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New and Pipeline Antiretroviral Agents for the Treatment of HIV-1 Infection

It is clear that effective antiretroviral therapy (ART), when taken consistently, can reduce morbidity and mortality among persons infected with human immunodeficiency virus (HIV) and significantly lowers the risk of sexual transmission to HIV-negative partners. Given the complexities of ART, such as patient adherence, side effects, toxicities, allergies, drug-drug interactions, restricted drug formularies, socioeconomic factors and the prevalence of resistance mutations, developing new drugs and new classes for the treatment of HIV is paramount. There are several new ART formulations in various stages of development, some with novel mechanisms of action and routes of administration, being investigated for the treatment of HIV-1, pre-exposure prophylaxis (PrEP) and HIV cure. Clinicians should be cognizant of new and pipeline ART drugs, formulations and combinations, in order to reach the goals of complete virologic suppression and improved clinical outcomes in persons living with HIV (PLWH). Newly-approved agents, and drug combinations in development, should be safe, well-tolerated, long-lasting and affordable, with minimal pill burden to optimize adherence. 
Several studies have shown that combination antiretroviral therapy (ART) can reduce morbidity and mortality for those infected with human immunodeficiency virus (HIV).1,2 When treating people living with HIV (PLWH) and acquired immune deficiency syndrome (AIDS), the goal is consistent and long-term virologic suppression, allowing CD4+ T-cell counts to rise with a commensurate reduction in the risk of opportunistic infections, HIV-associated nephropathy (HIVAN),3 AIDS-related malignancies, cardiovascular disease4,5  and other HIV-related morbidities. It is clear that full virologic suppression can reduce transmission to HIV-negative sexual partners, as well.6-8 It is therefore vital to choose an ART regimen that is safe and well-tolerated, minimizing the potential for adverse effects, toxicities, and drug-drug interactions. The clinician must also consider the results of genotype testing, baseline HIV viral load, baseline CD4+ T cell count, human leukocyte antigen (HLA)-B*5701 status, pill burden, allergies, comorbid conditions, history of ART adherence, and socioeconomic factors in each individual. 

Given the potential complexities of ART administration, a desire to consolidate regimens to minimize pill burden, and the prevalence of HIV-1 resistance mutations, new combination therapies are available – and in the pipeline – to maximize the likelihood of adherence and virologic suppression. The worldwide burden of HIV/AIDS, about 37 million individuals as of 2014,9 heightens the urgency of increasing the proportion of PLWH on effective treatment. Indeed, poor adherence to medications used for chronic diseases, such as HIV, is relatively common, particularly when there is a necessity for a large pill burden or pleonastic dosing frequency.10 This makes it all the more critical to consolidate therapy and minimize side effects. Recent advances in ART medication formulations, such as single-pill complete ART and long-acting injectable agents, are making it easier for PLWH to be adherent, and for the clinician to construct somewhat simple salvage regimens for those with multiple significant resistance mutations. This article seeks to review newer ART agents, as well as those in later stages of drug development, for the treatment of HIV-1 infection.

Is there a cure? How long until we find it? And will it work for the majority of people living with HIV?