Twenty years of boosting antiretroviral agents

Immediate Versus Deferred Switching From a Boosted Protease Inhibitor–based Regimen to a Dolutegravir-based Regimen in Virologically Suppressed Patients With High Cardiovascular Risk or Age ≥50 Years: Final 96-Week Results of the NEAT022 Study

“…Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) of the HIV-1 [1][2][3][4] generally well tolerated with a low potential for drug-drug interactions [5] , an infrequent emergence of resistance mutations [6] and a neutral lipid profile [7] . In antiretroviral naïve patients has demonstrated non-inferiority to raltegravir [8] and bictegravir [9,10] and superiority to efavirenz [11] and the ritonavir boosted darunavir [12] and atazanavir [13] .…”

“…Adverse events, all grades and causalities, were reported in 75% (weeks 0-48) and 77.9% (weeks 48-96) of the patients in the DTG-I arm and in 63.5% (weeks 0-48) and 83.8% (weeks 48-96) in the DTG-D arm of whom 6.4%,5.8% and 7.2% and 10.1% were SAE´s (p>0.05, table 2). 8 (3.9%) of patients who had received DTG in the DTG-I arm and 9 (4.5%) who had received DTG in the weeks 48-96 in the DTG-D arm vs. 3 (1.4%) of those who had received PI/r in the weeks 0-48 in the DTG-D arm interrupted study medication due to AE.…”

Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk

“…Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) of the HIV type 1 (HIV-1) [ 1 – 6 ]. DTG is a generally well tolerated [ 7 ] once daily drug, can be coformulated [ 8 ], has a low potential for drug–drug interactions [ 9 ], with infrequent emergence of resistance mutations when given as part of a combination regimen [ 10 – 13 ] and a neutral lipid profile [ 14 ]. In antiretroviral-naive patients, DTG has demonstrated noninferiority to raltegravir [ 15 , 16 ] and superiority to efavirenz [ 17 ] and the ritonavir-boosted protease inhibitors (PI/r) darunavir [ 18 ] and atazanavir [ 19 ].…”

“…Raltegravir, the first INSTI to be investigated in switch studies, resulted in significant lipid improvements while maintaining virological suppression in the Switching Protease Inhibitors to Raltegravir (SPIRAL) [ 5 ] study but not in the SWITCHMRK 1 and 2 studies [ 6 ]. Elvitegravir requires boosting with cobicistat so the issue of drug–drug interactions remains [ 9 , 31 ]. In the STRIIVING study [ 30 ], an unselected population of virologically suppressed HIV-1 infected patients were randomized to switch from their current regimen to a single tablet of DTG/abacavir/lamivudine or to continue with the current regimen.…”

The safety, tolerability, and pharmacokinetic profile of GSK2838232, a novel 2nd generation HIV maturation inhibitor, as assessed in healthy subjects

“…RTV (following steady‐state predosing with 100 mg QD) increased exposure (AUC and C max ) of GSK2838232 following a single dose by approximately 10‐fold and 3‐fold, respectively. The concept of pharmacokinetic boosting, where the metabolism of one drug is inhibited by another drug, is well‐documented with RTV and more recently cobicistat (both potent inhibitors of intestinal and hepatic CYP3A4 and P‐glycoprotein [P‐gp]) in order to improve the effectiveness and dosing convenience for anti‐HIV medications, especially HIV protease inhibitors . Systemic exposure of GSK2838232 was significantly increased by co‐administration with RTV, with the only metabolite detected in human plasma an O‐glucuronide.…”