title: Rilpivirine. First-line treatment of HIV infection: efavirenz is better documented.
abstract: In previously untreated HIV-1 infection, one first-line therapeutic option is to combine efavirenz, a non-nucleoside reverse transcriptase inhibitor, with tenofovir and emtricitabine. Rilpivirine, another non-nucleoside reverse transcriptase inhibitor, has been approved in the European Union for the treatment of antiretroviral-naive patients with low viral load. Two double-blind "non-inferiority" trials compared rilpivirine- and efavirenz-based combination therapy in a total of 1368 previously untreated patients. Efficacy was similar with respect to the primary endpoint: 80% of patients had viral load below 50 copies/ml after 48 weeks of treatment. In these trials, combinations containing rilpivirine appeared less effective than those containing efavirenz in patients with high viral load (above 100 000 copies/ml). Overall, the risk of virological failure appeared to be higher with rilpivirine than with efavirenz (20.4% versus 18% after 196 weeks). In addition, the potential for cross-resistance to other non-nucleoside reverse transcriptase inhibitors in case of virological failure appeared to be higher with rilpivirine than with efavirenz. Compared with the known adverse effect profile of efavirenz, rilpivirine was associated with less rash (17% versus 31%) and dizziness (10% versus 29%). The incidence of depression appeared similar with the two drugs. In contrast, serum creatinine elevation was more frequent with rilpivirine (5% versus < 1%). Gallstones and adrenal insufficiency are also likely to be more frequent with rilpivirine. High doses of rilpivirine prolong the QTc interval. Rilpivirine carries a risk of pharmacokinetic interactions with many other drugs, including inducers and inhibitors of cytochrome P450 isoenzyme CYP3A4, drugs that increase gastric pH, and drugs transported by P-glycoprotein. Rilpivirine also carries a high risk of pharmacodynamic interactions, notably with drugs that prolong the QTc interval. In practice, as rilpivirine has no proven therapeutic advantages, when combination therapy containing a nonnucleotide reverse transcriptase inhibitor is chosen for previously untreated patients, it is better to continue to use efavirenz, a better-known drug that creates fewer problems in case of treatment failure.
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D009570:Nitriles / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000068696:Rilpivirine; D019562:Viral Load
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine; C098320:efavirenz