The Rise of Integrase Inhibitors

Raltegravir (Isentress) was the first integrase inhibitor to be approved for the treatment of HIV infection. This drug helps to quickly suppress production of HIV and is generally well tolerated and has few significant interactions with other drugs. Raltegravir can be used by people who are new to anti-HIV therapy or by treatment-experienced people. One possible drawback of this drug is that it must be taken twice daily; a randomized clinical trial found that it was not as effective when taken once a day. An advantage of raltegravir is that it has been in use for several years and has a good track record of safety and efficacy.

Two integrase inhibitors under development for HIV treatment are as follows:

• dolutegravir (S/GSK 1349572)
• elvitegravir

Preliminary results suggest that both of these drugs are likely to be as powerful as raltegravir and, in general, also well tolerated. The newer integrase inhibitors may offer one advantage over raltegravir -- they can be taken once daily.

Elvitegravir

In the case of elvitegravir, once-daily dosing is made possible with the use of another anti-HIV drug that raises and maintains the concentration of elvitegravir in the blood. Drugs that are used to raise the concentrations of another drug are called PK boosters (pharmacokinetic boosters). An example of a PK booster commonly used today is ritonavir (Norvir). A small dose of ritonavir is taken to boost the concentration of commonly used HIV medicines such as these:

• atazanavir (Reyataz)
• darunavir (Prezista)
• lopinavir (in Kaletra)

Gilead Sciences, the developer of elvitegravir, is also testing a novel PK booster for use with elvitegravir called cobicistat (GS-9350). This will allow Gilead to put several more of its drugs into one pill, for example:

• elvitegravir + cobicistat + tenofovir + FTC

This particular combination has been nicknamed the quad by researchers.

Dolutegravir

Dolutegravir is being developed by ViiV Health Care together with GlaxoSmithKline. It is therefore likely to be co-formulated with other drugs made by these companies, such as Kivexa, a fixed-dose combination of the anti-HIV drugs 3TC + abacavir.

All drugs have side effects and as both dolutegravir and elvitegravir get tested in larger numbers of people, doctors will have a better idea of their safety and effectiveness.