title: Maraviroc first-line therapy for HIV infection. Too risky.
abstract: First-line treatment for HIV infection currently comprises a combination of antiretroviral drugs, including a non-nucleoside reverse transcriptase inhibitor such as efavirenz, or one or two protease inhibitors.The choice is based on the results of initial clinical trials of antiretroviral drugs with morbidity and mortality endpoints, and, since the 1990s, on trials with surrogate markers (viral load and the CD4+ T lymphocyte count). Maraviroc is the only CCR5 antagonist currently on the market. Drugs belonging to this class are designed to prevent HIV entry into CD4 T lymphocytes. Maraviroc is reserved for patients with multiple treatment failure, but has also been proposed for first-line treatment. Clinical evaluation of maraviroc in first-line treatment is limited to a single comparative trial designed to show the virological and immunological "non-inferiority" of the maraviroc + zidovudine + lamivudine combination versus efavirenz + zidovudine + lamivudine, after 96 weeks of treatment, in 721 patients with CCR5-tropic HIV strains. A more sensitive version of the test used to determine CCR5 tropism became available during the trial, leading to the exclusion of 107 patients who were infected by strains capable of using other coreceptors. This trial fails to answer important questions regarding the adverse effects of maraviroc, such as hepatotoxicity, infections, cancer, and cardiovascular disorders. Tests used to identify exclusively CCR5-tropic HIV strains are difficult to implement and their results are unreliable. This means that some patients in whom maraviroc will not be effective may receive this drug, and will thus be at risk of developing viral resistance to other drugs in their antiretroviral regimen. In practice, first-line use of maraviroc is imprudent, as it depends on a test of uncertain reliability. Furthermore, there is no evidence to suggest that maraviroc combination therapy has a better risk-benefit balance than regimens with well-documented and long established efficacy.
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D000077592:Maraviroc; D012307:Risk Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D014230:Triazoles; D000077592:Maraviroc