1.
A 71-year-old woman was admitted to the hospital with a 2-day history of progressive
dyspnea, fever, cough and wheezing. Chest radiograph was normal but a bronchoscopy
showed marked erythema of the trachea and bronchi, with multiple ulcerations. A
bronchial biopsy confirmed the diagnosis of herpetic tracheobronchitis. The patient
received IV acyclovir for 3 days but no improvement was seen. Resistance to acyclovir
was suspected and an alternative drug was given IV. Which of the following drugs was
most likely administered?
Correct Answer
A. Foscarnet
Explanation
Learning objective: outline the therapeutic uses of foscarnet.
Answer: A
Herpetic tracheobronchitis has been documented in both immunocompromised and
immunocompetent individuals. Normal hosts typically are elderly individuals. Early detection of
herpetic tracheobronchitis appears critical so that acyclovir, which is a drug of first choice for
HSV infections, can be given during the time of peak viral replication, which tends to coincide
with symptomatic clinical illness. The most common cause of failure of acyclovir therapy is the
presence of thymidine kinase deficient strains of HSV. Since acyclovir must be phosphorylated
by a viral thymidine-kinase to become a nucleotide analog which inhibits viral DNA-polymerase,
these strains are acyclovir-resistant. In this case foscarnet, which directly inhibits viral DNApolymerase,
represents an useful alternative.
B, C, D) Saquinavir, amantadine and zidovudine are not active against HSV.
E) Trifluridine is effective against HSV but is very toxic and therefore is used only topically.
2.
A 35-year-old man visited an ophthalmologist because of a foreign body sensation,
lacrimation, photophobia and blurred vision in his left eye. Eye examination showed a
conjunctival hyperemia and a branched lesion of corneal epithelium with terminal bulbs,
swollen border and a central ulcer. A presumptive diagnosis was made and a topical
therapy with eye drops was ordered. Which of the following drugs was most likely
prescribed?
Correct Answer
E. Trifluridine
Explanation
Learning objective: outline the therapeutic uses of trifluridine.
Answer: E
The symptoms and signs of the patient suggest that he was most likely affected by herpes
simplex keratitis, a common ocular disorder and one of the most frequent causes of blindness in
the U.S. The illness is usually treated topically and trifluridine eye drops 8-9 times/daily are
effective in most case. Occasionally oral acyclovir is indicated, especially for recurrent infection.
A) This is a drug for viral hepatitis
B, C, D) These are drugs for HIV infection
F) This is a drug for influenza
3.
A 56-year-old man suffering from viral hepatitis B had started a treatment with
interferon alpha-2a, but nine month later he was still HBeAg positive. The
gastroenterologist decided to stop interferon and start another drug. Which of the
following drugs was most likely prescribed?
Correct Answer
F. Lamivudine
Explanation
Learning objective: outline the use of Interferon alpha-2a in viral hepatitis B.
Answer: F
Lamivudine has been the first nucleoside analog approved by FDA for use in patient with viral
hepatitis B. It inhibits HBV DNA polymerase and HIV reverse transcriptase by competing with
deoxycytidine triphosphate for incorporation into the viral DNA. Lamivudine is an effective agent
for patients with chronic hepatitis B. It can suppress HBV DNA to undetectable level in about
40% of patient and can normalize ALT in up to 75% of patients. Unfortunately resistance is a
problem since it can be 70% at five years of therapy.
A, B, C, D, E) these antiviral drugs are not effective against hepatitis B.
4.
A 41-year-old woman with AIDS started a highly active antiretroviral therapy with
lamivudine, abacavir and efavirenz. Which of the following adverse effects could most
likely occur during the therapy?
Correct Answer
A. Erythematous skin rash
Explanation
Learning objective: describe the most likely adverse effect of the concurrent administration
of abacavir and efavirenz.
