Two‐drug vs. three‐drug combinations for HIV‐1: Do we have enough data to make the switch?

Abstract

Three‐drug combination antiretroviral therapy (ART) became available in 1996, dramatically improving the prognosis of people living with HIV. The clinical benefits of ART are due to the sustained viral load suppression and CD4 T cell gains. Major drawbacks of the first ART regimens were adverse events, and high pill burden, which led to the reduction of drug adherence resulting in frequent treatment discontinuations and the development of drug resistance. Due to increased viral potency of new antiretroviral drugs consideration of a two‐drug combination therapy repositioning occurred in an effort to reduce adverse events, drug‐drug interactions and cost, while maintaining a sustained antiviral effect. Various combinations of two‐drug regimens have been studied, and non‐inferiority compared to a three‐drug regimen has been shown only for some of them. In addition, a two‐drug combination regimen may not be suitable for every patient, especially those who are pregnant, those with tuberculosis or coexisting HBV infection. Furthermore no information has been generated concerning the secondary transmission of HIV from patients who have undetectable plasma viral load on two‐drug regimens. Additional studies of two‐drug combinations are also necessary to evaluate the debated existence of low viral replication in tissues and on immune activation. While there is no urgent need to routinely switch patients to two‐drug combination therapy, due to the availability of drug combinations without significant toxicities, dual regimens represent a suitable option that deserve long‐term evaluation before being introduced to clinical practice.

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single‐tablet regimen in the expanding spectrum of fixed‐dose combination therapy for HIV

“…There is increasing evidence that two‐drug regimens, such as DTG plus 3TC, may lead to equally good outcomes provided there is no active hepatitis B, underlying significant HIV genotypic resistance, CD4 count < 200 cells/mL, viral load> 500 K or a pregnancy risk . Other two‐drug regimens are also available for maintenance cART, including long‐acting parenteral CAB/RPV and oral co‐formulated DTG/RPV .…”

Two‐drug antiretroviral regimens: an assessment of virologic response and durability among treatment‐experienced persons living with HIV in the OPERA® Observational Database

“…There is a growing body of clinical trial evidence that 2‐DRs may be effective in maintaining virologic suppression among treatment‐experienced patients . 2‐DRs containing ritonavir‐boosted PIs or integrase strand transfer inhibitors (INSTI) have been most promising .…”

“…Several systematic reviews and meta‐analyses of trials assessing the efficacy and safety of 2‐DRs have found comparable efficacy to standard 3‐DRs, especially among suppressed, treatment‐experienced patients with PI‐and INSTI‐based regimens . Punekar et al .…”

Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

“…Moreover, many combination therapies, which include BSAAs, became a standard for the treatment of HIV and HCV infections. These include abacavir/dolutegravir/lamivudine (Triumeq), darunavir/cobicistat/emtricitabine/tenofovir (Symtuza), lopinavir/ritonavir (Kaletra), ledipasvir/sofosbuvir and sofosbuvir/velpatasvir (98)(99)(100).…”