HIV-1 integrase strand transfer inhibitors: A review of current drugs, recent advances and drug resistance.

Antiretroviral therapy (ART) has been imperative in controlling the HIV epidemic. Most low- and middle-income countries (LMICs) have used nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) extensively in the treatment of HIV. However, integrase strand transfer inhibitors (INSTIs) are becoming more common. Since their identification as a promising therapeutic drug, significant progress has been made which has led to the approval of five INSTIs by the Food and Drug Administration, i.e. Dolutegravir (DTG), Raltegravir (RAL), Elvitegravir (EVG), Bictegravir (BIC), and Cabotegravir (CAB). INSTIs have shown to effectively halt HIV-1 replication and are commended for having a higher genetic barrier to resistance, in comparison to NRTIs and NNRTIs. More interestingly, DTG has shown a higher genetic barrier to resistance compared to RAL and EVG, and CAB is being used as the first long-acting agent in HIV-1 treatment. Considering the increasing interest in INSTIs for HIV-1 treatment, we focus our review on the retroviral integrase, development of INSTIs and their mode of action. We also discuss each of the INSTI drugs, including potential drug resistance and known side effects.