Answer: A
Abacavir and efavirenz can frequently cause skin rashes. Abacavir can cause allergic reactions
in about 8% of patients, and erythematous skin rash occurs in about one half of patients
presenting such reactions. Efavirenz can cause skin rashes in up to 28% of patients. Since the
present patient was taking both drugs an erythematous skin rash could most likely occur.
B) Efavirenz can cause psychotic symptoms, but the frequency of such adverse effects is
exceedingly low.
C, D, E) The risk of these adverse effects is negligible.
5.
A 31-year-old HIV positive man was found to have a CD4 lymphocyte count of 122
cell/mm at the last control visit. A 3 HAART (Highly Active Antiretroviral Therapy) was
started which included a drug that does not require phosphorylation to be active. Which
of the following is an antiretroviral drug with this property?
Correct Answer
A. Efavirenz
Explanation
Learning objective: identify the antiretroviral drugs that do not need phosphorylation to
became active.
Answer: A
The HAART therapy can be non nucleoside based (i.e. one NNRTI+ two NRTIs). Efavirenz is a
NNRTI. Unlikely NRTI, all NNRTI do not require phosphorylation to became active.
B) Foscarnet does not require phosphorylation to be active but it is not an antiretroviral drug.
C, D, E, F) These drugs are NRTIs, and therefore they required phosphorylation to become
active.
6.
A 34-year-old pregnant woman at term was admitted to the hospital for delivery. The
woman had a long history of AIDS and was following a HAART therapy (ritonavir +
lamivudine + tenofovir). An oral dose of nevirapine was given to the woman at the onset
of labor. Which of the following statements best explains the reason for this
administration?
Correct Answer
D. To prevent HIV transmission in the newborn
Explanation
Learning objective: outline the antiretroviral therapy to prevent mother-to-infant HIV
transmission during pregnancy
Answer: D
It has been shown that a single dose of nevirapine is effective in the prevention of transmission
of HIV from mother to the newborn ,when administered to women at the onset of labor and
followed by a oral dose to the neonate within 3 days after the delivery. Nevirapine is therefore
more convenient than zidovudine, which must be administered for much longer time to the
mother and the newborn, to obtain protection from HIV transmission.
7.
A 61-year-old woman suffering from viral hepatitis B was admitted to the hospital for a
follow up examination. She was found to have >105 HBV DNA copies/mL and ALT of 210
U/L (normal <20). A therapy with entecavir was prescribed. The inhibition of which of the
following viral enzymes most likely mediated the therapeutic effect of the drug in the
patient’s disease?
Correct Answer
A. DNA-polymerase
Explanation
Learning objective: explain the mechanism of action of entecavir.
Answer: A
Entecavir is a guanosine derivative that inhibits HBV DNA polymerase. The drug is more potent
than lamivudine and is highly effective in lamivudine resistant strain. Clinical resistant to
entecavir is very rare (< 1% at 4 years).
B, C, D, E, F) These enzymes are not inhibited by entecavir
8.
A 23-year-old woman with AIDS came to the hospital complaining of floating spots in
her vision and difficulty in reading. Funduscopic examination revealed the presence of
alternating areas of hemorrhagic tissue and fluffy, white patches in the proximity of
retinas of both eyes consistent with hemorrhagic retinitis. Which of the following drugs
was most likely prescribed for the treatment of the patient’s ocular disorder?
Correct Answer
C. Ganciclovir
Explanation
Learning objective: outline the therapeutic uses of gancyclovir.
Answer: C
A hemorrhagic retinitis in an AIDS patient strongly suggests the diagnosis of cytomegalovirus
retinitis, which accounts for more than 75% of cytomegalovirus end-organ disease in HIV
positive patients. Treatment options for cytomegalovirus retinitis include ganciclovir, foscarnet,
and cidofovir. These drugs are administered IV or by intraocular injections. Fomivirsen is
another drug used for cytomegalovirus retinitis and administered only by intraocular injection.
A, B, D) These antiviral drugs are not used for cytomegalovirus retinitis.
