Switching strategies and ARV treatment costs

February 2014 Switching strategies and ARV treatment costs Josep M Llibre/Bonaventura Clotet Fundació Lluita contra la SIDA Hosp Univ Germans Trias i Pujol Badalona

Rationale. Spain is under a huge economic crisis that also (and particularly) involves the Public Health System. The Government spending on prescription drugs has been drastically reduced. The value of prescriptions in the hospital sector increased 55% from 2008 to 2011, and hospital-based expensive prescriptions have been identified as a special target for cost-cutting measures: Chemotherapy agents. Antiretrovirals (in Spain ARVs are supplied through Hospital pharmacies). Biologic agents. Others: PegIFN, anti-hep C antivirals, EPO, etc. HIV Units are forced to immediately reduce their antiretroviral budgets. Llibre JM. 10 TH Eur Meeting on HIV & Hepatitis. Barcelona (Spain), 28-30 March, 2012. Invited lecture. Llibre JM et al. ClinicoEcon Out Res 2013; 5:215-221.

Rationale. The case of an HIV Unit. In a 600 bed University-affiliated Hospital in Barcelona (Spain) a reference HIV Unit gives antiretroviral treatment to 2401 HIV-1-infected subjects. Antiretrovirals accounted for 47.8% of the overall hospital pharmacy budget (excluding Oncology): 17,898.758 (out of 37,463.682, including treatments of hospitalized subjects) in 2011. Three main areas are identified in order to reduce the ARV budget: Inclusion of subjects into Clinical Trials (treatment payed by the trial). Reduction in the prize of ARV by pharma drugmakers. Cost-cutting measures undertaken in patients receiving ART. Llibre JM. 10 TH Eur Meeting on HIV & Hepatitis. Barcelona (Spain), 28-30 March, 2012. Invited lecture. Llibre JM et al. ClinicoEcon Out Res 2013; 5:215-221.

Results. Treatment changes undertaken. 673 total treatment changes undertaken during the period (187% increase vs the same period May-Nov in 2010). 28% of all the patients treated receive a treatment change. 378 (16% of overall cohort) subjects treated receive a cost-cutting measure. Treatment change goal Month Cost ( ) N Percentage Cost-cutting measures -87.409,80 378,00 56,17% Inclusion in Clinical Trials -2.712,00 27,00 4,01% Ends a Clinical Trial 3.826,80 9,00 1,34% Toxicity 12.022,50 76,00 11,29% Toxicity plus adherence or PK issues 1.406,70 2,00 0,30% Virological failure 17.657,85 44,00 6,54% Others 8.100,00 31,00 4,61% Naives, news in the center or ART reinitiation 52.995,60 64,00 9,51% PEP 16.710,00 22,00 3,27% Total general 30.962,85 673,00 100,00% Llibre JM. 10 TH Eur Meeting on HIV & Hepatitis. Barcelona (Spain), 28-30 March, 2012. Invited lecture. Llibre JM et al. ClinicoEcon Out Res 2013; 5:215-221.

Llibre JM. 10 TH Eur Meeting on HIV & Hepatitis. Barcelona (Spain), 28-30 March, 2012. Invited lecture. Llibre JM et al. ClinicoEcon Out Res 2013; 5:215-221. Results. Treatment changes undertaken. CCM: 412 treatment changes undertaken in 378 subjects switching their regimen to a less expensive treatment. ART Change N % of changes Truvada Kivexa 129 31.31 DRV/r monotherapy 63 15.29 LPV/r monotherapy 39 9.47 NVP, switch to 33 8.01 RAL substitution 29 7.04 RAL withdrawal 23 5.58 DRV/r dose reduction 20 4.85 3TCgen changes 15 3.64 ATV/r 300/100 ATV 400 14 3.40 ETR withdrawal or substitution 11 2.67 Atripla, switches to 10 2.43 MVC dose reduction or withdrawal 8 1.94 Inactive NRTI withdrawal 5 1.21 TPV withdrawal 3 0.73 Others 10 2.43 TOTAL 412 100%

Llibre JM. 10 TH Eur Meeting on HIV & Hepatitis. Barcelona (Spain), 28-30 March, 2012. Invited lecture. Llibre JM et al. ClinicoEcon Out Res 2013; 5:215-221. Results. CCM effect in the overall framework. Total savings ( ) achieved per month with every cost saving category.? * Median ARV pharma Industry discount during the period: 14.5%.

Results. 48-week outcomes CCM CCM N = 378 Remaining on the same ARV regimen (CCM) 318 (84.1%) Reasons for changing the regimen: Adverse events related with the new regimen not related with the new regimen Virological failure * PK interactions Treatment withdrawal 26 (6.9%) 17 (4.5%) 8 (2.1%) 7 (1.9%) 2 (0.5%) * Defined as two consecutive plasma HIV-1 RNA >50 c/ml. 1 tuberculosis (rifampin), 3 hepatitis C virus antivirals, 3 corticosteroids (PI/rs). 14 patients received a new CCM to further reduce the cost of their ART; 4 subjects reduced the number of pills of their ART. Llibre JM. CROI 2014, March 3 to 6, 2014. Boston, MA, US. #439. *Week 24 window defined as 6weeks prior or after scheduled Week 24 study visit

Llibre JM. 10 TH CROI 2014, March 3 to 6, 2014. Boston, MA, US. #439. Results. 48-week outcomes CCM No grade 3-4 drug-related toxicities. All them with plasma HIV-1 RNA < 50 c/ml at 48 weeks. Drug Toxicity (any grade, related with the CCM) Grade n(%) of CCM n(%) overall Overall Abacavir Lopinavir/r Nevirapine Darunavir/r Efavirenz Etravirine - GI (diarrhea, abdominal discomfort) asthenia, myalgias Diarrhea Rash Diarrhea CNS Neuropsychiatric Rash 1 1-2 1-2 1 1 2 8/129 (6.2%) 5/39 (12.8%) 4/33 (12%) 2/10 (20%) 26/378 (6.9%) 8 (2.1%) 5 (1.3%) 4 (1.0%) 2 (0.5%) 2 (0.5%) 1 (0.3%) One increase in hep B DNA, 2 Grade 1 AST/ALT, 1 Grade 2 AST/ALT (1 LPV/r mono, 3 TDF/FTC to ABC/3TC) Virological failures: 8/378 (2.1%). 4 PI/r mono, 3 triple PI/r, 1 triple unboosted ATV. Prior GRT GRT at failure HIV-1 RNA at 48 weeks Wild-type: 5 Wild-type: 2, Not evaluable: 1, not done: 2 4: < 50 c/ml; 1: 340 c/ml Not done: 3 Not evaluable: 1, Not done: 1 Resistance in RT and PRO *: 1 * RT: M184V L210W T215Y. PR : L10I, K20R, V32I, M36I, M46I, I54V, Q58E, A71L, V82A, I84V, L90M. Treated with ATV/r + ABC/3TC. *Week 24 window defined as 6weeks prior or after scheduled Week 24 study visit 2: <50 c/ml; 1: 281 c/ml

Results. 48-week outcomes CCM Direct initial drug costs saving: 87.140 /month (1,045.680 /48 w) FINAL TOTAL COSTS, 48 w GlobalTreatment Changes during 48wks, cost /year 40.124 Extra visits 2.553 Supplemental tests 2.971 TOTAL 45.648 FINAL REAL NET SAVINGS 1,000.032 Llibre JM. 10 TH CROI 2014, March 3 to 6, 2014. Boston, MA, US. #439.

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