 nadir was <200/mm 3 in 59.3%, CDC stage C in 87.8%. CSF was collected in 18% in 1999-2004, 33.3% in 2005-2009, and 48.7% in 2010- 2014. At LP, 59% of samples had HIV-RNA <50 cp/mL in plasma and a median CD4 of 178/mm 3 (IQR, 79-362). aCVE was observed in 29 samples (4.6%), sCVE in 22 (3.2%). At multivariable analysis, older age, CD4 nadir <200 and less recent calendar period were associated with an increased risk of aCVE. In a subgroup of 153 samples from pts with available Qalb, BBB dysfunction was associated with 5.6 fold higher risk of aCVE. Otherwise, only female gender and increased number of cells in CSF were found associated with higher probability of sCVE (Tab.1). Conclusion: In this large paired CSF/plasma sample collection, aCVE and sCVE were found with a low prevalence. aCVE, which was less frequent in more recent years, was predicted by immunological status at LP and BBB damage. Conversely, sCVE was associated with higher CSF pleiocytosis, suggesting that an inflammatory response against HIV-1 may be implicated in the pathogenesis of this disorder.

Poster Abstracts

CROI 2018 159