So with all the positive news about integrase inhibitors in initial HIV treatment, is it safe to switch patients from other NNRTI (non-nucleoside reverse transcriptase inhibitor)- or PI (protease inhibitor)-based regimens to integrase inhibitor regimens? Our previous lesson from the SWITCHMRK and SPIRAL studies reminds us to be cautious, particularly when switching drug-resistant patients receiving a boosted PI (lopinavir).
The open-label STRATEGY studies -- incredibly accepted only as poster presentations despite reporting the final results of nearly 900 patients in phase-3 studies -- presented at CROI 2014 learned this lesson by restricting participants to patients on first- or second-line treatment regimens with no previous virologic failure.
In these well-powered studies, patients were randomized 2:1 to switch to elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) or continue stable NNRTI or PI regimens. Patients with an eGFR (estimated glomerular filtration rate -- one method for assessing kidney health) greater than 70 were excluded.
Overall, switching to elvitegravir/cobicistat/emtricitabine/tenofovir from NNRTIs (78% efavirenz [Sustiva, Stocrin], 17% nevirapine [Viramune]) was non-inferior, while switching from boosted PIs (40% darunavir [Prezista]/ritonavir [Norvir], 40% atazanavir [Reyataz]/ritonavir) showed statistical superiority over elvitegravir/cobicistat/emtricitabine/tenofovir.
Virologic failure was rare in all study arms and no resistance was selected at failure in any participants treated with elvitegravir/cobicistat/emtricitabine/tenofovir. Not surprisingly, neuropsychiatric symptoms improved after switching off efavirenz, lipid values improved following switching from lopinavir/ritonavir (Kaletra), and gastrointestinal symptoms improved after PI switch.
While these open-label studies have inherent limitations by virtue of their design, the implications are clear: In patients without viral drug resistance, switching from NNRTI- or PI-based treatment to elvitegravir/cobicistat/emtricitabine/tenofovir appears safe and may result in desired improvements in symptoms or toxicity. Will these lessons extend to switches to other integrase inhibitors? Quite probably, though this remains a largely data-free area yet with dolutegravir (Tivicay, DTG).
Which other studies presented at CROI 2014 will have lasting impact? Read more of Dr. Llibre and Dr. Young's top picks.