THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

31. Human Immunodeficiency Virus and the Acquired Immune Deficiency Syndrome - Camille W. Thornton, PharmD

31-1. Overview

Introduction

Human immunodeficiency virus (HIV) is a retrovirus that depletes the helper T-lymphocytes (CD4 cells), resulting in continued destruction of the immune system and subsequent gradual development of opportunistic infections and malignancies.

Acquired immune deficiency syndrome (AIDS) is HIV with a CD4 count lower than 200 cells/mm3 or a history of opportunistic infection (e.g., unexplained fever for more than 2 weeks, thrush, Pneumocystis jiroveci pneumonia, toxoplasmosis, cryptococcal meningitis, histoplasmosis, Mycobacterium avium).

Epidemiology

At the end of 2007, global estimates of children and adults with HIV/AIDS were as follows:

• People living with HIV/AIDS: 33 million

• New HIV infections in 2007: 2.7 million

• Deaths attributable to HIV/AIDS in 2007: 2 million

• Cumulative number of deaths attributable to HIV/AIDS: 33 million

Complete current world epidemiology can be found at www.unaids.org.

At the end of 2006, estimates of children and adults with HIV/AIDS in the United States were as follows:

• People living with HIV/AIDS: 850,000-950,000

• New HIV infections in 2006: 56,300

• Deaths attributable to HIV/AIDS in 2006: 19,454

• Cumulative number of deaths attributable to HIV/AIDS: 549,594

• People who do not know they are infected with HIV: 180,000-280,000

Complete current U.S. epidemiology can be found at www.cdc.gov/hiv/topics/surveillance/resources/slides/epidemiology/index.htm.

HIV has two common subtypes:

• HIV-1: most commonly found in the United States

• HIV-2: most commonly found in Africa

Clinical Presentation

• Patient has an opportunistic infection.

• Patient is not ill but has tested positive for HIV.

• Patient has acute retroviral syndrome:

• 50% to 90% of patients acutely infected with HIV experience some of the symptoms.

• Symptoms generally appear 2-4 weeks after virus exposure.

• Duration of the clinical syndrome is about 14 days (the range is a few days to > 10 weeks).

• The disease is not readily recognized in the primary care setting because its symptoms are similar to those of the flu, mononucleosis, and other common illnesses.

Testing Recommendations

The U.S. Centers for Disease Control and Prevention recommend the following HIV testing in health care settings:

• Routine, voluntary, opt-out HIV screening for all persons 13-64 years of age in health care settings. Testing is not based on risk factors.

• HIV screening of pregnant women as part of the routine panel of prenatal screening tests. Testing is not based on risk factors.

• Repeat HIV screening of persons with known risk at least annually:

• Injection drug users and their sex partners

• Persons who exchange sex for money or drugs

• Sex partners of HIV-infected persons

• Men who have sex with men

• Heterosexual persons who themselves or whose sex partners have had more than one sex partner since their most recent HIV test

Pathophysiology

HIV is a retrovirus that replicates in and destroys CD4 cells. The result is a chronically deteriorating immune system leading to opportunistic infections and eventual death. Seroconversion typically occurs about 3 weeks after the acute infection (the range is from 2 weeks to 6 months). Antibodies generally appear within 3 months of infection (the range is from 2 weeks to 6 months).

Transmission is through infected blood or hazardous body fluids, which can occur during the following activities:

• Unprotected sexual contact with an infected person

• Multiple partners increase risk.

• Ongoing or past medical history of sexually transmitted disease increases risk.

• Sharing needles or syringes with an infected person

• Transfusions of infected blood or blood clotting factors (the United States began screening the blood supply in 1985)

• Vertical transmission (infected mother to infant)

• Breast-feeding

Occupational exposure and household contact are rare.

Diagnostic Criteria

Enzyme-linked immunosorbent assay

Enzyme-linked immunosorbent assay (ELISA) is the initial screening test for detection of anti-HIV antibodies. False-positive results can occur in patients with

• Collagen vascular diseases

• Chronic hepatitis

• Other chronic diseases

Western blot

All positive ELISA tests must be confirmed by a Western blot. Specificity and sensitivity of the Western blot is > 99%. The Western blot tests for anti-HIV antibodies.

Other tests

Other diagnostic tests are available. All should be confirmed by a Western blot.

