Emerging comorbidities in the setting of long- term virological suppression Antonella Castagna San Raffaele Scientific Institute, Milan

Comorbidities in HIV Infection: a tangible problem HIV-infected patients exhibit a worse cardiovascular risk profile after a first episode of acute coronary syndrome. Final results of long term follow up in the PACS-HIV study. F. Boccara How much do smoking, hypertension and diabetes contribute to acute coronary syndrome in HIV-infected patients relative to uninfected patients? MC Sanchez Development of a definition for Rapid Progression of renal disease in HIV-positive persons Lene Ryom (Nielsen) Prevalence and risk factors of subclinical vertebral fractures in a cohort of HIV positive patients K. Luzi

ARV and comorbidities Bone Mineral Density (BMD) Analysis in Antiretroviral (ART)-Naïve Subjects Taking Lopinavir/ritonavir (LPV/r) Combined with Raltegravir (RAL) or Tenofovir/Emtricitabine (TDF/FTC) for 96 weeks in the PROGRESS Study Roula Qaqish Raltegravir as Replacement for PI- or NNRTI-Based ART in HIV-Infected Women with Lipohypertrophy: The Women, Integrase, and Fat Accumulation Trial Jordan E. Lake

Long-term immunological suppression Comorbidities as a Key Issue Reasons for switching Questions to face Patient management

ARV switches in 12% of the undetectable patients since 2010 Virological Suppression (years)

Pooled ECHO and THRIVE Week 48 analysis: Most frequent treatment-related* grade ≥2 AEs † Incidence, % RPV N=686 EFV N=682 P value TMC278 vs EFV Any AE 1631< ‡ Rash 18< ‡ Dizziness 16< ¶ Abnormal dreams/nightmares ¶ Headache 22# Insomnia 22# Nausea 12# *Occurring in at least 2% of patients in either treatment group and excluding laboratory abnormalities reported as an AE; † Safety analyses performed using all available data, including beyond Week 48; ‡ Fisher’s Exact test, predefined analysis for these AEs; ¶ Fisher’s Exact test, post-hoc analysis; # Not determined because not predefined in this analysis Significantly fewer grade 3 or 4 laboratory abnormalities for RPV (11%) vs EFV (18%) 1 1 Cohen C, et al. XVIIIth IAC 2010; Abstract THLBB206

Reasons for switching ARV

Cardiovascular risk associated with abacavir and tenofovir exposure in HIV-infected patients ANY CARDIOVASCULAR EVENT HEARTH FAILURE CORONARY DISEASE CEREBROVASCULAR DISEASE PERIPHERAL ARTERIAL DISEASE Choi AI. et al, AIDS 2011, 25: * P values were<0.01 compared to use of other ART

No association of Myocardial Infarction with Abacavir use: an FDA meta-analysis Ding X, CROI 2011

Long-term glucose tolerance in highly experienced patients receiving NRTI-sparing regimens A.Bigoloni, abstract TUPE257 IAS 2011 RED (15 pts) = RAL, ETR, DRV/r REM ( 24 pts)= RAL, ETR, DRV/r Diabetes diagnoses by OGTT in 5/39 patients

Percent changes in Lumbar Spine and Hip BMD for 4 Treatment Arms (substudy of ACTG A5202) McComsey GA. et al, JID 2011: 203:

96 weeks Bone Mineral Density (BMD) Analysis /Emtricitabine (TDF/FTC in the PROGRESS STUDY

CG, male, 48 years, HIV infection since 1988, DRV/r+TDF/FTC An ARV switch may be an opportunity for the patient There is a need to sign a new patient contract

Switches: questions to face Risks involved in continuing existing regimen Risk of encountering new toxicity Risk of virological failure Risk of resistance Risk of viral escape in reservoirs Rescue regimens in the case of failure Patient management costs

Management of switch Evaluate the weight of the potential comorbidity in the context of the patient’s global prognosis and the possible risk of developing other comorbidities Discuss the risks/benefits of continuing the ongoing regimen or introducing a new regimen Consider the active/proactive switch as part of the global treatment of the patient in terms of interventions and timing Explain the expected outcome, and measure the observed effect in the right manner and at the right time