CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

403 AGE-ASSOCIATED DEMENTIA AMONG OLDER PEOPLE WITH HIV IN THE US: A MODEL-BASED ANALYSIS Emily P. Hyle 1 , Julia H. Foote 1 , Shibani S. Mukerji 1 , Keri N. Althoff 2 , Paul E. Sax 3 , Krishna P. Reddy 1 , Liyang Yu 1 , Leah H. Rubin 4 , Kenneth Freedberg 1 , Milton C. Weinstein 5 , Anand Viswanathan 1 , Lee H. Schwamm 1 , Fatma Shebl 1 , Rochelle P. Walensky 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 Brigham and Women's Hospital, Boston, MA, USA, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: Approximately 25-30% of people with HIV (PWH) in the US (~300,000) are ≥55y and at risk for age-associated dementias (AAD), including Alzheimer’s disease and vascular dementias. We project the lifetime cumulative incidence and mortality associated with AAD among PWH in the US. Methods: We expanded the validated Cost-effectiveness of Preventing AIDS Complications (CEPAC) model to incorporate age- and sex-stratified risk of AAD with increased mortality among those who develop AAD. We first validated the model in the general population (age, mean±SD [62y±6]). Next, we simulated a population of people at high risk for HIV acquisition given risk behaviors, so mortality is adjusted by a relative mortality rate (RMR) for MSM, IDU, and socio-economic status. We then simulated the 2015 US population of people ≥55y diagnosed with HIV (CD4, mean±SD [490/μL±209]) of whom 73% are in care and 63% are virologically suppressed. Loss to follow-up (LTFU) is 13%/year, and mortality is due to HIV, AAD, and RMR-adjusted other causes. We estimated AAD prevalence, AAD incidence, and AAD-associated mortality using published data from populations without HIV. Model outcomes included AAD cumulative lifetime incidence and life expectancy (LE). We performed sensitivity analysis on HIV-specific (e.g., LTFU) and AAD-specific (e.g., AAD incidence) parameters, as well as the impact of a 5y forward-shift in AAD incidence and non-HIV- associated mortality (i.e., premature aging). Results: Among older males/females with HIV, we projected AAD cumulative incidence of 18%/17% and LE of 14.5y/14.6y, compared to higher cumulative incidence and longer LE among people at high risk for HIV or in the general population (Table). Without LTFU, AAD cumulative incidence and LE increased among PWH because competing HIV-related mortality was reduced. If PWH experienced premature aging, AAD cumulative incidence increased with decreased LE. If AAD incidence among PWH was 2x that of the population without HIV, then AAD cumulative incidence increased but with a smaller impact on life expectancy. Limitations included uncertain estimates of AAD incidence and AAD-associated mortality among PWH. Conclusion: Using current data and a validated simulation model, we project that almost 20% of PWH now ≥55y in the US are likely to develop AAD over their lifetime. Cumulative incidence of AAD will be greater if the competing risk of mortality from HIV is reduced or if the risk of AAD is higher among PWH than among those without HIV.

