CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Univ of California Los Angeles, Los Angeles, CA, USA, 2 Los Angeles Biomed Rsr Inst at Harbor–UCLA Med Cntr, Torrance, CA, USA, 3 Univ Texas Houston, Houston, TX, USA, 4 Cedars-Sinai Med Cntr, Los Angeles, CA, USA, 5 Charles R. Drew Univ of Med and Sci, Los Angeles, CA, USA Background: Hepatitis C virus (HCV) infection may increase risk of atherosclerotic disease. Endothelial dysfunction contributes to atherosclerosis, but endothelial function has not been characterized in HIV/HCV co-infection. We hypothesized that endothelial function would be abnormal in HIV/HCV-coinfected persons on suppressive antiretroviral therapy (ART). Methods: We enrolled HIV/HCV-coinfected adults with HIV RNA <50 copies/mL, CD4 + T cell count ≥200 cells/mm 3 , HCV RNA ≥10,000 IU/mL, with no known cardiovascular disease, and measured endothelial function by peripheral arterial tonometry (PAT). Standardized conditions for PAT testing included: fasting and avoidance of vigorous exercise for 12 hours (h), nicotine held for 4h, caffeine/stimulants for 24h, select antihypertensive agents for 24-48h, and vaccines for 14 days. Endothelial dysfunction was defined as reactive hyperemia index (RHI) by PAT ≤1.67 and optimal endothelial function as RHI >2. Wilcoxon rank sum tests were conducted to compare RHI between groups. Multiple linear regression analysis was used to assess predictors of natural log-transformed RHI (lnRHI). Results: Forty-three participants had RHI for analysis; 86%were male, 35% Black, and 40% Hispanic, with median age of 52 years. Median nadir and current CD4 + T cell count were 149 and 502 cells/mm 3 , respectively, median HCV RNA 6.16 log IU/mL, and waist circumference (measured at the level of the iliac crest) 97 cm. Thirty-five % reported current smoking, 9% current stimulant (cocaine or methamphetamine) use, 14% had dyslipidemia, 23% hypertension, 12% cirrhosis, and none had diabetes. Nine (21%) had RHI ≤1.67 and 25 (58%) had RHI <2.0. RHI was similar between those on abacavir (n=15) and those not (median RHI 1.94 vs 1.98, p=0.49), on a boosted HIV-1 protease inhibitor (n=12) vs not (1.98 vs 1.98), and with and without cirrhosis (1.90 vs 1.98, p=0.84). In multiple regression analysis, higher HCV viral load and current smoking were associated with worse lnRHI (see Table). Conclusion: Peripheral endothelial function was suboptimal in the majority of participants in this cohort with untreated HCV and ART-treated, virologically suppressed HIV infection. Whereas degree of HCV viremia does not predict liver disease progression, it may contribute to endothelial dysfunction and cardiovascular morbidity in HIV/HCV- coinfected patients, even with HIV suppression. 590 LEUKOCYTE TELOMERE ATTRITION IS RAPID FOLLOWING HIV BUT NOT HCV SEROCONVERSION Alejandro Gonzalez-Serna 1 , Abhinav Ajaykumar 2 , Izabelle Gadawski 2 , M. Ángeles Muñoz-Fernández 3 , Kanna Hayashi 1 , M.-J. Milloy 1 , P. Richard Harrigan 1 , Helene C. Cote 2 1 BC Cntr for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada, 2 Univ of British Columbia, Vancouver, British Columbia, Canada, 3 General Univ Hosp Gregorio Marañon, Madrid, Spain Background: Age-related diseases are more prevalent in persons living with HIV, suggesting accelerated aging. Both HIV and hepatitis C virus (HCV) infection have been associated with shorter leukocyte telomere length (TL). Whether this TL shortening occurs rapidly following HIV and/or HCV seroconversion or gradually over the chronic infection period is unclear. Methods: In the retrospective study, PBMC TL was measured in 95 subjects enrolled in Vancouver Injection Drug Users Study (VIDUS)/ AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), who subsequently acquired HIV (n=51) or HCV (n=16). PBMCs were collected at two time points: a median of 3 months before and 9 months after seroconversion. Control participants who did not seroconvert (NS) for either virus (n=29) were analyzed at 2 random time points a median one year apart. TL was assayed via monochrome multiplex qPCR. Within-individual TL change between the two time points were compared for each group using the Wilcoxon signed rank test. Results: Compared to pre-seroconversion, TL was significantly shorter (-13%) post-seroconversion in those who acquired HIV [Median 8.2 (6.9-10) vs 9.1 (7.7-11.1), p=0.025], but not among HCV seroconverters [8.4 (7.2-9.9) vs 8.5 (6.9-10), p=0.552] or control non-seroconverters [9.6 (8.8-11.2) vs 9.6 (8.7-11), p=0.353]. Among HCV seroconverters, 31% (5/16) were already HIV+ while 90% (46/51) of the HIV seroconverters were already HCV+. One subject seroconverted for both viruses. Conclusion: The average PBMC TL shortening that occurs with HIV infection is detected within a year of HIV seroconverting. In contrast, the lack of a similarly rapid TL loss with HCV seroconversion suggests that the previously reported association between HCV and shorter TL may be primarily driven by longer term chronic infection. Together, these data suggest that HIV infection modulates cellular aging and immunosenescence very early in infection. 