Rapid diagnostic tests can give results from a finger stick or swab of oral fluid in 5-20 minutes.

Monitoring Tools

Viral load

Viral load testing measures the amount of virus in blood. It can assess disease progression and evaluate efficacy of antiretroviral therapy. Its lower limit of detection is less than 50 copies/mL for ultrasensitive assays (less than 400 copies/mL for nonultrasensitive assays). A minimally significant change in viral load is considered to be a threefold or 0.5log10 increase or decrease.

Acute illness and immunizations can cause increases in viral load for 2-4 weeks. Testing should not be performed during this time.

Baseline viral loads are established by averaging two viral loads (that do not differ by > 0.5log10) taken 2-4 weeks apart.

Monitoring of viral load in patients not on antiretroviral therapy should occur every 3-4 months. Monitoring of viral load in patients starting a new regimen should occur 2-8 weeks after treatment initiation and then every 3-4 months.

CD4 cell count

CD4 cell count indicates the extent of immune system damage and the risk of developing opportunistic infections. Normal CD4+ cell counts are 800-1,200 cell/mm3.

CD4+ cell counts should be measured every 3-4 months in patients on or off antiretroviral therapy. A 30% increase or decrease in CD4+ cells from baseline is considered significant.

Treatment Principles and Goals

Goals of therapy

Therapy has the following goals:

• Maximal and durable suppression of viral load

• Restoration or preservation of immunologic function

• Improvement in quality of life

• Reduction of HIV-related morbidity and mortality

Factors involved in achieving goals of therapy are as follows:

• Adherence to the antiretroviral regimen

• Rational sequencing of drugs

• Preservation of future treatment options

• Use of resistance testing in selected clinical settings

See

Table 31-1 for indications for the initiation of antiretroviral therapy in the chronically HIV-1 infected patient.

Guidelines for prevention and treatment and medications used for the treatment of HIV can be located as a living document at www.aidsinfo.nih.gov, which is updated three or four times a year.

Indications for Consideration of Changing Antiretroviral Therapy

Consider changing antiretroviral therapy (ART) with failure to suppress plasma HIV RNA (ribonucleic acid) to undetectable levels (< 50 copies/mL) within 4-6 months of initiating a therapy.

Consider changing ART if virus is detected in plasma repeatedly following initial suppression to undetectable levels.

[Table 31-1. Indications for the Initiation of Antiretroviral Therapy in the Chronically HIV-1 Infected Patient]

Consider genotyping or phenotyping to assist in identifying drugs for the next regimen if

• Adherent to failing regimen for at least the previous 4-6 weeks or within 4 weeks after regimen discontinuation

• Viral load above 1,000 copies/mL

Consider changing ART if CD4+ T cell numbers persistently decline, as measured on at least two separate occasions.

Consider changing ART if patient evidences clinical deterioration.

Never change just one medication in a failing regimen (i.e., use at least two new drugs, and preferably an entirely new regimen).

Change one medication in a successful regimen if a patient is experiencing intolerable side effects or if the medication has overlapping toxicity with other medications.

Use the treatment history and past and current resistance test results to identify active agents (preferably two or more) to design a new regimen.

31-2. Drug Therapy

Introduction

See

Table 31-2 for antiretroviral agents recommended by the U.S. Department of Health and Human Services for initial treatment of established HIV infection.

Nucleoside Reverse Transcriptase Inhibitors

Nucleoside reverse transcriptase inhibitors (NRTIs) are described in

Table 31-3. The mechanism of action of NRTIs is to interfere with HIV viral RNA-dependent DNA (deoxyribonucleic acid) polymerase, resulting in chain termination and inhibition of viral replication.

Didanosine, stavudine, and lamivudine are dosed on the basis of weight. Most NRTIs are not affected by food (except didanosine). NRTIs have a low pill burden as a class and few drug interactions. All are prodrugs requiring two or three phosphorylations for activation.

Four combination products are available:

• Combivir (zidovudine 300 mg + lamivudine 150 mg) every 12 hours

• Trizivir (zidovudine 300 mg + lamivudine 150 mg + abacavir 300 mg) every 12 hours

• Truvada (tenofovir 300 mg + emtricitabine 200 mg) every 24 hours

• Epzicom (lamivudine 300 mg + abacavir 600 mg) every 24 hours

[Table 31-2. Antiretroviral Regimens for Treatment of HIV Infection in Antiretroviral-Naive Patients]

No special storage requirements are necessary for drugs in this class.

