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The use of single-tablet regimens (STRs) as initial antiretroviral therapy has become highly popular, and the number of such options continues to expand. The first STR combination, efavirenz/tenofovir/FTC, has been widely used but has a relatively high rate of central nervous system (CNS) side effects, prompting interest in alternatives. The more recently approved rilpivirine/tenofovir/FTC combination has demonstrated comparable efficacy in study participants with baseline HIV RNA levels ≤100,000 copies/mL and appears to have significantly fewer side effects, especially CNS side effects. However, switching from efavirenz to rilpivirine might be problematic: Because the effect of efavirenz as an inducer of the cytochrome P450 3A4 enzyme (a m…