Human Immunodeficiency Virus (HIV, AIDS) (cont.)

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What are fusion inhibitors?

A fusion inhibitor blocks an early step in the viral life cycle. Enfuvirtide (Fuzeon, T-20) attaches to the envelope surrounding the virus and prevents it from entering the CD4 cells. This prevents the infection of CD4 cells by HIV. T-20 is the first approved drug in this class. It is given as a twice-daily subcutaneous injection (90 mg). It is used primarily in individuals who have developed resistance to other classes of drugs in order to create a new potent combination. Like all other antivirals, it is most useful in those taking other active drugs at the same time in order to optimize the chance of getting viral loads to undetectable levels and to prevent the development of drug resistance.

What is a CCR5 antagonist?

The first available drug in this class is called maraviroc (Selzentry, MVC), which is now approved for use in combination therapy in treatment-experienced and naïve patients who do not have detectable CXCR4-using virus as determined by a tropism assay. This is a unique drug in a new class that blocks viral entry by interacting with the CCR5 molecule on the surface of the CD4 cell. It is known that HIV first binds to the CD4 molecule on the surface of CD4 cells and then connects with the CCR5 or CXCR4 molecule. Only after this second step is the virus able to enter the cell. The CCR5 antagonist prevents viruses that use CCR5 from getting into the cell. What is unique about this drug compared to others is that 20%-50% of patients have viruses that are able to use the CXCR4 receptor. In these cases, CCR5 antagonists do not appear to be active at suppressing virus. Therefore, in order to know if the drug will work for a given patient, a new test needs to be performed, the so-called tropism assays. This test will tell the provider and patient whether there is virus that uses CXCR4, in which case the patient would not be a candidate for MVC, or if they only have viruses that use CCR5, in which case MVC should be an active drug. Without tropism results, it is impossible to know whether MVC will be an active drug for a given patient.

MVC is typically dosed at either 300 mg or 150 mg twice daily, depending upon what other drugs it is given with. If the patient is taking any RTV, then they would usually receive the 150 mg dose. If RTV is not being used as part of the regimen, they would generally receive the 300 mg dose and sometimes even higher if it is being used with drugs like ETR. HIV providers are aware that whenever using any anti-HIV medications attention must be given to possible drug interactions.

What is an integrase strand transfer inhibitor?

The first available drug in this class is RAL which is very potent at suppressing HIV in all patients who have never been on this drug or others in the class. It was initially approved for treatment-experienced patients with drug-resistant virus. It is also now approved for those starting therapy for the first time. The approved dose of RAL is 400 mg twice daily. As noted above, a second drug in this class, EVG was recently approved for use as first-line therapy as part of the fixed-dose combination pill of TDF/FTC/COBI/EVG. This drug is well tolerated and given as one pill per day, but unlike RAL it does need to be taken with food and it has interactions with other drugs, so it must be used with caution in those on multiple medications and there is an effect on measures of kidney function so it should not be used in individuals with moderate to severe underlying kidney disease. EVG is also being considered as a stand-alone medication that can be given outside of the fixed-dose combination pill, including for those with drug-resistant virus who want to create a new regimen with an InSTI other than RAL. The most recently approved antiretroviral is the InSTI DTG that is currently recommended for those starting therapy for the first time with either TDF/FTC or ABC/3TC and will soon be available as a fixed-dose combination of ABC/3TC/DTG that can be given as a single pill per day. This drug has a limited number of drug-drug interactions and is generally well tolerated. Like COBI, it too results in a small effect on the measure of kidney function, which does not reflect actual kidney damage but does require careful monitoring.

Usual dosing schedule and meal restrictions for InSTIs
  RAL EVG1 DTG
Dose in each pill (mg) 200 150 502
Schedule 1 twice a day 1 per day 1 per day
Meal restrictions None With food None
RAL, raltegravir; EVG, elvitegravir; DTG, dolutegravir. 1Currently, it is only approved as part of the fixed-dose combination pill of EVG (150 mg)/COBI (150 mg)/FTC (200 mg)/TDF (300 mg). Currently, it is being reviewed as a single pill that can be given along with pharmacologic boosting agents, such as COBI or RTV in other HIV-infected patient populations. 2DTG must be given twice per day in patients with history of InSTI resistance.
Medically Reviewed by a Doctor on 8/5/2014

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