Combination Therapy with Tenofovir Disoproxil Fumarate/Emtricitabine/Elvitegravir/Cobicistat Plus Darunavir Once Daily in Antiretroviral-Naive and Treatment-Experienced Patients: A Retrospective Review

Abstract

Background: : Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir-disoproxil-fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/ cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA <40 copies/mL at 48 weeks. Methods: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV. Results: Among the 21 included patients, prior resistance showed a median of 2 nucleoside reverse transcriptase inhibitor mutations, 1 nonnucleoside reverse transcriptase mutation, and 1 protease inhibitor mutation. At week 48, 14 (67%) patients achieved HIV-1 RNA <40 copies/mL, 1 patient experienced viral rebound, and 6 (29%) had missing data or discontinued therapy. No patient discontinued for adverse events. Conclusion: According to this observational study, QD TDF/FTC/EVG/cobi plus DRV is considered safe, well tolerated, and generally effective in suppressing HIV drug-resistant virus.

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study

“…Regarding real-world data, the evidence for the effectiveness of this regimen is very limited: only three cohort studies have been published analysing EVG/COB/TDF/ FTC + DRV, all from single centres, involving a very low number of patients, and analysing different endpoints. The effectiveness was high in the three studies: Naccarato et al evaluated 21 treatment-experienced patients (29% of which were virologically suppressed before the switch) who received EVG/COB/TDF/FTC + DRV: at week 48, 14 (67%) patients had undetectable viral load, 1 had virologic failure (> 40 copies/ml) and 6 had stopped the treatment or had no viral load data [5]. Harris et al evaluated the simplification to the same regimen in 10 virologically suppressed patients: 8 of them had viral loads < 40 copies/ml at weeks 24 and 48 and all of them had viral loads < 200 copies/ml up to week 48 [6].…”

“…4 Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain. 5 Hospital Universitario Ramón y Cajal, Madrid, Spain. 6 Corporació Sanitària Parc Taulí, Barcelona, Spain.…”

“…With these combinations, COB, which boosts EVG, would also allow boosting of DRV [5]. However, pharmacokinetic studies evaluating drug levels in patients receiving EVG/COB/TDF/FTC plus DRV have found conflicting results.…”

“…However, in spite of the results of this clinical trial and the potential advantages of this combination for ART simplification, there is very little evidence in real-life clinical practice. Only three single-centre cohort studies analysing EVG/COB/TDF/FTC + DRV have been published, involving a very low number of patients (21, 10, and 17 patients) and with limited follow-up [5,6,11].…”

Recent Advances in the Discovery of Small-Molecule Inhibitors of HIV-1 Integrase

“…It possesses potent inhibitory activity with an IC 50 of 7.2 nM in the ST assay, and shows an EC 50 of 0.9 nM in an acute HIV-1 infection assay [ 66 , 67 ]. Clinical trials showed that the Genvoya regime was very effective in reducing viral load (plasma HIV-1 RNA levels) to less than 40 copies/ml at the week 48 assessment, and displayed durable suppression of viral load to less than 50 copies/ml for up to 6 months [ 68 ]. The discovery of EVG and the development of Genvoya brought in an important advance with once-daily single-tablet regime for the effective treatment of HIV-1 infection.…”