HIV Drugs

jmanderson's version from 2016-02-11 00:26

PowerPoint Objectives


Question Answer
goals of anti-HIV treatment1) Achieve durable virologic suppression (monitor viral load and CD4 count); 2) Stabilize or restore immune function (ART often leads to ↑ in the CD4 cell counts of >50-150 cells/mm3/year; 3)Maintain or improve the patient’s quality of life; 4) Reduce HIV related mortality and morbidity
the key viral enzyme that converts viral RNA to DNA.reverse transcriptase
the two categories of ART used initially against HIV-1 infections1 Protease inhibitor + 2 NRTIs or 4 regimens with Integrase Inhibitor (II) + 2 NRTIs (INSTI)
Give the two NRTIs that are used in almost all initial ARTs.Emtricitabine (FTC) and Tenofovir (TDF)
Analyze how Nucleoside reverse transcriptase inhibitors (NRTIs) reduce viral multiplication.the early essential step of HIV replication (reverse transcriptase) by incorporating false nucleic acids into newly produced proviral DNA. The nucleic acids lack 3’-OH group, thus incorporation into DNA terminates chain elongation.
NRTIs MOAnucleoside and nucleotide analogues which inhibit reverse transcription. HIV is an RNA virus and hence unable to become integrated into the DNA in the nucleus of the human cell; it must be "reverse" transcribed into DNA.
NNRTIs MOAinhibit reverse transcriptase by binding to an allosteric site of the enzyme; NNRTIs act as non-competitive inhibitors of reverse transcriptase. NNRTIs affect the handling of substrate (nucleotides) by reverse transcriptase by binding near the active site.
Proteasecleaves viral polyprotein into active viral enzymes (reverse transcriptase, protease, and integrase)
Protease Inhibitors MOAbind reversibly to active site of HIV protease → viral particles become immature and noninfectious → inhibits viral replication in any infected cell
Give the three drugs in the one PI-based ART regimen recommended for naïve HIV patients.Protease Inhibitor + 2 NRTIs [Darunavir/ritonavir & tenofovir (TDF) + emtricitabine (FTC)]
Integrase inhibitors examplesdolutegravir (DTG), elvitagravir (EVG), raltegravir (RAL)
integrase inhibitors MOAInhibits that viral enzyme integrase that “integrates viral and host cell DNA”
Describe the role of ritonavir in an ART.Concomitant use of low-dose ritonavir and certain other HIV protease inhibitors results in increased plasma concentrations of the other Protease Inhibitor.
Enfuvirtide indicationadvanced HIV-1 infection pts; ongoing viral replication despite antiretroviral therapy (e.g., pt is not doing well on their current ART regimen)
CCR5 and CXR4 receptor rolechemokine receptors on T-cells that are used by HIV during viral entry (HIV R5 strain binds to CCR5 and X4 strain binds to CXR4).
Maraviroc MOACCR5 antagonist → binds at an allosteric site (alternative site) of the receptor → inhibits HIV viral entry

HandOut Objectives


Question Answer
two significant tests to be done to determine the severity of HIV infection1) Plasma HIV RNA levels (indicates the magnitude of HIV replication and its associated rate of CD4 T-cell destruction); 2) CD4 T-cell counts = indicated the extent of HIV-induced immune damage already suffered
Zidovudine AEbone marrow suppression
Stavudine AEperipheral neuropathy
Didanosine AEpancreatitis, peripheral neuropathy
Describe two indications that drug failure has occurred with anti-retroviral agents.1) Inadequate viral suppression; 2) Unsatisfactory increase in CD4 count
Describe a major adverse effect to anti-retrovirals (particularly NNRTIs and PIs), how it is monitored and defined.Hepatotoxicity - monitor liver enzymes (ALT/AST)
Apply the enzyme that metabolizes all PIs to a clinically-relevant case scenario.CYP3A4
the population that should not receive efavirenzPts who have previously demonstrated clinically significant HYPERSENSITIVITY (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions)
Explain the role of cobicistat in ARTs in which it is to inhibit liver enzymes that metabolize other medications used to treat HIV, notably elvitegravir, an HIV integrase inhibitor.
Noninferiority trialstest whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use.

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