INSTIs

INSTIs, or integrase strand transfer inhibitors, are a class of antiretroviral drugs for HIV-1 infection. They block the HIV integrase enzyme, preventing the insertion of viral DNA into the host genome. By inhibiting the strand transfer step, INSTIs disrupt the replication cycle and, when used in combination with other antiretrovirals, help achieve viral suppression.

Commonly used INSTIs include raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. In many regimens, an INSTI is paired with two NRTIs such as tenofovir disoproxil/emtricitabine. Dolutegravir and bictegravir are often preferred first-line options because of potency and relatively high barriers to resistance. Cabotegravir is available as a long-acting injectable for select treatment regimens and for pre-exposure prophylaxis in some settings.

Administration and resistance: INSTIs are generally well tolerated and effective in achieving durable viral suppression. Resistance can develop with insufficient adherence and may involve mutations in the integrase gene; cross-resistance varies among agents. Dolutegravir and bictegravir typically retain activity against many resistant strains, contributing to their favorable resistance profiles.

Safety and interactions: INSTIs are typically associated with mild adverse events such as headache or insomnia. They have few major drug interactions, but absorption of certain agents can be reduced by divalent cations (calcium, magnesium) or iron; dosing should be spaced around supplements. Some INSTIs require dose adjustments when combined with strong enzyme inducers like rifampin.

Overview: INSTIs are widely used in contemporary HIV therapy due to potency, tolerability, and convenience. Guidelines commonly recommend regimens including an INSTI as first-line therapy, often with NRTIs, and ongoing development of long-acting formulations expands options for adherence.