CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Conclusion: In subjects starting an initial therapy or a switch regimen with an undetectable plasma HIV-1-RNA, there are no significant differences in the D/C rates due to AEs among those receiving DTG, RAL or EVG/c. For those receiving DTG, there are no significant differences between those receiving ABC/3TC or TDF/FTC. Marginal structural models adjusted for baseline and time-varying confounding variables will be run in further analysis. 652 IMPACT OF TENOFOVIR DIFUMARATE ON TELOMERE LENGTH OF AVIREMIC HIV-INFECTED PATIENTS Rocio Montejano 1 , Natalia Stella-Ascariz 1 , Susana Monge 2 , Jose I. Bernardino 1 , Ignacio Pérez-Valero 1 , Laura Pintado 3 , Marisa Montes 1 , Jesus Mingorance 1 , Rosario Perona 3 , Jose R. Arribas 1 1 Inst de Investigación Hosp Univ La Paz, Madrid, Spain, 2 Univ de Alcalá de Henares, Madrid, Spain, 3 Inst of Biomed Rsr “Alberto Sols,” Madrid, Spain Background: In vitro tenofovir is a potent inhibitor of human telomerase (J Inf Dis 2013; 207:1157, J Acquir Immune Defic Syndr 20 August 2016. doi:10.1097/ QAI.0000000000001154). The in vivo relevance of this inhibition is unknown. Methods: Cross sectional study of HIV-1 infected patients with suppressed virological replication (HIV-1 RNA < 50 copies/mL for > 1 year). Telomere length (TL) was measured in whole blood by monochrome quantitative multiplex PCR assay. All samples were run in triplicate. We performed a multivariate analysis to elucidate factors associated with TL and also evaluated the association between TL and the use of tenofovir difumarate (TDF) adjusted by significant confounders. Results: 200 patients were included: 72%male, median age 49 IQR (45-54.5) years; median time on ART 14.9 years (10.28-17.92), on NRTIs 11.9 (9.01-16.16) years, and with virologic suppression 6.8 years (4.56-7.68); median current CD4 776 cells/μL (551-1037); 64% currently receiving triple therapy, 32.5% ritonavir-boosted protease inhibitor monotherapy and 3.5% other NRTI-sparing regimen. 103 patients had exposure to TDF (median time 8.5 years (3.88-10.37), 69.9%>5 years) and 97 were never exposed to TDF. In the univariate analysis (Figure 1) TL was not associated with duration of TDF exposure; compared to patients with <5 years of TDF-exposure, those with TDF-exposure for 5-10 years had 8.7% longer TL (p=0.060) and those with >10 years of exposure had 6.4% longer TL (p=0.189). In contrast, Caucasian race, older age, smoking, time with known HIV infection, time receiving ART and time on NRTI were significantly associated with shorter TL. In the multivariate analysis significant predictors of shorter TL were: older age ≥50 years (p=0.008), parental age at birth (p=0.038), Caucasian race (p=0.048) and longer time of known HIV infection (known infection for 10-20 years and ≥20 years compared with <10 years, p=0.003 and p=0.056 respectively). There was no association between TDF exposure and TL after adjusting for possible confounding factors (age, parental age at birth, race and time of HIV infection). Total time receiving ART and duration of treatment with NRTIs were associated with shorter TL but these associations were explained by time of known HIV infection. Conclusion: Our data do not suggest that telomerase activity inhibition caused by TDF in vitro, leads to telomere shortening in peripheral blood of HIV infected patients. 653 DARUNAVIR/R USE AND INCIDENT CHRONIC KIDNEY DISEASE IN HIV-POSITIVE PERSONS Lene Ryom 1 , Jens D. Lundgren 1 , Peter Reiss 2 , Ole Kirk 1 , Matthew Law 3 , Michael Ross 4 , Philippe Morlat 5 , Christoph A. Fux 6 , Amanda Mocroft 7 , for the D:A:D Study Group 1 CHIP, Rigshosp, Copenhagen, Denmark, 2 Stichting HIV Monitoring and Academic Med Cntr Amsterdam, Amsterdam, Netherlands, 3 Kirby Inst, Sydney, Australia, 4 Mt Sinai Sch of Med, New York, NY, USA, 5 CHU Bordeaux, Bordeaux, France, 6 Clinic for Infectious Diseases and Hosp Hygiene, Kantonsspital Aarau, Aarau, Switzerland, 7 Univ Coll London, London, UK Background: Prior studies have linked exposure to protease inhibitors (PIs) with excess risk of chronic kidney disease (CKD). Whether such safety signals remain for more contemporary PIs, such as darunavir (DRV/r), remains unclear. Methods: D:A:D participants with >3 estimated glomerular filtration rate (eGFR) measurements, were followed from their first eGFR>60 mL/min/1.73m 2 after 1.1.2009 to the earliest of CKD (confirmed, >3 months apart, eGFR<60 mL/min/1.73m 2 ), last visit plus 6 months or 1.2.2015. Poisson regression was used to model associations between CKD and use of two contemporary PI’s (ritonavir boosted atazanavir (ATV/r) and DRV/r), adjusting for demographics, other antiretroviral treatment, renal and HIV-related risk factors. Results: Of 26,939 persons 1,209 developed CKD (incidence rate (IR) 8.6/1000 PYFU [95%CI 8.1-9.1]). 