Antiretroviral therapy with integrase inhibitors: more options

Strand transfer inhibitors of HIV-1 integrase represent a new and very potent class of compounds, besides reverse transcriptase and protease inhibitors. The first integrase inhibitor, raltegravir, was made available in 2007. Recently, phase 3 studies of two new compounds - elvitegravir which needs pharmacological boosting with either ritonavir or cobicistat, and dolutegravir - have been presented, showing high virologic success rates, over 48-96 weeks, both in first-line antiretroviral therapy and in the treatment of experienced patients. The clinical tolerance of the three inhibitors is good, and they have globally a good safety profile. Dolutegravir and cobicistat exerts a blockade of the renal tubular secretion of creatinine, leading to a decrease in estimated creatinine clearance, which does not reflect renal toxicity, i.e. decrease in glomerular filtration. Both dolutegravir and elvitegravir (within the fixed dose combination of TDF/FTC/elvitegravir/cobicistat) should be available in clinical practice soon, which will offer more options for the strategic use of integrase inhibitors to treat both HIV-1 and possibly HIV-2 infections.