1. Increased clinical events in HIV-infected patients who achieve full virologic suppression but fail to attain a CD4 count ≥ 200 cells/mm 3 after one year of combination antiretroviral therapy (cART). M.R. Loutfy 1,2, B. Yip 3, D. Moore 3, J. Raboud 2, S. Shen 2, J.S.G. Montaner 3, R. Hogg 3 1 Maple Leaf Medical Clinic, Toronto, Ontario; 2 University of Toronto, Toronto, Ontario; 3 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada Background Some patients starting combination antiretroviral therapy (cART) achieve full viral suppression ( 200c/mm 3 – a syndrome known as immunologic discordance. The purpose of our study was to determine if such patients, with immunologic discordance, are at greater risk of clinical events (development of an AIDS-defining illness or death). Objective Methods The population-based cohort consists of HIV-infected individuals, 18 years or older, in British Columbia, Canada, who initiated triple cART between 08/1996 and 09/2003. To be included in the analysis, patients must have had a baseline CD4 50 copies/mL and have achieved a viral load of <50copies/mL on two sequential occasions within the first year of cART. The primary endpoint was non-accidental death or development of an AIDS-defining illness. Subjects were followed until death, development of AIDS, VL >50c/mL or 09/2004. The predictor of interest was the one-year CD4 count categorized as <200c/mm 3 or ≥200c/mm 3. Univariate Cox-proportional hazard regression was used to model the primary predictor and other covariates on the occurrence of a clinical event. Univariate Cox Regression: All Clinical events Conclusion HIV-infected patients taking cART who achieve complete viral suppression but fail to have a CD4 cell increase above the desired target of ≥200c/mm 3 have an increased rate of clinical events within the first year of starting cART. If the CD4 count did not rise ≥200c/mm 3 after one year, there appears to be a trend to increased risk of clinical events thereafter. This is potentially an important concern for patients who achieve viral suppression with inadequate CD4 count response and needs to be evaluated with a larger sample size and more follow-up. Correspondence: mloutfy@nygh.on.ca Acknowledgements: We thank Bonnie Devlin, Elizabeth Ferris, Nada Gataric, Kelly Hsu, Myrna Reginaldo, and Peter Vann for their research and administrative assistance. Baseline Characteristics (n=299) Immunological and Clinical Responses Both p > 0.05 CD4 < 200 CD4 ≥200 n (after 1 year of cART)97 patients (32.4%)202 patients (67.6%) Clinical events overall*10/97 (10.3%)17/202 (8.4%) Clinical events (after 1 year of cART)4/97 (4.1%)5/202 (2.5%) *Clinical event occurred at a median time of 2.2 months after initiation of cART. Univariate Cox Regression: Clinical events after Year 1 Results 21 subjects (7.02%) experienced an AIDS-defining event, of which 3 subjects experienced 2 events simultaneously. The AIDS-defining events that occurred in the study were cytomegalovirus disease (1), AIDS dementia/HIV encephalopathy (3), Herpes simplex infection, chronic mucocutaneous (1), Kaposi’s Sarcoma (5), Lymphoma, primary in the brain (1), Mycobacterium avium complex or M. Kansasii (4), Mycobacterium tuberculosis (2), Lymphoma, non-Hodgkins (2), Pneumocystis carinii pneumonia (3) and Progressive multifocal leukoencephalopathy (2). There were 6 events of death (2.01%) HR95% CIp-value Adherence >95%0.340.15-0.770.009 Baseline CD40.46 per 100 cells0.23-0.920.027 Time-dependent CD40.48 per 100 cells0.30-0.770.002 Failure to attain CD4 ≥2003.080.98-9.710.055 HR95% CIp-value Adherence >95%0.170.04-0.620.008 Baseline CD41.05 per 100 cells0.36-3.070.934 Time-dependent CD40.42 per 100 cells0.21-0.860.017 Failure to attain CD4 ≥2003.940.85-18.20.080 Overall (n=299) CD4 < 200 (n=97) CD4 ≥200 (n=202) p-value Age in years (median, IQR)42 (35, 49)43 (37, 49)41 (35, 49)0.430 Male257 (86.0%)86 (88.7%)171 (84.7%)0.351 Injection Drugs46 (15.4%)19 (19.6%)27 (13.4%)0.163 HIV-AIDS81 (27.1%)34 (35.1%)47 (23.3%)0.32 Number of ARVs (median, IQR)3 (3, 3) 1.00 NNRTI in first regimen147 (49.2%)39 (40.2%)108 (53.3%)0.032 Viral Load (c/mL) (median, IQR) >100,000 (71, >100K) >100,000 (69, >100K) >100,000 (75, >100K) 0.664 CD4 (cells/mm 3 ) (median, IQR)80 (30, 140)40 (10, 80)120 (50, 160)<0.001 logo