ART and toxicities: CNS

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ART and toxicities: CNS

Aims of studies Incidence and survival of CNS opportunistic diseases 1996 – 2007 - HIV encephalopathy, PML, toxoplasmosis and cryptococcal meningitis CPE score of cART prescribed between 1996 - 2007 - association between CPE score and demographics or clinical parameters - assess if higher CPE scores associated with reduced incidence of CNS opportunistic diseases and longer survival UK Collaborative HIV Cohort (CHIC) Study Observational cohort initiated in 2001 Dataset currently includes 32,607 patients from 10 UK centres

Incidence of CNS diseases 1996 - 2007 Number of subjects Incidence rate per 1000 PY 13.1 4.3 3.4 3.3 2.3 1.0

Survival of CNS diseases PML HIVe TOXO CRYP 5 year survival estimates PML HIVe TOXO CRYP 46.5% 59.8% 70.4% 71.4%

Median CPE score (2010) of cART Median (IQR) CPE score 1996/97 1998/99 2000/01 2002/03 2004/05 2006/08

CPE (2010) score % subjects CPE score CPE score of cART Majority of subjects (80%) started cART with a CPE score of 5-9 % subjects But 1998 (approx 10%) did not CPE score

Results – multivariable analysis Low (4 or less) CPE scores significantly associated* with - Non-white ethnicity Prior ARV-experience Starting cART 1996-99 or 2004-07 Lower pre-treatment plasma CD4+ cell count Older subjects *p< 0.005 all cases Significant* differences in gender, HIV-risk group and ethnicity existed between CPE strata

Results – incidence of CNS diseases CPE score not significantly associated with incidence of CNS diseases

Results – overall survival Initial CPE score Most recent CPE score Adjusted CPE Score RR (95% CI) p-value <4 1 0.03 0.0001 5-7 0.80 (0.66, 0.97) 0.81 (0.66, 0.98) 8-9 0.78 (0.64, 0.95) 0.80 (0.64, 0.98) >10 0.71 (0.56, 0.89) 0.83 (0.66, 1.04) Off treatment 1.73 (1.40, 2.14)

Summary Changes to CPE score of cART regimens over study period in UK CHIC No association between CPE score and development of CNS disease Significant associations observed between latest CPE score and mortality Choice of cART regimen (and therefore CPE score) varies significantly according to clinical status of patient – this should be considered when utilising the CPE score as research tool Observed changes to CPE score of cART prescribed over study period within UK CHIC Significant associations observed between latest CPE score and mortality – likely to reflect individualised prescribing for those deteriorating clinically, or toxicity and complications from complex cART regimens