How HIV Booster Drugs Work

There are drugs used in the treatment of HIV that can increase the plasma concentration of certain antiretroviral agents (ARVs) when used in combination therapy. Popularly known as "boosters," the drugs allow doctors to reduce the dosage and frequency of the attendant ARV while lowering the potential for drug-related side effects.

HIV boosters, also known as pharmacokinetic enhancers, should not be confused with vitamins or supplements marketed as "immune boosters," which have no known properties for either preventing or fighting HIV infection.

When HIV protease inhibitors (PIs) were first discovered in the mid-1990s, one the main challenges to researchers was the rapid speed in which the drugs were metabolized in the liver and cleared from the bloodstream. As a result, PIs required twice- to thrice-daily dosing. Not only did the high dosages increase the risk of drug toxicities, the high pill burden made adherence all the more difficult (and the development of resistance all the more likely).

In 1996, the drug Norvir (ritonavir) was approved for use in HIV by the U.S. Food and Drug Administration (FDA). While the drug was known to have antiviral properties, it was soon discovered that, even at very low doses, it could inhibit the very enzyme (CYP3A4) needed to metabolize PIs.

The discovery immediately impacted the way in which PIs were prescribed. Today, Norvir is rarely used for its antiviral action, but rather to increase the efficacy of the attendant PIs, while reducing the adverse effects associated with therapy.

The drug is also a component of the fixed dose combination PI, Kaletra (lopinavir + ritonavir).

(Please note - Norvir can interfere with plasma concentrations of other drugs you may be taking, sometimes resulting in serious to severe interactions. Please advise your doctor about any concomitant medications you are using when either Norvir or Kaletra is prescribed.)

In recent years, there has been much focus placed the development of other HIV boosters. It is envisioned that similar agents might not only further extend the efficacy of PIs, but do the same for other classes of ARVs—potentially affording unified, once-daily doses, while allowing greater "forgiveness" should doses be missed or a gap in therapy occur.

In 2012, a full 16 years after the introduction of Norvir, a second booster drug was finally approved by the FDA. Tybost (cobicistat), a component of the fixed-dose combination drug Stribild (elvitegravir + cobicistat + tenofovir + emtricitabine), is shown to inhibit both the CYP3A4 enzyme and certain intestinal proteins known to interfere with drug absorption.

While it has no antiviral properties of its own, Tybost is able to increase the efficacy of elvitegravir, an HIV integrase inhibitor, while achieving similar results with the PIs Reyataz (atazanavir) and Prezista (darunavir) and the nucleotide analogue Viread (tenofovir).

In early 2015, the FDA approved two, fixed dose combination drugs incorporating Tybost, including Evotaz (atazanvir + cobicistat) and Prezcobix (darunavir + cobicistat).

Other experimental boosters are under investigation, including a novel CYP3A4 inhibitor being developed by Sequoia Pharmaceuticals.