E, F) These drugs are not antiviral agents.
9.
A 34-year-old man presented to the hospital with jaundice and complaints of
incapacitating fatigue and vague intermittent abdominal pain for the past month. The
patient had a history of IV drug abuse and of alcohol abuse. Hepatitis serologic tests
were positive for HBsAg. Which of the following drugs would be appropriate for this
patient?
Correct Answer
D. Interferon alpHa-2a
Explanation
Learning objective: outline the use of interferon alpha-2a in viral hepatitis B.
Answer: D
The chronic occurrence of jaundice in a young patient is suggestive of hepatitis and the
presence of hepatitis B surface antigen (HBsAG) in serum is diagnostic for HBV infection.
Approximately 5% of the world’s population is infected with HBV. The most prominent risk
factors associated with the disease include sexual contacts (> 50%) and injection drug use
(15%). Subclinical infections are common, but 25% of carriers develop chronic active hepatitis.
Worldwide one million deaths a year are attributed to HBV-related diseases, including
hepatocellular carcinoma. Drugs for the treatment of chronic hepatitis B include interferons,
adefovir, entecavir, tenofovir and lamivudine. These drugs are only moderately effective in
treating the disease since remission may be sustained but in many patients viral replication
reappears following cessation of therapy. Interferons are cytokines that posses antiviral,
immunomodulating and antiproliferative actions. They induce over two dozen proteins in the
host’s cells, which contribute to viral resistance through different mechanisms including:
1) inhibition of viral penetration and uncoating
2) inhibition of synthesis of viral DNA and RNA
3) inhibition of viral assembly and release
A, B, C, E, F) These antiviral drugs are not effective against hepatitis B.
10.
A 35-year-old man with AIDS presented to the clinic for a follow up visit. He was
concerned because he noticed a growth on his neck. He has been following a Highly
Active Antiretroviral Therapy (HAART) for 4 months. Physical examination disclosed an
accumulation of fat on his upper back. Pertinent lab results were: total cholesterol 380
mg/dL, triglycerides 420 mg/dL, blood glucose 240 mg/dL. All lab values were within
normal limits before starting the HAART. Which of the following pairs of drugs most likely
caused the signs and the lab values of this patient?
Correct Answer
E. Ritonavir and saquinavir
Explanation
Learning objective: describe the main adverse effects of protease inhibitors.
Answer: E
Sometimes the HAART in AIDS is carried out with 4 different drugs, namely two nucleoside
reverse transcriptase inhibitors and two protease inhibitors. The use of protease inhibitors has
led to disorders in carbohydrate and lipid metabolism. The precise cause of this abnormality is
not known but it is suggested that protease inhibitors can inhibit also human proteases that
regulate lipid and carbohydrate metabolism. The protease inhibitor induced syndrome includes
altered body fat distribution, hyperlipidemia and hyperglycemia. The syndrome can occur in up
to 50% of patients treated with protease inhibitors for one year, but in some cases it appears as
early as two weeks after the beginning of therapy.
The present patient most likely received a 4 drug antiretroviral regimen including two protease
inhibitors (ritonavir and saquinavir), which can account for his metabolic disturbances.
A, B) These drugs are not antiretroviral agents.
C, D) These drugs are nucleoside analogs extensively used in HAART, but they do not cause
the metabolic disturbances mentioned above.
11.
A 35-year-old man with AIDS started a therapy which included a lopinavir/ritonavir
combination. Which of the following statements best explains the main reason of this
combination regimen?
Correct Answer
E. Ritonavir inhibits lopinavir metabolism
Explanation
Learning objective: explain the reason of ritonavir/lopinavir combination.
Answer: E
Ritonavir is an inhibitor of the CYP3A4 enzymes. Even when given in subtherapeutic doses the
drug inhibits the metabolism of lopinavir with a resultant increase of lopinavir plasma levels
which may exceed the EC90 for most strains of HIV. In this combination therefore ritonavir is
mainly acting as a pharmacokinetic enhancer.
