Boosted PI + 2 or 3 NRTIs Non-inferiority [40] Second-Line RAL + LPV/r vs. LPV/r + 2 or 3 NRTIs Non-inferiority [41] FLAMINGO DTG + TDF/FTC or ABC/3TC vs. DRV/r + TDF/FTC or ABC/3TC Superiority [47] RAL raltegravir, TDF tenofovir disoproxil fumarate, FTC emtricitabine, EFV efavirenz, EVG/c cobicistat-boosted elvitegravir, ATV/r ritonavir-boosted atazanavir, ABC abacavir, 3TC lamivudine, DTG dolutegravir, PI protease inhibitor, LPV/r

ritonavir-boosted selleck products lopinavir Importantly, INSTIs can be used for second-line treatment against HIV strains that are resistant against other drug classes, including NRTI, NNRTI, and PI [55–62] (Table 1). In particular, RAL was shown to be efficacious for patients who displayed resistance to three classes of drugs other than INSTIs [58]. In addition, RAL combined with a ritonavir-boosted PI was non-superior to ritonavir-boosted PIs plus two or three NRTIs in patients who had previously failed NNRTI-based treatments [40]. RAL was also non-inferior to LPV/r as a second-line drug for patients who had failed selleck chemicals regimens consisting of a NNRTI and two PF477736 price NRTIs [41]. Treatment-experienced patients can also benefit from the use of INSTIs for reasons of toxicity, convenience, or absence of drug interactions [41, 63, 64]. Although switching

from LPV/r/TDF/FTC to RAL/DRV/r in individuals with suppressed viral load resulted in sustained viral suppression, it did not improve renal function at week 48 [42]. In contrast, RAL has a positive impact on bone mineral density compared to standard second-line treatments [5]. Whether treatment

intensification with INSTIs might benefit individuals with suppressed viral loads is beyond the scope of this review [65–69]. Studies have compared the efficacy of the different INSTIs in suppressing HIV viral load. In the 145 Study, EVG demonstrated non-inferiority to RAL at weeks 48 and 96 in highly treatment-experienced patients [43, 44]. DTG was non-inferior to RAL in attainment of viral 3-mercaptopyruvate sulfurtransferase suppression in treatment-naïve individuals at week 48 [45]. In contrast, DTG performed better than RAL in highly treatment-experienced INSTI-naïve individuals who were enrolled in a study termed SAILING (A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults) [46]. Overall INSTI-based regimens have shown low toxicity and an absence of unfavorable drug–drug interactions. The yearly costs of the various INSTI-containing regimens are comparable among the three drugs, i.e., approximately 30,000 USD/year [70]. Sequential Strategy for the Use of Integrase Inhibitors and the Issue of Resistance The concept of sequential strategy in regard to integrase inhibitors has not been fully explored. Although little information is available on this subject, the following facts are well-known.