Methods: We performed a single center, randomised, open, controlled trial in Gothenburg, Sweden. Neuroasymptomatic PLHIV with stable antiretroviral therapy (ART) for >12 months and with HIV RNA <50 copies/mL who consented to participate in the study were screened. Individuals who had plasma homocysteine >12 µmol/L were eligible for the study. Patients were randomised to either treatment with Triobe (cyanocobalamin 0,5 mg, folic acid 0,8 mg, and pyridoxine 3 mg) or to no treatment for 12 months. Results: One hundred and twenty-four PLHIV matching the inclusionciteria were screened for p-homocysteine levels. There was a significant correlation between p-homocysteine levels and p-NFL levels at screening (r = 0.62, p <0.0001). Sixty-one patients were randomised to either treatment with Triobe (n = 31) or to no treatment (n = 30). P-homocysteine levels decreased from a median of 15.9 (interquartile range (IQR) 13. 5–17.2) to 9.9 (IQR 8.5–11.4) (p < 0001) between baseline and month 12 in the B-vitamin arm, but not in controls: 14.6 (IQR 13.4–16.9) and 16 (IQR 13.9–18) at baseline and month 12, respectively. At baseline, median plasma NFL was 12.6 (IQR 8.8–21.1) pmol/L in the B-vitamin arm and 10.2 (IQR 8.02–14.9) in the control arm. The levels did not change significantly to month 12 in either arm, 13.8 (IQR 10.3-18.8) and 12.8 (IQR 8.4–14.7) pmol/L, respectively. Conclusion: We found a significant correlation between p-homocysteine and p-NFL levels in neuroasymptomatic PLHIV on ART. B-vitamin substitution for 12 months had no effect on p-NFL. The mechanism behind the correlation between homocysteine and NFL at baseline, also seen in the earlier study, is unknown and needs to be further investigated. The study will continue until 24 months of follow-up. 405 CONSERVED CSF HIV ANTIBODY RESPONSE IN PATIENTS WITH DIVERSE NEUROLOGIC PHENOTYPES Isobel A. Hawes 1 , Ryan Schubert 1 , Akshaya Ramesh 1 , Gavin Sowa 1 , Joanna Hellmuth 1 , Magnus Gisslén 2 , Richard W. Price 1 , Michael Wilson 1 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Gothenburg, Gothenburg, Sweden Background: The CNS is exposed to HIV during primary infection and likely continuously during untreated chronic infection. ART that suppresses plasma HIV RNA also usually suppresses CSF HIV RNA with occasional asymptomatic episodes of detectable HIV RNA. A rare exception is development of neurosymptomatic (NS) CSF escape in which CNS HIV infection develops despite plasma viral suppression. While drug resistance and incomplete drug penetration predispose to this, the origins of NS escape are not fully understood. Methods: To assess whether NS escape might be triggered by an unidentified CNS pathogen and/or whether the CSF anti-HIV antibody repertoire might distinguish NS escape, CSF was collected from 25 HIV-infected participants, some longitudinally, with diverse neurologic phenotypes and treatment status (Table 1). CSF samples were incubated with a VirScan T7 bacteriophage library expressing 481,966 peptides tiled across all known vertebrate and arbovirus genomes that previously identified CSF enteroviral antibodies in pediatric acute flaccid myelitis. Antibody-bound phage were immunoprecipitated and after two rounds of enrichment, were deep sequenced to quantify enriched viral peptides. Separately, unbiased metagenomic next-generation sequencing (mNGS) of total CSF RNA was performed to look for unidentified infections and HIV. Results: mNGS was 100% concordant with HIV RNA PCR for samples with 530 viral copies (n=15) and 0% concordant from samples with £ 113 viral copies (n=8). In addition, mNGS detected the two known infections in the secondary escape patients. Additionally, the CSF anti-HIV antibody repertoire primarily enriched two distinct epitopes within the HIV envelope (env) protein in the VirScan assay, regardless of neurologic or treatment status. These epitopes mapped to the V3 loop near the binding site for CCR5 and to the C-terminal heptad repeat domain. Conclusion: CSF mNGS did not identify additional infections in HIV NS escape. Preliminary VirScan data suggest that immunodominant epitopes in the CNS are highly conserved across patients, regardless of neurologic status. However, compared to similar epitopes described in sera, we identified CSF antibodies specific for the R306S mutation in the gp120 V3 region which has been associated with brain-derived env sequences and increased macrophage tropism.

Poster Abstracts

404 A RANDOMISED CONTROLLED TRIAL ON THE EFFECT OF B VITAMINS ON NEURONAL INJURY IN PLHIV Erika Ahlgren 1 , Lars Hagberg 1 , Lars-Magnus Andersson 1 , Aylin Yilmaz 1 , Åsa Mellgren 1 , Kaj Blennow 1 , Henrik Zetterberg 1 , Magnus Gisslén 1 1 Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Background: We have previously found an association between plasma homocysteine levels and cerebrospinalfluid neurofilament light protein (NFL) –a marker of neuronal injury– in people living with HIV (PLHIV). Elevated levels of homocysteine is an indicator of B12 and/or folate deficiency. The aim of this study was to investigate if B-vitamin substitution would lead to decreased levels of plasma NFL.

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