A, B, C, E, F) (see explanation above)
12.
A 38-year-old woman suffering from chronic hepatitis B started a treatment with a
drug that is able to inhibit several steps of hepatitis B virus replication including
uncoating, early transcription, translation, assembly and release. Which of the following
drugs was most likely administered?
Correct Answer
C. Interferon alpHa-2a
Explanation
Learning objective: explain the mechanisms of antiviral action of interferons.
Answer: C
Interferons are drugs that can inhibit several steps of HBV replication including uncoating, early
transcription, translation, assembly and release. The inhibition of translation of viral proteins
seems the main mechanism.
A, B, D, E) These drugs are effective in viral hepatitis B, but they cannot inhibit multiple steps of
the viral growth cycle.
13.
A 54-year-old man with AIDS was found to have a CD4 lymphocyte count of 110
cell/mm at the last control visit. The patient had an extensive hi 3 story of treatment with a
variety of drug regimens without sustained clinical benefit. He was currently taking
zalcitabine, lamivudine and efavirenz. The physician decided to add to another drug that
acts by blocking the insertion of reversed-transcribed HIV DNA into the chromosomes of
the host cells. Which of the following drugs was most likely prescribed?
Correct Answer
D. Raltegravir
Explanation
Learning objective: explain the mechanism of action of raltegravir
Answer: D
Raltegravir is the first integrase inhibitor approved by FDA, since it was shown that the drug,
plus optimized background therapy, provided better viral suppression than optimized
background therapy alone for at least 48 weeks. Raltegravir blocks the enzyme that inserts the
viral genome into the DNA of the host cell.
A) This drug is a nucleoside reverse transcriptase inhibitor,
B, C) These drugs are protease inhibitors.
E, F) These drugs are not antiretroviral agents.
14.
A 32-year-old woman visited her physician complaining of some very painful blisters
on her abdomen. Physical examination showed localized blisters on her left abdomen
consistent with a varicella-zoster infection. A drug therapy was started. Which of the
following enzymes was most likely inhibited by the administered drug?
Correct Answer
B. DNA-polymerase
Explanation
Learning objective: explain the mechanism of action of acyclovir.
Answer: B
Drugs for VZV infection include acyclovir, famciclovir and penciclovir. These drugs are
phosphorylated to the triphosphate derivatives which are potent inhibitors of both viral DNA and
mammalian DNA polymerase. However viral DNA polymerase is more sensitive to inhibition
than the DNA polymerase of the host cell.
A, C, D, E, F) These enzymes are not inhibited by acyclovir.
15.
A 72-year-old man was admitted to the hospital with one week history of fever, night
sweats and shortness of breath. Blood exams on admission were notable for hemoglobin
10 g/dL and creatinine 3.2 mg/dL. Physical examination showed decreased lung sounds
bilaterally. A viral culture from bronchoalveolar lavage was positive for HSV and a therapy
with IV acyclovir was started. The patient was at increased risk of developing which of the
following adverse effects as a result of this therapy?
Correct Answer
B. Renal failure
Explanation
Learning objective: describe the adverse effects of acyclovir.
Answer: B
More than 90% of acyclovir is eliminated as such by the kidney and nephrotoxic effects can
occur with parenteral administration. These effects are more likely in the present patient
because of its decreased renal function (see creatinine levels).
A, C, D, E, F) Acyclovir has no significant toxicity on bone marrow, liver and pancreas.
16.
A 5-month-old baby girl born prematurely at 31weeks’ gestation was found to have
bronchopulmonary dysplasia that needed oxygen use. Recently a respiratory syncytial
virus outbreak occurred in the community and the pediatrician decided to order a drug to
prevent the RSV infection. Which of the following drugs was most likely prescribed?
Correct Answer
E. Palivizumab
Explanation
Learning objective: outline the prophylactic uses of palivizumab.
