Question

Sauron is an HIV-positive patient who also suffers from herpes and rheumatoid arthritis. He was diagnosed with HIV in the late 90s and was prescribed a combination of three antiretroviral (ARV) drugs comprising two nucleotide reverse-transcriptase inhibitors (NRTI) and one non-nucleotide reverse-transcriptase inhibitor (NNRTI). Quite recently, his ARV treatment was changed to a fixed-dose combination (FDC) of the same drugs. His doctor also prescribed fluconazole as prophylaxis for candida suppression.

a. If Sauron is taking interferon-α to treat the herpes, explain i) how it will exert a therapeutic effect and ii) how the frequency of its dosage can be reduced. (1½)

b. Describe how fluconazole would prevent growth of fungi such as Candida albicans. (2½)

c. Explain why it would be inadvisable for him to take cyclosporine for the treatment of rheumatoid arthritis while taking fluconazole. (1)

d. Describe how NRTIs would exert a therapeutic effect as a component of ARV treatment and provide two advantages of prescribing the ARVs as an FDC. (3½)

e. If Sauron had to be prescribed lopinavir due to resistance to the NNRTI in the FDC, what can he do to increase the bioavailability of lopinavir? (½)

f. Sauron was non-compliant to his antifungal prophylaxis and as such, he developed oral thrush which progressed to systemic candidiasis. He was hospitalised and administered a slow intravenous infusion of amphotericin B. After an hour of infusion, he started experiencing fever, chills, headache, muscle pain and nausea. What could be the cause of Sauron’s symptoms and how could this have been prevented? (1)

g. After recovery, Sauron develops influenza and uses oseltamivir for treatment. He notices that the antiviral is ineffective, which shocks him since he has used it the previous year with no problem. What could have caused this drug ineffectiveness?

Answer 1

a) interferon alfaaz is a non specific antiviral drug. It binds to cell surface receptor and affect viral replication. It generally given trice weekly the dose should be gradually reduced

b) fluconazole inhibit fungal cytochrome p450 enzyme and thus impair ergosterol synthesis leading to membrane abnormalities in the fungi

c) fluconazole increases plasma concentration of cyclosporine which lead to adverse effect and increased activity cyclosporine

d) NRTI inhibit nucleside reverse transcriptase enzyme and prevent the infection of new cell by virus Convenience and better pt compliance combined formulations ensure that a single drug will not be administrated

e) lopinavir should be combined with ritonavir to increase bioavailability

f) reactions occurs due to toxicity of amphotericin B. Intensity of reactions can be decreased with continued medication and inj of hydrocortisone 0.6mg/kg with infusion

g) due to development of resistance by mutation of viral neuraminidase enzyme