Drug–drug interactions of a two-drug regimen of dolutegravir and lamivudine for HIV treatment

ABSTRACT

Introduction: The GEMINI trials have recently shown that a two-drug regimen of dolutegravir plus lamivudine was non-inferior to a three-drug regimen in HIV-infected naïve patients. Accordingly, it is important that physicians be aware and confident about the drug–drug interactions (DDIs) involving dolutegravir, lamivudine, and other medications.

Areas covered: Here, we firstly update the available information on the pharmacokinetic features of dolutegravir and lamivudine; subsequently, the articles mainly deals with the predictable DDIs for both antiretroviral drugs, attempting to underline their clinical implications. This review focuses on the DDIs of dolutegravir/lamivudine combined regimen and, therefore, does not provide an exhaustive list of all the potential DDIs involving the two single agents. A MEDLINE Pubmed search for articles published from January 2000 to December 2018 was completed matching the terms dolutegravir or lamivudine with pharmacokinetics, DDIs, and pharmacology. Moreover, additional studies were identified from the reference list of retrieved articles.

Expert opinion: The antiretroviral dual regimen of dolutegravir and lamivudine represents an attractive therapeutic option for HIV in terms of DDIs. This is particularly relevant considering that the population with HIV is aging and is increasingly experience age-related comorbidities, increasing pill burden, polypharmacy and the risk of DDIs.

KEYWORDS:

• Drug-drug interactions
• HIV
• dolutegravir
• lamivudine
• pharmacology

Article highlights

• The GEMINI trials have recently shown that a two-drug regimen of dolutegravir plus lamivudine was non-inferior to a three-drug regimen of dolutegravir and tenofovir disoproxil fumarate/emtricitabine in HIV-infected naïve patients, providing a rationale for the treatment of selected naïve patients with dual antiretroviral regimens.

• The clinically relevant DDIs involving dolutegravir as the victim is largely expected (related mainly to the known effects of metabolic enzyme inducers) and easily manageable in the daily practice by doubling drug dose. The few DDIs involving dolutegravir as potential perpetrator are actually of very limited clinical relevance.

• Lamivudine has lower propensity to suffer or to cause clinically relevant DDIs than dolutegravir. Indeed, the few DDIs reported to date involve very little use drugs, such as trimethoprim.

• The population with HIV is aging, thus increasing the frequency of age-related comorbidities, pill burden, polypharmacy and the risk of DDIs. Accordingly, it is desirable that the awareness of the growing risk of DDIs in the aging HIV patient may favor a rationalization of therapies as a whole, including drugs given to treat comorbidities.

This box summarizes key points contained in the article.

Declaration of interest

G Rizzardini has received speaking fees from MSD, ViiV, Gilead, and AbbVie. D Cattaneo has received speaking fees from ViiV, MSD, and Janssen. A Capetti has received speaking fees from ViiV, Gilead, and MSD. 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 apart from those disclosed.

Reviewer Disclosures

One peer reviewer has carried out consulting work for Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare; has received compensation for lectures from Abbvie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck,<br>and ViiV Healthcare, as well as grants and payments for the development of educational presentations for Gilead Sciences and Bristol-Myers Squibb. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.