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      Two’s a Company, Three’s a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1

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          Abstract

          Introduction

          As HIV has become a manageable chronic condition, a renewed and increased interest in challenging traditional three-drug HIV therapies and moving toward two-drug regimens (2DR) for initial or maintenance treatment in people living with HIV (PLWH) has developed. As PLWH are living longer, continual advancements in antiretroviral regimens have been a focus to provide optimal life-long therapy options. Although early studies may have shown poor outcomes in virologic suppression with 2DR, newer studies and treatment options have emerged to show promise in the management of HIV. The purpose of this review is to evaluate current literature and assess the efficacy of two-drug (2DR) antiretroviral therapy in treatment-naïve and -experienced people living with HIV.

          Methods

          A systematic search was performed between January 2009 to January 2020, using EMBASE, MEDLINE, Google Scholar, and bibliographies. Combinations of the following search terms were used: HIV-1 infection, antiretroviral therapy, dual therapy, two-drug regimen, two-drug therapy, two-drug regimen, and 2DR. Included studies were those in the adult population with at least one active comparator, outcomes assessing HIV-1 RNA viral load while on treatment, and written in English.

          Results

          Thirty-three studies were included, 13 where 2DRs were evaluated as initial therapy (3 studies with extension data) and 15 where 2DRs were evaluated as maintenance or switch therapy (2 studies with extension data).

          Conclusion

          Although 2DRs may not be appropriate in all patient populations, they are being utilized more frequently and have the potential to reduce costs, adverse effects, and drug interactions.

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          Most cited references36

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          Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

          Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks.
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            Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies

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              The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic.

              In the last 25 years, HIV-1, the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), has gone from being an "inherently untreatable" infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including (1) the life-long duration of therapy; (2) the ultimate role of pre-exposure prophylaxis (PrEP); (3) the cardiometabolic side-effects or other toxicities of long-term therapy; (4) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); (5) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and (6) the continued pace of new HIV-1 infections in many parts of the world. All of these factors make refining current therapies and developing new therapeutic paradigms essential priorities, topics covered in articles within this special issue of Antiviral Research. Fortunately, there are exciting new insights into the biology of HIV-1, its interaction with cellular resistance factors, and novel points of attack for future therapies. Moreover, it is a short journey from basic research to public health benefit around the world. The current science will lead to new therapeutic strategies with far-reaching implications in the HIV-1/AIDS pandemic. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                badowski@uic.edu
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                19 March 2020
                19 March 2020
                June 2020
                : 9
                : 2
                : 185-208
                Affiliations
                [1 ]GRID grid.185648.6, ISNI 0000 0001 2175 0319, College of Pharmacy, , University of Illinois, ; Chicago, IL USA
                [2 ]GRID grid.266832.b, ISNI 0000 0001 2188 8502, College of Pharmacy, , University of New Mexico, ; Albuquerque, NM USA
                Article
                290
                10.1007/s40121-020-00290-w
                7237600
                32193799
                a76f1c9c-5d48-4a56-afaa-dd19eb321868
                © The Author(s) 2020
                History
                : 27 January 2020
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                antiretroviral therapy,dual therapy,hiv,hiv treatment,two-drug regimen (2dr)

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