CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: ANRS143/NEAT001 is a randomised trial that showed non-inferiority over 96 weeks of ritonavir-boosted darunavir (DRV/r) + raltegravir (RAL) vs tenofovir difumarate/emtricitabine (TDF/FTC) in 805 ART naïve HIV-infected adults. We compared changes in whole blood telomere length (TL) in 201 randomly selected participants who had stored samples available (baseline and 96 weeks). We measured TL (telomere to single copy gene ratio) with monochrome quantitative multiplex PCR. Samples were tested in triplicate and those with a coefficient of variation > 0.10 were retested. We performed multivariable estimative analysis and predictive linear regression adjusted by baseline TL to elucidate predictive factors of TL change Results: Baseline characteristics of the 201 participants (104 RAL and 97 TDF/ FTC) did not differ from the whole parent trial population: 89%male, median age 39 years, Caucasian 83.6%, sexual transmission 93%, median duration of known HIV infection 2.1 years, HIV-1 RNA load 4.7 log 10 copies/mL, CD4 nadir/ baseline 300/324 cells/µL. Blood TL did not differ between groups at baseline (Table). At W96, participants receiving TDF/FTC had a statistically significant higher gain in TL than participants receiving RAL. Intragroup change at W96 was significant only in the TDF/FTC group (p<0.001). Difference in mean TL change between groups (TDF/FTC minus RAL) from baseline to W96 adjusted by baseline TL was 0.031 (p=0.009). This difference was not significantly confounded by baseline age, gender, known duration of HIV infection, CD4 (baseline/nadir), CD8 cells, CD4/CD8 ratio, HIV viral load (baseline/W96), smoking, alcohol use, statins or hepatitis C. These results were unchanged when TL was analysed as a binary variable (TL shortened/not shortened). In the predictive model the only variables associated with TL gain at W96 were treatment with TDF/FTC, younger age (mean difference 0.001, p=0.042) and no current use of alcohol at baseline (mean difference 0.048, p=0.038) Conclusion: This is the first clinical trial evaluating blood TL changes in naïve HIV participants starting ART. After 96 weeks participants receiving DRV/r + TDF/FTC had a significant higher gain in blood TL than those receiving DRV/r + RAL. The cause and clinical relevance of these differences between ART regimens are unknown and require further research. 759 THYMUS IS THE BAROMETER OF AGING IN HIV PATIENTS, ASSOCIATED WITH FRAILTY AND QOL Giovanni Guaraldi , Giulia Besutti, Andrea Malagoli, Iacopo Franconi, Nicoletta Riva, Alessandro Raimondi, Riccardo Scaglioni, Guido Ligabue, Marianna Menozzi, Antonella Santoro, Federica Carli, Stefano Zona, Vanni Borghi, Andrea Cossarizza, Cristina Mussini University of Modena and Reggio Emilia, Modena, Italy Background: Age related thymus decline impact inability of adults to restore immune function following HIV infection and leads to increased morbidity and frailty. We sought to investigate the relationship between thymus imaging detection and structural changes with immunometabolic markers, multi- morbidity, frailty, and quality of life (QoL) in men with HIV. Methods: This was a cross-sectional observational study including 665 consecutive HIV patients attending routine cardiovascular risk assessment with coronary artery calcium by mean of thoracic CT scan. Thymus detection and structural characteristics were retrospectively evaluated using a semiquantitative score based on the percentage of thymus solid tissue component (grade 0=no solid tissue; 1=1-25%; 2=26-50%; 3=51-75%; 4=76- 100%; 5=100% solid tissue). Frailty was measured with the frailty phenotype and a 37-item Frailty index. Results: 665 HIV infected patients (81%males), median age 53 years and median CD4=730/μL and HIV-RNA<40 c/mL in 98.5%were included. The table describes relevant immunometabolic markers. Thymus detection was also associated with lower prevalence of hypertension, diabetes, cardiovascular disease, MM, frailty and impaired QoL. In a multivariate logistic model, independent predictors for thymus detection were: male gender (OR=0.46, 0.22-0.93, p=0.03), BMI (OR=0.86, 0.81-0.98, p=0.03), IVDU (OR=0.22, 0.08-

0.52, p<0.01), Frailty (FI>=0.4) (OR=0.95, 0.92-0.99, p=0.02), HIV duration (residual after correction for age) (OR=0.8, 0.65-0.97, p=0.03) and impaired QoL (OR=2.5, 1.19-5.78, p=0.02) after correction by Age (years) (OR=1.15, 0.95-1.38, p=0.15). Given the association between thymus structural characteristics and age a secondary sensitivity analyses was performed matching all the thymus detected cases with a subset of age and sex matched thymus not detected controls from the same cohort (180 cases +180 controls) confirming association with frailty and QoL. The impact of thymus on frailty was confirmed including thymus structural changes as predictors of most frail individuals (FI>=0.4) in multivariate logistic regression (mild or higher, OR=0.3, 0.12-0.93, p = 0.04) after correction for HIV duration (residual) (OR=1.10, 1.02-1.20, p=0.01), CD4/ CD8 (OR=1.4, 0.6-3.3, p=0.38) and HIV late presentation (OR=0.5, 0.19-1.4, p=0.18) Conclusion: Thymus detection and structural changes are associated with immunometabolic disarrangements and clinical spectrum of aging in HIV patients.

Poster Abstracts

760 METHAMPHETAMINE USE INDEPENDENTLY PREDICTS PREMATURE AGING IN HIV+ INDIVIDUALS Sanjay R. Mehta 1 , Jennifer Iudicello 1 , Ronald J. Ellis 1 , Jue Lin 2 , Erin Morgan 1 , Debralee Cookson 1 , Robert K. Heaton 1 , Igor Grant 1 , Scott L. Letendre 1 1 University of California San Diego, La Jolla, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: As HIV+ adults grow older, aging-related comorbidities occur more frequently than in age-matched controls. Little is known about the role of substance use, which is common in this population, in this “premature” aging process. We examined the effects of methamphetamine (METH) dependence and HIV on physiologic and functional measures of aging. Methods: Using clinical, demographic and laboratory measures obtained from 124 participants (HIV-/METH- n=31, HIV-/METH+ n=24, HIV+/METH- n=35, HIV+/METH+ n=34), we examined the impact of HIV serostatus and METH dependence in relation to epigenetic changes (telomere to single copy gene ratio [T/S], mitochondrial DNA [mtDNA] level, and relative abundance of the mitochondrial common deletion within the mtDNA population [RACD]) as well as to functional status, cardiovascular comorbidity (Framingham risk scores), renal functional changes, and age-related anthropometric (hip/waist ratio) changes. Results: Controlling for age, HIV was associated with a lower Karnofsky rating (p<0.001), a larger hip/waist ratio (p=0.052), higher creatinine (p=0.002), and shorter T/S ratio (p=0.003). Similarly, controlling for age, METH use was associated with a shorter T/S ratio (p=0.002) but a lower creatinine (p=0.029). In multivariate regression including HIV, METH, and age, both METH+ and HIV+ remained significant predictors of shorter T/S ratios. In this model and within our study cohort, a 40-year-old HIV+/METH+ individual had a T/S ratio equivalent to a 44.5-year-old HIV+/METH-, a 45.2-year-old HIV-/METH+, and a 60.7-year-old HIV-/METH- individual. When examining RACD, another epigenetic marker of aging, METH+ participants had significantly smaller RACD (p=0.034) only in the HIV seronegative group. In a multivariate regression of creatinine adjusting for age and body mass index, both HIV and METH remained statistically significant, while tenofovir exposure was not a predictor of creatinine level.

CROI 2018 284