Risk of tuberculosis following HIV seroconversion in low- burden tuberculosis countries Sara Lodi, Antonella d’Arminio Monforte, Julia del Amo, Sophie Abgrall, Caroline Sabin, Charles Morrison, Hansjakob Furrer, Roberto Muga, Kholoud Porter, Enrico Girardi on behalf of the CASCADE collaboration in EuroCoord

Objectives and methods Knowledge of clinical epidemiology of TB risk at all stages of HIV infection is needed to inform on time for TB preventive interventions in low-burden TB countries We used CASCADE data from patients with well known date of HIV seroconversion in low-burden TB countries to:  Estimate TB incidence rates following HIV seroconversion in the pre-cART era  Establish if TB risk after cART differs from post- seroconversion risk  Explore role of immunosuppression on the risk of TB following cART initiation

Risk of TB in pre-cART era Incidence rate/1000 PY Years following seroconversion N TB PY individuals at risk of TB 243 TB diagnoses at a median CD4 cell count of 125 cells/mm 3 50% MSM, 26% IDU

Risk of TB after cART initiation Incidence rate/1000 PY Years following cART initiation N PY TB rate in general population: /1000 PY (WHO 2009) individuals at risk of TB 120 TB diagnoses at a median CD4 cell count of 195 cells/mm 3

Predictors of TB after cART IRRP Risk group0.001 Sex between men1 Sex between men and women Injecting drug users Other/unknown Country of origin0.054 Low-burden TB country1 Mid-burden TB country Sub-saharan Africa Unknown Age at cART initiation (10-year increase) Current CD4 count<0.001 >= < Duration of cART> 1 year HIV RNA at cART (1 log increase) % CI IRRP Risk group Country of origin Mid-burden TB country Sub-Saharan Africa Age at cART initiation (10-year increase) Current CD4 count <0.001 ≥ < Duration of cART> 1 year HIV RNA at cART (1 log increase) % CIIRRP Risk group Sex between men1 Sex between men and women Injecting drug users Other/unknown Country of origin Low -burden TB country Unknown Age at cART initiation (10-year increase) Current CD4 count < Duration of cART> 1 year HIV RNA at cART (1 log increase) % CI

Implications  Risk of TB increases with time since HIV seroconversion. Prevention should be implemented in early HIV infection.  Both post-seroconversion and post-cART TB rates are higher than those recorded in general population (WHO 2009). HIV infected patients are still at high risk of TB.  Current CD4 cell level is the dominant predictor of TB risk after cART initiation. TB prevention would be improved by antiretroviral treatment policies that minimise the time patients spend with low CD4 count.