Usually, two NRTIs are used in combination with one non-nucleoside reverse transcriptase inhibitor (NNRTI) or one protease inhibitor (PI).

Monitor for signs and symptoms of the following class toxicities:

• Lactic acidosis

• Severe hepatomegaly with steatosis

The following precautions should be kept in mind regarding NRTIs:

• Most patients should be dose-adjusted for renal impairment (exception: abacavir).

• Lamivudine and emtricitabine are chemically similar and should not be used in the same regimen.

• Do not use zidovudine with stavudine because of antagonism (both require thymidine for activation).

• Do not use didanosine with stavudine during pregnancy because of increased risk of lactic acidosis and liver damage.

• Tenofovir increases didanosine levels and decreases atazanavir levels. Dosage adjustments are required.

• Patients should be tested for HLA-B*5701 to determine risk for hypersensitivity reaction to abacavir. Only negative patients should start abacavir.

• The "D" drugs (ddI [didanosine] and d4T [stavudine]) can cause pancreatitis and peripheral neuropathy; when used together, this effect can be additive.

• The "D" drugs are more closely associated with lactic acidosis.

Non-nucleoside Reverse Transcriptase Inhibitors

NNRTIs are described in

Table 31-4. Their mechanism of action is to competitively inhibit reverse transcriptase, thereby resulting in inhibition of HIV replication.

One-step mutation (K103N) confers resistance to all NNRTIs but etravirine. All should be dose-adjusted for hepatic impairment.

Most are not affected by food (except efavirenz). Efavirenz is contraindicated in pregnancy.

Usually, one NNRTI should be used in combination with two NRTIs.

No special storage requirements are necessary for drugs in this class. Class toxicities include rash and hepatic toxicity.

Drug interactions can occur (see

Tables 31-5 and

31-6). All are cytochrome P450 (CYP450)-3A4 inducers or inhibitors.

[Table 31-3. Nucleoside Reverse Transcriptase Inhibitors]

[Table 31-4. Non-nucleoside Reverse Transcriptase Inhibitors]

[Table 31-5. Drugs That Should Not Be Used with NNRTIs]

[Table 31-6. Drug Interactions with NNRTIs Requiring Dose Modifications or Cautious Use]

Protease Inhibitors

Protease inhibitors (PIs) are described in

Table 31-7.

Their mechanism of action is to inhibit protease, which then prevents the cleavage of HIV polyproteins and subsequently induces the formation of immature noninfectious viral particles.

All should be dose-adjusted for hepatic impairment. Most should be taken with food (except fosamprenavir, tipranavir, lopinavir-ritonavir tablets, and indinavir). Atazanavir and indinavir require normal acid levels in the stomach for absorption.

Ritonavir is the most potent inhibitor in the class and is primarily used for intensification of other PIs. Ritonavir and tipranavir should be refrigerated.

Goals of intensification are as follows:

• Decrease pill burden

• Decrease frequency of doses (i.e., decrease from q8h to q12h)

• Increase drug levels, resulting in decreased resistance

[Table 31-7. Protease Inhibitors]

Class toxicities are as follows:

• Fat maldistribution

• Hyperglycemia

• Hyperlipidemia

• Hypertriglyceridemia

• Possible increased bleeding episodes in patients with hemophilia

Baseline PI monitoring is done 4-6 weeks after starting the PI. Monitoring should then take place every 3-6 months thereafter. The following tests are required:

• Glucose test

• Liver function tests (LFTs)

• Total cholesterol panel (particularly triglycerides)

• Signs and symptoms of gastrointestinal (GI) side effects

• Signs and symptoms of fat redistribution

Usually, one PI (boosted PIs preferred) is used in combination with two NRTIs.

All are CYP450-3A4 inhibitors, and drug interactions are typical of CYP450-3A4 inhibitors. See

Tables 31-8 and

31-9 for more information about drug interactions.

Entry inhibitors

Entry inhibitors include enfuvirtide (T20) and maraviroc. Enfuvirtide is a fusion inhibitor, whereas maraviroc is a CCR5 (chemokine [C-C motif] receptor 5) antagonist. See

Table 31-10 for information.

