The New Booster on the Block: A Review of Cobicistat in HIV Therapy

CDC: New HIV Pre-Exposure Prophylaxis Guidelines
CDC: New HIV Pre-Exposure Prophylaxis Guidelines
Cobicistat, a pharmacokinetic (PK) enhancer without antiviral activity, is a relatively new HIV drug booster.

An estimated 35.3 million people worldwide and 1.2 million people in the U.S. are living with HIV-1.2 Treatment of HIV patients in the U.S. is directed by guidelines produced by The Department of Health and Human Services (DHHS). Combination antiretroviral therapy (ART) has been shown to decrease both morbidity and mortality in HIV patients.3 A variety of ART drugs have been developed, with six different mechanisms, including the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), a fusion inhibitor (FI), a CCR5 antagonist, and integrase strand transfer inhibitors (INSTIs). Pharmacokinetic (PK) enhancers or boosters are used to improve the pharmacokinetic profiles of some ART drugs.  Initial ART for treatment-naïve patients typically include two NRTIs with an INSTI, NNRTI, or a PK-boosted PI. With these treatments, HIV has become a chronic, manageable disease.

Treatment regimens are selected based on factors such as expected side effects, convenience, comorbidities, and drug interactions with concomitant medications from pretreatment genotypic testing. INSTI-based regimens are preferred because of their efficacy, safety and tolerability, and lower number of drug-drug interactions. A PK-boosted PI treatment is preferred in patients with poor adherence or those who have transmitted NRTI drug resistance because PIs have a higher genetic barrier to resistance.

HIV therapies are always improving to provide patients with newer, effective treatments utilizing combinations of drug classes. Cobicistat, a pharmacokinetic (PK) enhancer without antiviral activity, is a relatively new HIV drug booster. It exerts selective cytochrome P450 (CYP) 3A inhibition against the metabolism of certain antiretrovirals which increases systemic exposure of these drugs. Cobicistat was developed as an alternative to ritonavir due to the associated adverse events with short- and long-term retroviral (RTV) use, such as gastrointestinal intolerability, drug-drug interactions, insulin resistance, lipodystrophy, and hyperlipidemia.1 Phase 3 studies have demonstrated its tolerability, noninferiority, and bioequivalence to ritonavir, proving to be a promising alternative for HIV treatment options.  However, its effect on serum creatinine and potential for drug interactions may require additional monitoring.