The quad pill, a once-daily combination therapy for HIV infection.

Abstract

The quad pill is the newest single-pill, once-daily option for the treatment of human immunodeficiency virus (HIV) type 1 infection. In addition to tenofovir difumarate (TDF) and emtricitabine (FTC), the quad pill includes cobicistat (COBI; an inactivator of cytochrome P450 isoenzyme CYP3A without anti-HIV activity) and a new integrase inhibitor, elvitegravir (EVG). The quad does not have drug interactions with H2-receptor antagonists or proton pump inhibitors, does not cause central nervous system (CNS) side effects, and is pregnancy category B. It does have substantial drug interactions with medications that are metabolized using CYP3A and causes reversible declines in estimated glomerular filtration rate (eGFR) owing to inhibition of renal tubule transport of creatinine. In clinical trials, the virologic and immunologic efficacy of the quad pill is equivalent to that of other comparator regimens with low rates of discontinuation. The major side effect is nauseam which is self-limited, and the primary mutations associated with treatment failure frequently lead to cross-resistance with raltegravir (RAL).