1. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Abstract: WEABO205. HIV infection was associated with an increased risk of hip fracture, independently of age, gender and co-morbidities: a population-based cohort study. Authors : H. Knobel 1, R. Güerri 1, D. Prieto 2, J. Villar 1, A. Díez 3, E. Lerma 1, M. Montero 1, A. González 1, A. Guelar 1 Institutions: 1 Hospital del Mar., Infectious Diseases., Barcelona, Spain, 2 Universitat Autònoma de Barcelona, IDIAP Jordi Gol Primary Care Research Institute, Barcelona, Spain, 3 Hospital del Mar, Internal Medicine, Barcelona, Spain

2. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Author conflict of interest Consultation fees to: -Gilead Sciences -ViiV healthcare -Abbvie -Bristol Myers Squibb -Janssen-Cilag

3. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Background HIV – infected patient live longer, and being confronted with health challenges related to aging. Morbidities that were not classically considered to be HIV related are now found associated with ongoing HIV replication, chronic immune activation, and with long-term HAART. Numerous studies have found that HIV-infected patients have lower bone mineral density (BMD) compared with the general population, but studies analyzing whether low bone density actually leads to greater incidence of fractures in HIV-infected patients have been inconclusive.

4. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods I  Study design. A population-based cohort study was conducted to explore the association between HIV infection and hip and other major osteoporotic fracture risk.  Participants. The Spanish public health-care system covers the practical totality of the population. General practitioners (GPs) play an essential role. Data was obtained from the SIDIAP Q Database, which contains clinical information for >2 million patients in Catalonia, Spain (30% of the total population). All patients aged ≥40 years in the database in the period 2007 to 2009 were eligible for this study (N = 1,118,587). Participants with a clinical diagnosis of HIV infection were identified

5. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods II  Ascertainment of fractures We screened the database to ascertained incident hip and osteoporotic major fractures (clinical spine, wrist/forearm, pelvis and proximal humerus) in the population aged 40 years or older. We obtained data on incident fractures involving hospital admission from the Hospital Discharge Episodes database.  Statistical analyses Cox regression models were used to estimate Hazard Ratios (HRs) and 95% CI for the HIV-infected VS uninfected participants. Models were adjusted for age, gender, body mass index (BMI), smoking status, alcohol consumption, oral glucocorticoid use, and co-morbid conditions (as the Charlson Index).

6. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results Among 1,118,156 eligible participants, we identified 2,489 (0.22%) HIV-infected, with a median follow-up of 3 years. During the study 41,907 (3.75%) patients died, 178 (7.2%) of HIV-infected and 41,729 (3.7%) of the uninfected patients. During the study 49 and 24,408 of clinical fractures (12 and 7,299 hip fractures) were observed in the HIV-infected and in the uninfected patients respectively. The unadjusted fracture incidence rates were 8.03/1,000 patient-years (95%CI 6.07-10.62) in the HIV-infected and 7.93/1,000 (7.83-8.03) in the non-infected patients. The HR for hip fracture in HIV/AIDS was 4.7 (2.4-9.5; p< 0.001) and for all clinical fractures was1.8 (1.2-2.5; p=0.002) in the adjusted model including all potential confounders.

7. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Age-specific fracture incidence-rates (/1000 person-years) in HIV infected VS uninfected patients.

8. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Hazard Ratio (HR) for hip, and all clinical fractures for HIV infected VS uninfected patients. Number of fractures Fracture IR/1,000 py [95%CI] Age & Gender- adjusted HR [95%CI]; p-val Multivariate adjusted HR* [95%CI]; p-val HIP FRACTURES HIV Uninfected7,299 2.37 [2.31-2.42]REF HIV Infected122.03 [1.15-3.57] 6.16 [3.49-10.86]; p<0.001 4.72 [2.35-9.47]; p<0.001 ALL CLINICAL FRACTURES HIV Uninfected24,4087.93 [7.83-8.03]REF HIV Infected498.03 [6.07-10.62] 2.67 [2.01-3.53]; p<0.001 1.75 [1.24-2.48]; p=0.002 IR = incidence rate; py = person-years at risk; CI = confidence interval. a Further adjusted for body mass index, smoking, alcohol use, oral corticosteroid use, and the following comorbid conditions (as listed in the Charlson comorbidity index): type 2 diabetes, chronic obstructive pulmonary disease, heart failure, myocardial infarction, rheumatoid arthritis, cardiovascular disease, peripheral vascular disease, renal failure, liver disease, malignancy, paraplegia, ulcer, and dementia.

9. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Conclusion We found a strong association between HIV infection and hip fracture incidence, with an almost 5-fold increased risk in the HIV- infected patients, independently of gender, age, body mass index, smoking, alcohol consumption and other co-morbidities. We report a 75% higher risk of all clinical fractures among HIV-infected patients.

10. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Discussion Limitations. -The lack of individual validation of each one of the fractures observed. - The lack of detailed information on HIV infection as well as on antiretroviral therapies used. - The low number of HIV-infected patients included among the elderly suggests that the age-stratified results should be interpreted with caution. Strengths -The high representativeness of the data used (covers 30% of the total population) - Loss to follow-up is low (<2.5%) when compared with other cohort studies, which limits the possibility of loss to follow-up bias.

11. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Thank You Hospital del Mar. Barcelona. Spain