HIV PGx - Stev

ART (antiretroviral therapy) is highly effective that HIV has evolved into a chronic disease. However ART is complicated by:

• Development of resistance to ART

• Complex drug distribution, transport and metabolism

• Drug associated toxicities

• All of the above

The Role of PGx has expanded greatly over past 10-20 years, but not yet commonly used for:

–CYP450 enzymes

–UGT (5-diphospho-glucuronosyltransferase)

What are some example where PGx are use in HIV?

• HIV resistance testing started in the early 2000’s

• HLA testing to predict hypersensitivity reaction to abacavir

• Tropism testing before using maraviroc

• All of the above

PGx for virus characteristics consist of:

–Resistance testing

–Coreceptor tropism

• True

• False

•PGx for host (patient) characteristics in HIV Tx are:

• UGT (5´-diphosph-glucuronosyltransferase)

• CYP2B6

• HLA-B*5701

• All of the above

Drug Resistance mutations occur frequently and spontaneously due to lack of 3´ to 5´ proofreading mechanism during viral replication

• True

• False

Drug Resistance mutations occur by amino acid substitutions, deletions and additions to the HIV genes for:

• Protease

• Envelope genes

• Integrase

• Reverse transcriptase

• All of the above

In Drug Resistance Testing, the HIV with no mutations is referred to wild-type virus, what are other considerations to keep in mind about ART,HIV and Resistance?

• Resistance mutations slows the speed at which the mutated virus can replicate

• If resistance exists and the ART is removed, wild-type virus will become predominant again

• The resistant HIV is archived

  –And will become predominant again if ART is restarted with the drug that the HIV is resistant to

• All of the above

HIV resistance testing has been recommended since 2000 and Current DHHS guidelines recommend testing at:

• Before starting ART if not started soon after diagnosis

• Resistance suspected due to increasing HIV RNA viral load for patients on ART or if viral load does decrease as expected

• Initial diagnosis:

  • May have been infected with resistant virus

  • 6-16% of patients may have transmitted resistance to at least one medication

• All of the above

which of the following are characteristics of current Genotype testing for Drug Resistance?

• Preferred method according to guidelines

• All sequence the protease and transcriptase genes

• Tests for integrase and envelope genes also available and must be requested separately

• Guidelines recommend consulting with an expert for interpretation

• All of the above

•Phenotypic testing in drug resitance testing:

–Inserts the HIV virus genes into a pseudovirus

–Pseudovirus replicated invitro with various concentrations of drugs to find IC50

–More expensive and takes longer for results (2-3 weeks)

–When compared to genotypic testing, results are comparable

–Can be useful when patient has multi-drug resistant virus

• True

• False