591 MULTIPLE-TEST SCREENING STRATEGIES IMPROVE BIOPSY-PROVEN HSIL-DETECTION IN HIV+WOMEN Dorothy J. Wiley 1 , Elizabeth Chiao 2 , Jeanette Lee 3 , Ashish A. Deshmukh 4 , Scott B. Cantor 5 , Joel Palefsky 6 , Elizabeth A. Stier 7 1 Univ of California Los Angeles, Los Angeles, CA, USA, 2 Baylor Coll of Med, Houston, TX, USA, 3 Univ of Arkansas for Med Scis, Little Rock, AR, USA, 4 Univ of Florida, Gainesville, FL, USA, 5 Univ of Texas MD Anderson Cancer Cntr, Houston, TX, USA, 6 Univ of California San Francisco, San Francisco, CA, USA, 7 Boston Univ, Boston, MA, USA Background: Anal cancer disproportionately affect HIV-infected women. Biopsy-confirmed anal high-grade squamous intraepithelial lesion (aHSIL) is a precancer lesion. There is no consensus for providing aHSIL screening. Thus, we estimated test characteristics for a series of aHSIL-screening strategies. Methods: In a cross-sectional study, anal Dacron-swab specimens for 200 HIV-infected women were tested for abnormal cytology (≥ ASC-US) & high-risk HPVs (hrHPVs) using both hrHPV-E6/E7-mRNA (E6/E7-mRNA) (GenProbe Corp, Marlborough, MA) & hrHPV-DNA (Qiagen Corp., Valencia, CA) assays. High-Resolution Anoscopy with biopsy evaluated tissue for high-grade squamous intraepithelial lesions (bHSIL), an anal cancer precursor, for all subjects. Sensitivity, specificity, positive and negative predictive value of one or more tests to predict bHSIL (test characteristics) were estimated for seven screening strategies (Table): 1) abnormal Dacron cytology, 2) E6/E7-mRNA+, 3) hrHPV-DNA+; 4) E6/ E7-mRNA+ or hrHPV-DNA+, defined as in parallel testing, 5) abnormal cytology, then E6/E7-mRNA+, defined as in series, 6) abnormal cytology, then hrHPV-DNA+ (in series), & 7) E6/E7-mRNA+ then hrHPV-DNA+ (in series). Logistic regression analyses, adjusted for age, compared screening-positive vs. -negative results & were used to determine the benefit of adding hrHPV testing following a positive anal cytology result. Results: Abnormal cytology (55%) & bHSIL (27%) were common. Performance characteristics are listed in Table 1 & show specificity alone is improved using any of the in series screening strategies (p<0.05). Conditional analyses suggest a positive effect of hrHPV-DNA+ or E6/E7-mRNA+ on bHSIL detection, given abnormal cytology: OR=3.04 (1.26, 7.34), OR=7.39 (2.72, 20.09), respectively. Conclusion: Strategies that refer women with abnormal cytology and either positive E6/E7-mRNA or hrHPV-DNA test results to HRA improved anal cancer screening. Our findings suggest E6/E7-mRNA & hrHPV-DNA testing add value to detection of abnormal cytology in comparison to cytology testing alone. Larger studies are needed. 592 MULTITEST SCREENING STRATEGIES ADD VALUE FOR PREDICTING BIOPSY-PROVEN HSIL FOR MSM Dorothy J. Wiley 1 , Hilary K. Hsu 1 , Matthew G. Moran 1 , Jenny Brook 1 , David Elashoff 1 , Martha Ganser 1 , Stephen Young 2 , David Morris 3 , Otoniel Martínez-Maza 1 , Ronald T. Mitsuyasu 1 1 Univ of California Los Angeles, Los Angeles, CA, USA, 2 Tricore Reference Labs, Albuquerque, NM, USA, 3 Desert AIDS Proj, Palm Springs, CA, USA Background: Biopsy-confirmed anal high-grade squamous intraepithelial lesion (bHSIL) is a precursor lesion for anal cancer (AC). AC disproportionately affects HIV-infected MSM. Multi-test screening strategies to assess the value of adding molecular & cytology assays may improve bHSIL screening. Methods: A single-visit RCT evaluated two specimen collection protocols for 301 MSM: Dacron & nylon-flocked (NF) swabs. High-Resolution Anoscopy (HRA) & biopsy evaluated tissue for bHSIL. Dacron- & Nylon-Flocked (NF) cytology specimens were evaluated for atypia (≥ASC-US) & high-risk HPV-DNA (DNA). Dacron-cytology was also tested for hrHPV-E6/E7-mRNA (E6/E7). Receiver-Operator Curves (ROC), adjusted for swab order, age, & smoking, estimated accuracy (AUC) to predict bHSIL for combinations of abnormal cytology & E6/E7- & DNA-test positivity using logistic regression analysis for HIV-infected & uninfected men. Fold-change in AUC compared performance of screening strategies. Results: Men were White (76%), HIV-infected (60%), 55 (+11) years of age, & 47% showed bHSIL. NF-cytology sampling improved accuracy for predicting bHSIL. When combined, NF-DNA & –cytology testing improved accuracy 5%, vs. NF-cytology (AUC=0.8 vs. 0.75, p=0.01) or NF-DNA testing alone (AUC=0.8 vs. 0.75, p=0.02). Paired Dacron-E6/E7 & NF-cytology testing improved accuracy 11% over cytology alone (AUC=0.83 vs. AUC=0.72; p<0.001). Together, Dacron-E6/E7 & NF-DNA screening improved accuracy 5% over DNA

Poster and Themed Discussion Abstracts

CROI 2017 248