LAUSR

Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, the development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. We performed meta-analyses of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients. Odds ratios (ORs) of efficacy outcome data favoring INSTI use in different clinical settings demonstrated that compared with drugs of other classes, INSTIs have higher efficacy. For combination antiretroviral treatment (cART)-naïve patients and viral suppressed patients that switched to INSTI-based therapy, the ORs were 1.484 (95% CI, 1.229-1.790) and 1.341 (95% CI, 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virologic failure than to non-INSTIs (OR = 0.081, 95% CI, 0.004-1.849), whereas the opposite was observed for raltegravir (RAL; OR = 3.137, 95% CI, 1.827-5.385) and elvitegravir (EVG; OR = 1.886, 95% CI, 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir (BIC) was rare, while EVG and RAL had low genetic barriers to resistance and that the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring emergence of resistance to INSTIs and development of drugs with high genetic barriers are clear paths for future research.