Pharmacokinetic drug evaluation of ritonavir (versus cobicistat) as adjunctive therapy in the treatment of HIV

ABSTRACT

Introduction: Ritonavir and cobicistat are pharmacoenhancers used to improve the disposition of other HIV antiretrovirals. These drugs are, however, characterized by important pharmacokinetic differences.

Areas covered: Here, the authors firstly update the available information on the pharmacokinetics of ritonavir and cobicistat. Subsequently, the review focuses on the description of drug-drug interactions (DDIs) involving cobicistat and comedications that might beneficiate from a shift-back to ritonavir. A MEDLINE Pubmed search for articles published from January 1995 to April 2019 was completed matching the term ritonavir or cobicistat with pharmacokinetics, DDIs, and pharmacology. Moreover, additional studies were identified from the reference list of retrieved articles.

Expert opinion: Despite more than 20 years after its introduction on the market, ritonavir still represents a valid option for the treatment of selected HIV-infected patients. The large-scale switch to cobicistat may result in some unexpected DDIs not previously reported for ritonavir. Besides the issue of DDIs, additional advantage of ritonavir over cobicistat is its use in pregnancy, and its availability as single component of pharmaceutical formulations allowing the fine-tuning of antiretroviral regimens in patients with heavy polypharmacy when other unboosted-based therapeutic options cannot be used.

KEYWORDS:

• Drug-drug interactions
• HIV
• ritonavir
• cobicistat
• pharmacokinetics
• polypharmacy

Article highlights

• Ritonavir has a linear pharmacokinetics minimally affected by food. No dose adjustments are required in patients with renal or hepatic insufficiency. The drug is a potent inhibitor of CYP3A, CYP2D6 and an inducer of CYP2B6 and UGT.

• Cobicistat is a structural analogue of ritonavir without antiviral activity. The pharmacokinetics of cobicistat is not linear, and is not affected by food. No dose adjustment is required in patients with mild-to-moderate renal or hepatic insufficiency (the use of this drug is discouraged in patients with hepatic impairment Child-Pugh Class C). The drug is a potent inhibitor of CYP3A and has no inducing activity on metabolic enzymes or drug transporters.

• No different effects of ritonavir over cobicistat are expected when the two boosters are switched each other in HIV-infected patients concomitantly treated with CYP3A substrates. Conversely, DDIs may take place in patients concomitantly treated with CYP2D6, CYP2B6 or UGT substrates.

Advantages of ritonavir over cobicistat are its use in pregnancy and its availability as a single component of pharmaceutical formulations allowing the fine-tuning of antiretroviral regimens in patients with heavy polypharmacy (in most countries cobicistat is available only co-formulated with other antiretrovirals).

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Declaration of interest

D Cattaneo declares receiving speaker fees from ViiV Healthcare, Janssen Cilag, Merk, and Angelini. G Rizzardini declares receiving speaker fees from ViiV Healthcare, Janssen Cilag, Merk, Angelini, and Abbvie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.