Evidence based practice to research clinical information on adverse effects associated to antiretroviral therapy

C Abrantes1, AC Rama1,3, MM Caramona1,2, A Meliço-Silvestre6, F Fernández-Llimós4,5, IV Figueiredo1,2. 1Faculdade de Farmácia, Universidade de Coimbra, Grupo de Farmacologia e Cuidados Farmacêuticos, 3000-548 Coimbra, Portugal, 2Faculdade de Farmácia, Universidade de Coimbra, Centro de Estudos Farmacêuticos (CEF), 3000-548 Coimbra, Portugal, 3Hospitais da Universidade de Coimbra, Serviços Farmacêuticos, 3000-075 Coimbra, Portugal, 4Faculdade de Farmácia, Universidade de Lisboa, Departamento de Sócio-Farmácia, 1649-003 Lisboa, Portugal, 5Faculdade de Farmácia, Universidade de Lisboa, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), 1649-003 Lisboa, Portugal, 6Faculdade de Medicina, Universidade de Coimbra, Clínica Universitária de Infecciologia, 3000-548 Coimbra, Portugal

Introduction: Adverse effects (AE) associated to antiretroviral therapies are one of the main reasons for non-compliance, resistance to treatment and future therapeutic regimens modification.

The search of information in scientific literature about AEs prevention, identification and management, based on an evidence based approach, supports a better final clinical decision on individual patients. Search evidence, retrieved with focalized clinical question, can be assessed by the statistic parameters sensitivity and specificity, compared with a GOLD STANDARD group (GS).

Objective: Optimization of a systematic methodology to research clinical information on AE of antiretroviral therapy, developed in MEDLINE/PubMed, assessed by the relationship between sensitivity and specificity, having as reference a generic search strategy developed for searching information on drug iatrogenicity.

Methods: Construction of different search strategies, in three levels of increased complexity, using the special vocabulary Medical Subject Headings (MeSH), available in MEDLINE/PubMed, combined with indexing terms of three antiretroviral agents classes (fusion inhibitors, protease inhibitors, reverse transcriptase inhibitors), subheadings related to adverse effects, methodological filters related to the type of study (case reports, systematic reviews, randomized clinical trials), MeSH indexed keywords and subheadings related to clinical decision.

Statistical analysis was studied with the calculation of sensitivity and specificity values for the different search strategies. Sensitivity represents the percentage of articles retrieved by the search strategy that match the items belonging to the GS group and specificity represents the percentage of articles not retrieved by any search strategy neither belonging to the GS group.

Results: Characteristic adverse effects of antiretroviral agents were identified. Cutaneous hypersensitivity reactions for fusion inhibitors, lipodystrophy and hyperlipidemia for protease inhibitors and hepatotoxicity for reverse transcriptase inhibitors were the most adverse effects described in literature.

Sensitivity values were higher in the search strategies including case reports as the type of study. Its maximum value obtained was 77%. Specificity values increased according the type of study: case reports, systematic reviews, randomized clinical trials. Its maximum value obtained was 96,3%.

Conclusions: Statistic parameters show the importance of methodological filters related to the type of study, because information related to adverse effects associated to antiretroviral therapy was mainly found in case reports. It is reinforced the need for a better risk management of adverse clinical outcomes of antiretroviral therapy with more available information on scientific literature.