Abstract
During the last 30 years, antiretroviral treatment (ART) for human immunodeficiency virus (HIV) infection has been continuously evolving. Since 1996, three-drug regimens (3DR) have been standard-of-care for HIV treatment and are based on a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The effectiveness of first-generation 3DRs allowed a dramatic increase in the life expectancy of HIV-infected patients, although it was associated with several side effects and ART-related toxicities. The development of novel two-drug regimens (2DRs) started in the mid-2000s in order to minimize side effects, reduce drug–drug interactions and improve treatment compliance. Several clinical trials compared 2DRs and 3DRs in treatment-naïve and treatment-experienced patients and showed the non-inferiority of 2DRs in terms of efficacy, which led to 2DRs being used as first-line treatment in several clinical scenarios, according to HIV clinical guidelines. In this review, we summarize the current evidence, research gaps and future prospects of 2DRs.
Highlights
Three-drug regimens (3DRs) became the main treatment for human immunodeficiency virus (HIV) infection in 1996, dramatically increasing the life expectancy of HIV-infected patients and lowering the number of acquired immunodeficiency syndrome (AIDS) events
Two-drug regimens based on two nucleoside reverse transcriptase inhibitor (NNRTI) have not been able to demonstrate noninferiority compared to 3DR
The 2NN Study was an open-label clinical trial evaluating the combination of two first-generation NNRTIs, efavirenz (EFV) plus nevirapine (NVP)
Summary
Three-drug regimens (3DRs) became the main treatment for HIV infection in 1996, dramatically increasing the life expectancy of HIV-infected patients and lowering the number of acquired immunodeficiency syndrome (AIDS) events. Substituting TDF for TAF as a backbone is related to an improvement in renal function (i.e., creatinine clearance) and bone mineral density [14], and a pooled analysis of 26 clinical trials comprising more than 9300 patients reported a lower rate of proximal renal tubulopathy (0.34% vs 0%) and discontinuations due to renal adverse events (0.47% vs 0.05%) in patients who received. Second-generation boosted PIs became the mainstay of many 2DR clinical trials due to their high genetic barrier for the development of drug resistance. Most of these studies included lamivudine (3TC), a second generation of NRTI with a good safety and efficacy profile, as the companion drug.
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