13.1% and 24.8% of the follow-up time (140,966 PYFU) was after starting DRV/r and ATV/r respectively. Median age at baseline was 44 (IQR 38-50) years, median CD4 count was 510 (IQR 370-700) cells/mm 3 , and 28.8%, 35.9% and 35.3%were at low, medium and high 5-year CKD risk estimated by the D:A:D CKD risk score. While the CKD IR was low in individuals unexposed to DRV/r or ATV/r and increased with increasing exposure, after adjustment, only ATV/r (adjusted IR ratio (aIRR) 1.86 [1.58-2.20]), but not DRV/r (1.29 [0.94-1.77]) exposure remained significantly associated with CKD after >4 years (figure). Further multivariate analysis excluding those unexposed to DRV/r showed no statistically significant association between increasing DRV/r exposure and CKD (aIRR 1.21/5 years [0.83-1.75]). After exclusion of those unexposed to ATV/r the CKD rate significantly increased with increasing ATV/r exposure (aIRR 1.24/5 years [1.01-1.52]). The results were similar for individuals at low, medium or high estimated CKD risk (p>0.05, test for interaction). The rate of discontinuing ATV/r, but not DRV/r, was associated with lower eGFR levels (aIRR 1.74 [1.36–2.22] for ATV/r and 1.24 [0.83-1.86] for DRV/r at eGFR<70 vs. >90). Conclusion: In a large heterogeneous cohort of contemporarily treated HIV-positive persons with six years median follow-up, DRV/r discontinuation was eGFR unrelated and more extended DRV/r use was not significantly associated with excess CKD risk, although a similar association as seen with ATV/r could not be ruled out. The previously reported association between gradually increasing risks of CKD with longer use of ATV/r remained. 654 HIV AS A RISK FACTOR OF AIRWAY OBSTRUCTIVE DISEASE Alain Makinson 1 , Sabrina Eymard-Duvernay 2 , Céline Ribet 3 , Lucie Marchand 4 , Maurice Hayot 1 , Gilles Pialoux 5 , Jacques Reynes 6 , Marie Zins 3 , Vincent Le Moing 1 , for the ANRS EP48 HIVCHEST StudyTeam 1 Univ Hosp Montpellier, Montpellier, France, 2 INSERM, Montpellier, France, 3 INSERM, Villejuif, France, 4 France Recherche Nord et Sud Sida-HIV et Hépatites, Paris, France, 5 Tenon Hosp, Paris, France, 6 CHU de Montpellier, Montpellier, France Background: We previously showed high prevalence of chronic obstructive pulmonary disease (COPD) in an all-smoking cohort of HIV-individuals. Whether COPD prevalence is higher in HIV-individuals than in the general population remains to be determined. The objective of this study was to compare the prevalence of airflow obstruction (AO) in HIV- individuals and in age and gender matched individuals from the general population, and to determine whether HIV-status was an independent factor of AO. Methods: HIV-infected individuals were included in the ANRS EP48 HIV-CHEST study (NCT01207986), a multicentre, French, lung cancer screening study with chest CT. Each HIV- individual was randomly matched by age and gender with two individuals from a general population cohort CONSTANCES. All individuals were smokers ≥ 20 pack-years, possibly stopped within the previous 3 years, and aged ≥ 40 years. HIV-individuals also had a CD4 T-lymphocyte nadir count < 350/μL, and a last CD4 T-lymphocyte count > 100/μL. Both populations underwent spirometry without administration of a bronchodilator. The primary endpoint defining AO was the forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio < 0.70 and a FEV1 measure <80 % of the theoretical value. A logistic regression model evaluated the association of AO with age, gender, HIV status, Body Mass Index, smoking (pack-years), and former smoking. Results: 351 HIV-infected individuals were matched to 702 subjects (table); 68 (19%) of HIV-infected versus 60 (9%) of HIV-negative individuals had AO. In multivariate analysis, factors associated with AO were HIV (OR: 2.03, 95% CI (1.33-3.10)), age (per 10 years increase) (OR 1.68, 95% CI (1.23-2.29)), and smoking (per 5 pack-years increase) (OR: 1.10, 95% CI (1.02-1.19)). Adding HCV and history of cannabis inhalation in a sensitivity analysis slightly diminished the association between HIV and AO (OR: 1.71, 95% CI (1.08-2.72)). Conclusion: Prevalence of AO was higher in HIV-smokers aged ≥ 40 years than in age and gender matched smokers from the general population. HIV was an independent risk factor for AO, even after further adjustment for HCV (a proxy for history of intravenous drug use), and cannabis inhalation. Smoking was associated with AO, underscoring the importance of smoking cessation programs. Finally, both high prevalence and increased risk of AO in HIV-individuals that smoke argue for early systematic diagnosis of AO with spirometry in HIV-smokers ≥ 40 years.

Poster and Themed Discussion Abstracts

CROI 2017 280