Costo-efficacia del monitoraggio immunologico standard. Enrico Girardi UOC Epidemiologia Clinica INMI L. Spallanzani, Roma

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1 Costo-efficacia del monitoraggio immunologico standard Enrico Girardi UOC Epidemiologia Clinica INMI L. Spallanzani, Roma

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3 Beneficio clinico del monitoraggio della conta CD4 Studi in Paesi ricchi There was a benefit to testing for CD4 cell count in the first 48 weeks of treatment, to identify patients who have.. a higher risk of progression to AIDS after 48 weeks, for the 'responder' patients in the ARTEMIS trial who had both HIV-1 RNA below 50 copies/ml and rises in CD4 cell count equal or above 200 cells/μl, there appears to be little clinical benefit. Girard PM et al : Can we stop CD4+ testing in patients with HIV-1 RNA suppression on antiretroviral treatment? AIDS those with HIV-1 RNA <200 copies/ml and CD4 counts 300 cells/µl, had a 97.1% probability of maintaining durable CD4 200 cells/µl for 4 years. When non-hiv causes of CD4 lymphopenia were excluded, the probability rose to 99.2%. Gale HB, et al. :Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/μl and HIV-1 suppression? Clin Infect Dis Among 1004 patients with HIV infection on ART, none [95% confidence interval (CI) 0 2.3%] of the 162 clinical decisions to change or stop treatment were influenced by CD4 cell counts. Chow EFP, et al.: Routine CD4 cell count monitoring seldom contributes to clinical decision-making on antiretroviral therapy in virologically suppressed HIV-infected patients. HIV Med 2015

4 Can We Break the Habit of Routine CD4 Monitoring in HIV Care? Paul E. Sax, Clinical Infectious Diseases 2013 Provider: Your blood tests look great viral load undetectable, CD4 cell count550, liver and kidney tests all fine. Patient [worried]: CD4 550? It was 860last time that s a drop of over 300 cells! Provider [trying to be reassuring]:there s a lot of variability in the CD4 count, especially when it s normal like yours. Plus, the most important test for showing whether your treatment is working is the viral load. Patient [unconvinced]: Okay. [A brief pause]: Hey, maybe it s because I had a cold that day. Or because I did it too early in the morning and without breakfast! And it s always been lower when I do it on a Monday. Should we repeat the test?

5 Beneficio clinico del monitoraggio della conta CD4 Studi in Paesi a risorse limitate the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P=0.002) or the CD4 arm (1.49, P=0.032). Mermin J et al.: Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receivingantiretroviral therapy in Uganda: randomised trialbmj 2011 CLIN was not non-inferior to LAB [HIV viral load and CD4 every 6 mo]; the mean increase in CD4 cell count was 175 cells per μl (SD 190,95% CI ) with CLIN and 206 (190, ) with LAB (difference 31 [ 63 to 2] and non-inferiority margin 52 [ 58 to 45]). Laurent C et al.: Monitoring of HIV viral loads, CD4 cell counts, and clinical assessments versus clinical monitoring alone for antiretroviral therapy in rural district hospitals in Cameroon (Stratall ANRS12110/ESTHER): a randomised non-inferiority trial. Lancet Infect Dis 2011

6 Costo- efficacia del monitoraggio della conta CD4 Studi in paesi a risorse limitate clinical/cd4 monitoring compared withclinical monitoring alone increases costs by $ ( , ) and averts DALYs (ICER=$174 per DALY). compared with clinical monitoring alone, monitoring of routine CD4 cell count is considerably more cost effective.. Kahn JG et al.: CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study.; BMJ 2013 LAB increased costs by a mean of $489 (SD 430) per patient and saved life-years compared with CLIN (ICER of $4768 [95% CI ] per LYS) Laboratory monitoring was not cost effective.. according to the $367 costeffectiveness threshold (three times per-person GDP in Cameroon). Boyer S et al.: Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER): a cost-effectiveness analysis. Lancet Infect dos 2013

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8 Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen We use modelling to synthesize evidence and evaluate the costeffectiveness... We find that viralload-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring,

9 Potential Savings by Reduced CD4 Monitoring in Stable Patients With HIV Receiving Antiretroviral Therapy Emily P. Hyle, MD 1 ; Paul E. Sax, MD 2 ; Rochelle P. Walensky, MD, MPH JAMA Intern Med. 2013;173(18): We project that the current strategy of biannual CD4 monitoring costs $20.5 million/year at the conservative cost of $38/test; reducing CD4 monitoring to once/year could result in annual savings of $10.2 million Many clinicians routinely use the more expensive CD4% (frequently including quantitative CD8 count, $67/test), in which case annual savings could reach $18.1 million.

10 Potenziali risparmi in Italia da un monitoraggio immunologico meno frequente Tariffa una determinazione sottopopolazioni linfocitarie 17,09 (X3?) ( GU ) Potenziale risparmio annuo in Italia dall eseguire 1 conta in meno per anno per paziente Costo mese dei regimi raccomandati di terapia antiretrovirale : (Linee Guida Italiane sull utilizzo dei farmaci antiretrovirali Dicembre 2015)

11 Monitoraggio immunologico in HIV Raccomandazioni delle Linee Guida EACS 2015 SIMIT Ministero Salute 2015 DHHS USA 2016

12 Immunological Monitoring in Patients with HIV - DHHS 2016 Despite strong evidence linking low CD4 cell counts and increased morbidity during ART-mediated viral suppression, no adjunctive therapies that increase CD4 cell count beyond levels achievable with ART alone have been proven to decrease morbidity or mortality. The CD4 count response to ART varies widely, but a poor CD4 response in a patient with viral suppression is rarely an indication for modifying an ARV regimen. In patients with consistently suppressed viral loads who have already experienced ART-related immune reconstitution, the CD4 count provides limited information. Frequent testing is unnecessary because the results rarely lead to a change in clinical management Adding ARV drugs to an already suppressive ART regimen does not improve CD4 cell recovery, and does not reduce morbidity or mortality.

13 Conclusione e Statement Proposto La conta dei linfociti CD4 fornisce informazioni importanti nella valutazione iniziale dei pazienti con HIV o in caso di eventi clinici e fallimento virologico della terapia In pazienti trattati con soppressione virale stabile l informazione fornita da questo test è limitata. Il test dovrebbe essere eseguito una volta l anno o meno. Questa prassi può determinare significativi risparmi che potrebbero essere reinvestiti per garantire l accesso alla terapia ad un numero maggiore di pazienti senza risorse aggiuntive.