Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter observational study

Abstract

BackgroundAim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT).MethodsObservational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis.ResultsOverall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity.ConclusionsIn our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.

Efficacy and durability of two‐ vs. three‐drug integrase inhibitor‐based regimens in virologically suppressed HIV‐infected patients: Data from real‐life ODOACRE cohort

“…In the last few years, the use of 2DRs has gradually taken place as a novel paradigm for the treatment of HIV infection. Initially, 2DRs have become feasible due to the availability of last-generation boosted PIs, which are characterized by a high potency and genetic barrier; several trials and studies from clinical practice have demonstrated the efficacy and durability of 2DRs based on a PI plus a second drug for the treatment of HIV infection [37][38][39][40][41][42]. The advent of InSTIs, which are characterized by improved tolerability relative to PIs, has prompted researchers to evaluate the efficacy of InSTI-based 2DRs, especially those including dolutegravir, a second-generation InSTI with a high genetic barrier.…”

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

“…None of the trials of two‐drug combinations have studied the effect of treatment simplification on HIV tissue reservoirs. Only one has looked at the effect of treatment simplification on blood reservoirs in terms of total HIV DNA, although measurements of the replication competent reservoir would have been more relevant .…”

Taxa de descontinuação da terapia antirretroviral dupla com dolutegravir mais lamivudina em pessoas vivendo com HIV: uma revisão sistemática

“…Com o desenvolvimento de inibidores de integrase mais potentes, houve um aumento do número de estudos que avaliam o uso da terapia dupla em pessoas vivendo com HIV, os quais têm demonstrado efetividade da terapia dupla na manutenção da carga viral indetectável (Mondi et al, 2015;Latini et al, 2016;Fabbiani et al, 2016;Perez-Molina et al, 2017;Pulido et al, 2017;Fabbiani et al, 2018). Contudo, os eventos adversos provocados pelo consumo desses medicamentos são uma das maiores causas de descontinuação do tratamento.…”