title: Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.
abstract: The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation.
authors.affiliation: Philosophy of Law Department, Law School, Alcala University, Alcalá de Henares, Madrid, Spain; Human Rights Institute 'Bartolomé de las Casas', Legal Clinic on HIV/AIDS, Carlos III University, Getafe, Madrid, Spain. Electronic address: miguelangel.ramiro@uah.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ramiro
authors.affiliation: Lluita contra la SIDA Foundation, Badalona, Barcelona, Spain; HIV Unit, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000191:economics* / Q000600:supply & distribution / Q000627:therapeutic use; D017046:Cost Savings / Q000941:ethics / Q000331:legislation & jurisprudence; D004334:Drug Administration Schedule; D004338:Drug Combinations; D057915:Drug Substitution / Q000191:economics / Q000941:ethics; D016568:Drugs, Generic / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D057172:Economic Recession; D005060:Europe; D015658:HIV Infections / Q000188:drug therapy; D054625:Healthcare Disparities; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000191:economics* / Q000600:supply & distribution; D055118:Medication Adherence; D009313:National Health Programs / Q000191:economics*; D010349:Patient Compliance; D028701:Patient Rights; D011634:Public Health; D013030:Spain; D013810:Therapeutic Equivalency
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D016568:Drugs, Generic; D019259:Lamivudine
keywords: Derecho a la protección de la salud; Drug substitution; Drugs, generic; Equality and non discrimination; Fixed-dose combination antiretroviral therapy; Highly active antiretroviral therapy; Igualdad y no discriminación; Medicamento genérico; Right to healthcare protection; Sustitución de medicamento; Terapia antirretroviral combinada a dosis fija; Terapia antirretroviral de gran actividad