Comparative safety review of recommended, first-line single-tablet regimens in patients with HIV

ABSTRACT

Introduction Different single-tablet regimens (STRs), containing one or two nucleoside reverse transcriptase inhibitors (NRTIs) plus an anchor drug, are available for the use in naïve, HIV-infected patients. Despite some restrictions in the use of particular regimens in certain situations (e.g., HBV coinfection), International guidelines do not provide indications to prefer any regimen over others concerning the tolerability profile. We aimed to assess advantages and disadvantages of the most prescribed STRs.

Areas covered An extensive review of articles published in English language was conducted on PubMed, looking for evidence about STRs in naïve, HIV-infected population. Safety outcomes of registrational trials were assessed, giving priority to studies directly comparing STRs included in our research (abacavir/lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/bictegravir, lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/darunavir/cobicistat, tenovofir disoproxil fumarate/lamivudine/doravirine). Data from cohort studies and meta-analyses were also assessed, extrapolating the main evidence about the combinations of interest.

Expert opinion Integrase inhibitors (InsTIs)-based regimens have few interruptions for adverse events and few drug-related adverse events, with tenofovir alafenamide/emtricitabine/dolutegravir and lamivudine/dolutegravir being the most tolerable ones. However, neuropsychiatric adverse events and metabolic issues could prompt the alternative use of darunavir or doravirine-based combinations, even if a superior safety profile of these combinations over InSTIs has yet to be demonstrated.

KEYWORDS:

• HIV
• naive
• review
• safety
• single tablet-regimens

Article highlights

• Several single tablets regimens (STRs) are available for the treatment of naïve, HIV-positive patients;

• Comparison of tolerability profiles of the recommended strategies is lacking;

• Integrase inhibitors (InSTIs) dolutegravir and bictegravir are the mainstay of HIV-treatment for both their efficacy and safety profiles;

• Concerns have emerged with InSTIs regarding their neuropsychiatric tolerability and metabolic profile;

• Doravirine and Darunavir-based STRs seem to have good safety profile, but they lack of direct comparison with InSTIs.

Declaration of interest

A Borghetti has received grants from ViiV Healthcare and Janssen-Cilag. S Di Giambenedetto has received grants from Bristol-Myers Squibb, non-financial support from Bristol-Myers Squibb, and personal fees from Bristol-Myers Squibb, Gilead Sciences, Abbott, Boehringer Ingelheim, Janssen-Cilag, ViiV and GlaxoSmithKline. 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 work has been performed with internal funding.