Answer: E
Palivizumab is a humanized monoclonal antibody that bind to the A antigen site on the F
surface protein of RSV. It is licenced for the prevention of RSV infection in high risk infant and
children such those with pulmonary dysplasia, like in the present case.
A, B, C, D, F) These drugs are not active against RSV infection.
17.
A 31-year-old woman with a two year history of AIDS reported of watery, bloody
diarrhea for approximately two weeks with accompanying abdominal pain. A colon biopsy
revealed cytomegalovirus inclusions in the colonic mucosa. An IV therapy was started.
Which of the following viral enzymes was most likely inhibited by the administered drug?
Correct Answer
A. DNA-polymerase
Explanation
Learning objective: explain the mechanism of action of gancyclovir.
Answer: A
In immunocompromised patient cytomegalovirus infection is a major cause of morbidity and
mortality. The infection can cause an ulcerative disease of the colon, like in the present case.
Gancyclovir is a drug of choice for CMV infection and was most likely administered to the
patient. The drug is phosphorylated by a CMV phosphotransferase or by a HSV thymidine
kinase to the corresponding nucleotide which can inhibit DNA polymerase of CMV, HSV and
VZV, so blocking viral DNA synthesis.
B, C, D, E, F) These enzymes are not inhibited by gancyclovir.
18.
A 35-year-old HIV positive man presented to the hospital for a follow up visit. His CD4
lymphocyte count was found 350 cells/mm3. An HAART (Highly Active Antiretroviral
Therapy) was initiated. Which of the following triple drug regimen was most likely used?
Correct Answer
E. Zidovudine + didanosine + saquinavir
Explanation
Learning objective: outline the highly active antiretroviral therapy of AIDS.
Answer: E
HAARTs are prescribed to many HIV positive persons even before they develop symptoms of
AIDS. This therapies have dramatically altered the natural progression of infection and
significantly improved the quality of life of many HIV infected patients. An HAART usually
includes two NRTI (like zidovudine and didanosine) plus a protease inhibitor (like saquinavir) or
a NNRTI.
A, B, C, D) All these drug combinations include at least one drug that is not an antiretroviral
agent.
19.
A 44-year-old man was recently found HIV positive and started a highly active
antiretroviral therapy (HAART) with two nucleoside reverse transcriptase inhibitors (NRTI)
and one protease inhibitor (PI). Which of the following two steps in the HIV growth cycle
were specifically affected by this drug regimen?
Correct Answer
D. Transcription and assembly
Explanation
Learning objective: identify the steps of HIV growth cycle specifically affected by NRTI and
PI.
Answer: D
Nucleoside reverse transcriptase inhibitors block the reverse transcription of RNA into DNA.
Protease inhibitors block the proteolytic cleavage of immature budding particles, so preventing
the assembly of structural proteins around a genomic RNA to form a nucleocapsid.
A, B, C, E) At least one of these two steps is not affected by nucleoside reverse transcriptase
inhibitors or protease inhibitors.
20.
A 34-year-old man recently diagnosed with AIDS was found to have a viral load of
185000/copies mL during a control visit. The patient had been following a highly active
antiretroviral therapy with efavirenz, stavudine, lopinavir saquinavir and raltegravir for five
months. A lab test indicated a mutation in the gene encoding the reverse transcriptase
enzyme. Which of the following pairs of antiretroviral drugs most likely became
ineffective because of the development of resistance?
Correct Answer
D. Efavirenz and stavudine
Explanation
Learning objective: explain the main reasons of resistance to antiretroviral therapy.
Answer: D
Since resistance was due to a mutation in the gene encoding the enzyme reverse transcriptase,
drugs that are reverse transcriptase inhibitors were no longer effective, and this was most likely
the reason of the failure of the ongoing therapy (see the high viral load).
A, B, C, E, F) In all these combinations one or two drugs were most likely still effective since
their mechanism of action does not involve the enzyme reverse transcriptase.