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Nursing Pharmacology: Antiviral Drugs
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Antiviral Drugs
Anti-viral drugs with activity against HIV (Human Immunodeficiency Virus)
HIV-1 Pathophysiology/Pathogenesis: HIV Disease Presentations
Drug-Induced Myocardial Disease
Some concerns about possible relationships between combination highly active antiretroviral treatment (cART a.k.a. HAART) and heart disease were evaluated by the "Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D)" study which began in 1999.5
This group considered over 23,000 patients from 11 previously defined cohorts initially from December 1999 to April 2001.7
The
incidence of myocardial infarction was shown to increase with duration
of combination anti-retroviral treatment.7
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The study group concluded that cART was an independent risk factor accounting for about a 25% relative increase in the rate of myocardial infarction/year of exposure during the first 4-6 years of cART therapy.
In 2003 cumulative exposure to protease inhibitors (PIs) was found to also increase myocardial infarction rate in HIV patients to an extent not fully accounted for by protease inhibitor-associated dyslipidemia.5
The basis
for clinical effectiveness of HIV protease inhibitors is that HIV
protease is required for viral growth.6
HIV protease catalyzes conversion of viral core proteins of the structural proteins.6
Human aspartyl proteases, such as renin, pepsin, gastricsin, and cathepsins D and E), consist of only one polypeptide chain and are not appreciably inhibited by HIV protease inhibitors.
Human aspartyl proteases exhibit poor affinity for HIV protease inhibitors and this characteristic is the basis for viral vs. human aspartyl protease pharmacological selectivity.1
A number of studies have been published that investigated possible association between specific antiretroviral drugs and myocardial infarction risk in HIV-infected patients.5,10
A recent study examined the relationship between abacavir (Ziagen) administration and myocardial infarction risk.10
The risk of exposure to other nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and non-NRTIs was also evaluated.
Short-term/recent abacavir (Ziagen) administration was associated with an increased likelihood of myocardial infarction but only in the subset of individuals using cocaine or intravenous drugs.10
An increased
risk of myocardial infarction was noted following cumulative exposure to
all protease inhibitors except saquinavir (Invirase).
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