CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: We assessed the association of CD4/CD8 ratio and serious NCDs (cardiovascular [coronary artery, cerebrovascular, and peripheral vascular disease], malignancy, liver, and renal diseases) in a cohort of HIV-infected adults after their first year of suppressed HIV RNA (defined as baseline). We examined patient characteristics by baseline CD4/CD8 ratio and CD4/CD8 ratio change from baseline by linear regression. We used Cox proportional hazard models to assess baseline CD4/CD8 ratio and risk of future NCDs. Results: Between 1998-2010, 1700 patients achieved virologic suppression for one year and were included in this study (median follow-up time=3 years). Compared to those with CD4/CD8 ratio >0.7, patients with low CD4/CD8 ratio (<0.4) were older (median 44 vs. 40 years, p <0.01), more likely to be male (86 vs. 70%, p <0.01), and had lower CD4+ lymphocyte counts (median 279 vs. 640 cells/mL, p <0.01). There was no difference in prior ART or follow-up duration. Among those with consistent virologic suppression after three years (n=454), older patients (>50 years) had lower CD4/CD8 gain compared to younger patients (<40 years), after adjusting for baseline ratio (beta = -0.07, p =0.03). There were 123 serious NCDs, including 48 cardiovascular disease (CVD) and 30 cancer events (median time to first CVD or cancer event=2.3 years). Compared to patients with no NCDs during follow-up, only those with CVD and cancer outcomes had statistically lower baseline CD4/CD8 ratios (see Figure). In a model adjusting for age, sex, and CD4+ lymphocyte count, a higher CD4/CD8 ratio remained associated with a lower risk of CVD and cancer events (composite aHR per 0.1 increase = 0.90 [95% CI: 0.81-1.00]). An interaction term for age and CD4/CD8 ratio was not statistically significant ( p =0.46).

Distribution of CD4/CD8 ratio by non-communicable disease (NCD) outcomes in a cohort of 1,700 virologically suppressed HIV-infected adults, 1998-2010 Conclusions: Low CD4/CD8 ratio after one year of suppressed HIV RNA was independently predictive of serious CVD and cancer events. Older adults had lower CD4/CD8 ratio and had less improvement in CD4/CD8 ratio over time. Further study of CD4/CD8 ratio as a biomarker for immunosenescence and risk factor for CVD and cancer in aging HIV-infected adults is needed. 742 Relationship Between Confirmed eGFR and Cardiovascular Disease in HIV-Positive Persons Lene Ryom 1 ; Jens D. Lundgren 1 ; Peter Reiss 2 ; Michael Ross 3 ; Christoph Fux 4 ; Philippe Morlat 7 ; Olivier Moranne 5 ; Colette Smith 6 ; Caroline Sabin 6 ; Amanda Mocroft 6 On Behalf of the D:A:D Study Group 1 CHIP, Department of Infectious Diseases and Rheumatology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark; 2 Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; 3 Division of Nephrology, Mount Sinai School of Medicine, New York, New York City, NY, US; 4 Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland; 5 Nephrology department, Public Health department, CHU Nice, Nice, France; 6 University College London, London, United Kingdom; 7 University of Bordeaux, INSERM U 897, CHU de Bordeaux, Bordeaux, France Background: While the association between impaired kidney function and cardiovascular disease (CVD) is well established in the general population, this association remains poorly elucidated in HIV-positive individuals. As prior studies in HIV have focused on unconfirmed measures of kidney function, which are subject to random variation and acute illness, the influence of sustained kidney impairment is less clear. Methods: D:A:D study participants with >2 eGFRs (Cockcroft Gault) measured after 1/1/2004 were followed until the earliest of CVD, last visit plus 6 months or 1/2/2013. CVD was defined as centrally validated (fatal and non-fatal) myocardial infarction, stroke, angioplasty, bypass, or carotid endarterectomy. Poisson regression stratified according to confirmed current eGFR level was used to model the incidence rate ratios of CVD, while adjusting for demographics, antiretroviral treatment, traditional HIV, cardiovascular and renal risk factors. Results: During a median follow-up of 6.3 years (IQR 4.1-7.9) 1,033 of 34,793 included persons developed CVD (incidence 5.1/1000 PYFU [95% CI 4.8-5.4]). Those included were predominantly Caucasian (48%), male (74%), had homosexual HIV transmission (46%), a median age of 41 years (IQR 35-48), CD4 count of 440 cells/mm 3 (IQR 290-623) and a median time between eGFRs of 3.8 months (IQR 2.8-5.7). There was a clear relationship between confirmed eGFR at baseline and incident CVD with 1.7% [95% CI 1.5-1.9] estimated to have progressed to CVD at 5 years among those with eGFR >90 ml/min/1.73m 2 , increasing to 23.4% [95% CI 6.9-39.8%] among those with eGFR <30 ml/min/1.73m 2 . The strong relationship between a low confirmed current eGFR and CVD in unadjusted analyses was primarily explained by increasing age in adjusted analyses, although a strong trend for increased CVD rates with decreasing eGFR levels remained, largely driven by high rates in those with eGFR <30 ml/min/1.73m 2 (figure). This finding was consistent in different age groups (p=0.43, test for interaction). Analyses were consistent after accounting for death as a competing risk for CVD.

Poster Abstracts

456

CROI 2015