Current and emerging two-drug approaches for HIV-1 therapy in ART-naïve and ART-experienced, virologically suppressed patients

ABSTRACT

Introduction: Current guidelines recommend a 2-drug antiretroviral regimen 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 into the efficacy, safety and tolerability of 2-drug versus 3-drug ART in naïve and in treatment-experienced virologically-suppressed patients.

Expert opinion: Dual therapy regimens are not feasible in HBV-coinfected individuals and should not be applied during pregnancy. Positive data on 2-drug ART in drug naïve patients are still limited, while, in virologically-suppressed individuals, several regimens have shown non-inferiority as compared to 3-drug regimens. The strongest evidence of efficacy applies to ritonavir-boosted PI regimens combined with lamivudine and to dolutegravir with rilpivirine. Dual therapies showed improved renal function and bone mineral density over tenofovir disoproxil fumarate-based 3-drug regimens. There are also great expectations for ongoing phase 3 trials testing dolutegravir with lamivudine. New and future single tablet co-formulations of dual regimens are expected to improve their suitability. Despite the lack of comparison with tenofovir alafenamide-based 3-drug regimens, the 2-drug regimens showing consistent non-inferiority and safety versus 3-drug regimens will challenge the current paradigm of 3-drug ART.

KEYWORDS:

• HIV-1
• antiretroviral therapy
• less drug regimen
• dual therapy
• simplification
• switch therapy

Article highlights

• Combination antiretroviral therapy with 3 drugs currently represents the mainstay of HIV therapy

• Long-term exposure to antiretroviral drugs has been associated with several toxicities

• Evidence of efficacy and safety of dual therapy in ART-naïve patients is still limited

• Dual regimens with boosted protease inhibitors and lamivudine are non-inferior and show reduced renal or bone toxicity as compared to 3-drug regimens with protease inhibitors in virologically suppressed patients

• Switching to a selected dual regimens may help to reduce side effects and costs

• Dolutegravir with rilpivirine is non-inferior to continuing 3-drug regimens and shows improvement of bone mineral density in virologically suppressed patients. This regimen is now available as a single tablet and represents a valid treatment switch option.

• Dolutegravir with lamivudine has shown encouraging results in prospective non-controlled and retrospective studies, as first-line therapy and in the switch settting. If results of phase 3 randomized studies in naïve patients will confirm these findings, this regimen will eventually be co-formulated and will challenge the current paradigm of 3-drug therapy.

• The toxicity advantages (renal, bone) of 2-drug versus 3-drug therapies have been verified against 3-drug regimens containing tenofovir disoproxil; no comparison has yet been performed against tenofovir alafenamide-containing 3-drug regimens, which show considerably less renal and bone toxicity.

This box summarizes key points contained in the article.

Declaration of Interest

A De Luca received research grants via his institutions from ViiV Healthcare, Gilead Sciences (through a fellowship program) and Merck Sharp and Dohme, Italy. They have also received consultancy fees from ViiV Healthcare, Gilead Sciences, Merck Sharp and Dohme, Italy, Janssen Pharmaceuticals, Bristol-Myers Squibb and AbbVie. B Rossetti has received support for attending conferences from Janssen Pharmaceuticals, Gilead Sciences, ViiV Healthcare and from AbbVie in addition to personal fees from Merck Sharp and Dohme. F Montagnani has received support for conference attendance from Angelini and Astellas. She has also performed research for Novartis Vaccine and Diagnostic S.r.l. (now GlaxoSmithKline Vaccine S.r.l) on behalf of the University of Hospital of Siena. She is also an infectious diseases consultant for GlaxoSmithKline and receives a consultancy fee on behalf of the University of Siena. 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. One referee declares that they’ve received research grants from Gilead Sciences and Merck & Co. Furthermore, they declare that they’ve received honoraria for contract work performed for Gilead Sciences, Janssen-Cilag, Merck & Co., and ViiV Healthcare.

Additional information

Funding

This manuscript has not been funded.