Dolutegravir plus lamivudine for the treatment of HIV-1 infection

ABSTRACT

Introduction: Recent data on the 2-drug regimen (2DR) with dolutegravir (DTG) plus lamivudine (3TC) have shown high efficacy and tolerability both in treatment-naïve and experienced HIV-positive patients. Current guidelines recommend DTG+3TC as an alternative to triple antiretroviral therapy (ART) in selected patients to reduce long-term toxicity and costs.

Areas covered: This review is intended to provide insight about the efficacy, safety, and tolerability of a 2DR with DTG+3TC in naïve and treatment-experienced patients.

Expert opinion: Data from clinical trials and from real-life show that DTG+3TC is an effective and safe switch option for the treatment of experienced patients. In treatment-naïve patients, DTG+3TC has shown non-inferiority compared to standard 3-drug regimens but is less effective in severely immunocompromised naïve patients (i.e. with a CD4+ cell count below 200 cell/mm3); furthermore, current guidelines have upgraded this dual regimen to recommended first-line strategy, but indicate that it should not be used without genotypic resistance results. Moreover, this regimen is not feasible for HBV-coinfected individuals and should not be used during pregnancy. Currently, out of 2-drug regimens, DTG+3TC is one of clinicians’ preferred option as it requires no pharmacokinetic booster, has a low risk of drug interaction, and does not require food intake.

KEYWORDS:

• HIV
• dolutegravir
• lamivudine
• HAART
• 2-drug regimens

Article highlights

• Following recent evidence from clinical trials, DTG+3TC is the first dual regimen to be recommended as first-line treatment for HIV infection in patients with CD4+ cell count >200 cell/mm3, baseline HIV-RNA ≤500.000 copies/ml, negative HBsAg and no evidence of resistance mutations;

• Several observational studies and clinical trials explored the efficacy and safety of DTG+3TC as a switch strategy, concluding that it represents an attractive option in virological suppressed patients;

• DTG+3TC presents a favorable effect on blood lipid profile, low risk of drug interactions and a potential benefit on bone mineral density;

• Issues on DTG discontinuations due to neuropsychiatric events and body weight increase need further studies to be assessed;

• Overall, treatment failure rates with DTG+3TC are low and there are scarce reports of the incidence of resistance mutations at failure, confirming the high genetic barrier of this regimen and its safety.

Declarations of interest

S Di Giambenedetto has received fees from Gilead sciences, ViiV, BMS, Merck Sharpe & Dohme, and Janssen. A Borghetti has received personal fees from Gilead sciences and non-financial support from BMS and ViiV. 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

A reviewer on this manuscript was an investigator on the PADDLE study. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.