HIV and Gay Men by Rusi Jaspal & Jake Bayley

Author:Rusi Jaspal & Jake Bayley
Language: eng
Format: epub
ISBN: 9789811572265
Publisher: Springer Singapore

Integrase Strand Transfer Inhibitors

INSTIs (or integrases) were developed later than other classes of ARVs, with the first, raltegravir, being approved in 2007. It was given accelerated approval from the FDA due to its high effectiveness, especially in treatment-experienced patients who were resistant to other drugs. The enzyme, integrase, splices HIV DNA into the host cell’s genome. Once this enzyme is inhibited, further replication of HIV is stopped.

Clinically, integrases have been an extremely useful addition to the HIV treatment armamentarium. Those who developed resistance to other classes of drugs exhibited a good response to this class of drugs providing a lifeline of effective treatment for those who would otherwise have struggled to remain virologically suppressed. Also, the rate of viral decline in those taking INSTIs is much quicker when compared to other agents (Messiaen et al., 2013; Rockstroh et al., 2013). It is therefore extremely effective for treating patients with very high viral loads, such as those who are seronconverting to reduce onward transmission.

INSTIs remain a popular choice for many patients due to a relatively clean side effect profile with only a minority of patients experiencing sleep disturbance and insomnia. They have few interactions with other medicines allowing effective viral suppression for those with other health conditions who may be taking a pharmacopeia of other medicines. In clinical practice, they have also proven to be very useful for those engaging in chemsex given the few interactions with recreational drugs with less inadvertent overdose—a lethal phenomenon seen in those taking enzyme inhibitors such as ritonavir.

The newer INSTI, dolutegravir, has proven very popular due to a high genetic barrier to resistance and excellent tolerability for patients. Two recent studies, TANGO (van Wyk et al., 2020) and GEMINI (Cahn et al., 2019), have both shown that dolutegravir plus either lamivudine (a NRTI) or rilpivarine (a NNRTI) as dual therapy is just as effective as taking the standard three-drug regimen, with few side effects and almost no viral resistance. This is an important step in challenging the dogma of three-drug regimens allows less drug exposure to NRTIs, the usual backbone for ART, and also significant cost savings (3TC is amongst the cheapest of ARVs due to it being off patent for a number of years). Dual therapy may be the future of modern ART as newer medicines have improved genetic barriers to resistance with favourable pharmacokinetic profiles.

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