CROI 2019 Abstract eBook
Results: Individuals in this cohort had moderate CD4+ T cell counts (median=356 cells/µl) and CSF viral loads (median=38,905 RNA cp/ml). HIV-1 subtype frequency was A (33%), D (19%), A-D recombinants (33%), A-C recombinants (5%), and other recombinants (10%). HAND stage frequency was: 36% normal cognition, 8%with asymptomatic neuropsychological impairment, 34%with mild neurocognitive disorder, and 22%with HAD. 64% of individuals had CSF compartmentalization. There was a trend for compartmentalization to be associated with impaired cognition (p=0.37, figure 1) and compartmentalization was a significant predictor of impaired verbal fluency (p=0.006). Conclusion: A cohort of HIV+ individuals with subtypes A, D, and recombinants was observed to have a very high rate of CSF compartmentalization. This rate exceeds our previous estimate for a similar cohort of individuals infected with subtype B HIV-1, suggesting that subtypes A and/or D may colonize and establish replicating populations in the CNS more readily than subtype B variants. High rates of compartmentalization may impact long-term neurocognitive performance in this cohort.
Results: 187 participants had paired blood and CSF sampling in at least one visit at baseline, week 24, or week 96. The participants were 97%male (182/187) with median age 26 years and baseline Fiebig stage 3 (83/186, 45%), CD4 count 388 cells/mm3, and plasma HIV RNA 5.84 log10 copies/mL. ART was started at a median of 19 days post estimated infection. At baseline, 126/149 participants (85%) had quantifiable CSF HIV RNA (median 3.15 log10 copies/mL). At week 24 (n=89), four participants (4%) had quantifiable CSF HIV RNA, with one case of CSF escape identified with plasma HIV RNA < 50 copies/ml and CSF HIV RNA 2.50 log10 copies/mL. At week 96 (n=46), one participant (2%) had quantifiable CSF HIV RNA, which did not meet criteria for CSF escape. All other cases of quantifiable CSF HIV RNA were due to ART failure. The participant with CSF escape was treated with efavirenz/tenofovir/lamivudine and had a CD4 count of 840 cells/mm3 and CSF WBC and CSF protein of 4 cells/mm3 and 30 mg/dL. His MRI at week 24 showed a small nonspecific T2/FLAIR hyperintense focus in the right high frontal white matter. He did not have a lumbar puncture performed at baseline nor at subsequent visits. Conclusion: While levels of CSF HIV RNA in untreated AHI are high, initiating treatment during AHI results in a very low rate of CSF escape in the first two years of ART. The low rate of CSF escape may also be impacted by high levels of adherence to ART in this cohort or the short duration of ART. Longitudinal monitoring will be required to verify if CSF escape remains rare under long-term ART in early treated individuals.
451 TREATMENT REGIMENS FOR MANAGING SYMPTOMATIC CSF HIV ESCAPE IN PUNE, INDIA Ameet N. Dravid 1 , Raviraj Gawali 1 , Mahenderkumar Medisetty 1 , Kartik Natarajan 1 , Chinmay Saraf 2 , Milind Kulkarni 3 , Sachin Kore 4 , Niranjan Rathod 5 , Umakant Mahajan 6 , Andrea Calcagno 7 1 Poona Hospital and Research Centre, Pune, India, 2 Precision Diagnostics and Biosciences, Pune, India, 3 Ruby Hall Clinic, Pune, India, 4 Ashwini Sahakari Rugnalaya, Pune, India, 5 Apex Hospital, Kolhapur, India, 6 geneOmbio Technologies Pvt Ltd., Pune, India, 7 University of Torin, Torino, Italy Background: Symptomatic CSF HIV escape(sCVE) in limited resource countries(LRCs) has been reported in patients on 2nd line protease inhibitor(PI) based ART. Management includes performing CSF and plasma genotypic resistance testing(GRT) and changing ART accordingly; however GRT is not routinely available in LRCs. Hence ART optimization is done by including drugs with excellent CNS penetration like Zidovudine(AZT intensification) or shifting to a new PI and Integrase inhibitor(PI/INSTI intensification). Methods: In this retrospective cohort study conducted between 1st March 2009 and 1st March 2018, we included patients developing sCVE on 2nd line PI-based ART. sCVE was defined as either a)detectable CSF viral load(VL >20 copies/ml) with undetectable plasma VL or b)CSF VL ≥0.5 log10 higher than plasma VL. Individuals in whom GRT could not be performed or drug resistance mutations(DRM) could not be identified were prescribed AZT intensification to current ART(Group 1).Those patients demonstrating DRM on GRT or already taking AZT as part of PI based ART or having history of AZT toxicity were shifted to a new PI,INSTI +/- Maraviroc(Group 2). Plasma and CSF VL was repeated after 6 months of ART modification. Results: 41 patients with sCVE were identified: 20 in Group 1 and 21 in Group 2. Baseline characteristics in both groups are shown in Table 1. After AZT intensification there was complete resolution of symptoms in 17(85%) patients.
450 MINIMAL INCIDENCE OF CSF ESCAPE AFTER INITIATION OF ART IN ACUTE HIV INFECTION Ryan C. Handoko 1 , Phillip Chan 2 , Linda Jagodzinski 3 , Suteeraporn Pinyakorn 4 , Nittaya Phanuphak 2 , Carlo Sacdalan 2 , Eugène Kroon 2 , Chutharat Munkong 2 , Netsiri Dumrongpisutikul 5 , Robert J. O’Connell 6 , Robert Gramzinski 3 , Victor Valcour 7 , Jintanat Ananworanich 3 , Serena S. Spudich 1 , for the SEARCH 010/RV254 Study Team 1 Yale University, New Haven, CT, USA, 2 SEARCH, Bangkok, Thailand, 3 US Military HIV Research Program, Silver Spring, MD, USA, 4 Henry M Jackson Foundation, Bethesda, MD, USA, 5 Chulalongkorn University, Bangkok, Thailand, 6 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 7 University of California San Francisco, San Francisco, CA, USA Background: Despite suppression of HIV viral replication in the periphery by antiretroviral therapy (ART), up to 10% of treated individuals have quantifiable HIV in the CSF, termed CSF escape. CSF escape may be asymptomatic but has also been linked to progressive neurological disease. CSF escape has not yet been assessed after initiation of ART during acute HIV infection (AHI). Methods: Thai AHI participants underwent blood sampling and optional cerebrospinal fluid (CSF) sampling at baseline followed by immediate ART, and then longitudinally at weeks 24 and 96. HIV RNA was quantified using Roche Amplicor and COBAS TaqMan assays with a lower limit of quantitation of 20-50 copies/mL in plasma and 80 copies/mL in CSF. Participants with quantifiable CSF HIV RNA and plasma HIV RNA less than 50 copies/mL or CSF HIV RNA greater than 1-log higher than plasma HIV RNA during ART were identified as cases of CSF escape.
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