Enfuvirtide (T20) (Fuzeon)

Enfuvirtide's mechanism of action is to bind to glycoprotein 41 on the HIV surface, thus inhibiting HIV binding to the CD4 cell.

The dose is 90 mg subcutaneous every 12 hours. Side effects include injection-site reactions, an increased rate of bacterial pneumonia, and hypersensitivity.

Enfuvirtide is generally reserved for deep salvage regimens. Preferably, it should be used with at least two other active drugs. Resistance develops quickly with less potent regimens and in cases of poor adherence.

No known significant drug interactions have been seen to date. Enfuvirtide can be taken without regard to meals. It should be stored at room temperature; the reconstituted form should be stored in the refrigerator, where it will be stable for 24 hours.

Maraviroc (Selzentry)

Maraviroc's mechanism of action is to bind to CCR5 receptors on the CD4 cell surface, which inhibits HIV binding and entry into the CD4 cell.

Perform Trofile testing before using maraviroc to determine patient's tropism. The patient must be CCR5 tropic only.

Maraviroc is a CYP450-3A4 substrate. The dose depends on drug reactions:

• Use 150 mg po every 12 hours when giving maraviroc with strong CYP3A4 inhibitors (most PIs).

• Use 300 mg po every 12 hours when giving maraviroc with enfuvirtide, tipranavir-ritonavir, nevirapine, or weak CYP3A4 inhibitors.

• Use 600 mg po every 12 hours when giving with CYP3A4 inducers (efavirenz, rifampin, etc.).

Side effects include abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, and orthostatic hypotension.

Preferably, use maraviroc with at least two other active drugs. Take it without regard to meals.

Integrase inhibitors

Integrase inhibitors include raltegravir, which is marketed under the trade name Isentress (Table 31-10). Its mechanism of action is to block activity of the integrase enzyme, thereby preventing HIV DNA from meshing with the CD4 cell DNA. Metabolism is through UDP-glucuronosyltransferase 1A1 (UGT1A1) mediated glucuronidation

Drug interactions occur with rifampin and other drugs that effect UGT1A1. The dose is 400 mg po every 12 hours. Side effects include nausea, headache, diarrhea, pyrexia, creatinine phosphokinase (CPK) elevation. Preferably, raltegravir should be used with at least two other active drugs. Take it without regard to meals.

Potential Benefits of Early Therapy

• Maintenance of a higher CD4 count and prevention of potentially irreversible damage to the immune system

• Decreased risk for HIV-associated complications that can sometimes occur at CD4 counts greater than 350 cells/mm3, including tuberculosis, non-Hodgkin's lymphoma, Kaposi's sarcoma, peripheral neuropathy, human papillomavirus-

[Table 31-8. Drugs That Should Not Be Used with PIs]

[Table 31-9. Drug Interactions with PIs Requiring Dose Modifications or Cautious Use]

   associated malignancies, and HIV-associated cognitive impairment

• Decreased risk of nonopportunistic conditions, including cardiovascular disease, renal disease, liver disease, and malignancies and infections that are not associated with AIDS

• Decreased risk of HIV transmission to others, which will have positive public health implications

Potential Risks of Early Therapy

• Development of treatment-related side effects and toxicities

• Development of drug resistance because of incomplete viral suppression, resulting in loss of future treatment options

• Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence to therapy

• Increased total time on medication, with greater chance of treatment fatigue

• Premature use of therapy before the development of more effective, less toxic, or better-studied combinations of antiretroviral drugs

• Transmission of drug-resistant virus in patients who do not maintain full virologic suppression

Counseling

All patients should be counseled on the importance of adherence. Greater than 95% adherence is necessary to decrease the incidence of resistance. Patients should be given tools to facilitate adherence to complicated regimens (e.g., pillboxes, calendars, pagers, etc).

Patients should be counseled on class side effects, especially any that are unique or potentially serious.

Antiretroviral Therapy in the HIV-Infected Pregnant Woman

Highly active antiretroviral therapy (HAART) should be offered if the patient is not already receiving treatment:

• Avoid efavirenz.

• Avoid combining stavudine and didanosine.

• Consider starting treatment after the first trimester.

Continue current combination regimens (preferably with zidovudine) if the patient is already receiving therapy. Doing so decreases the risk of transmission from 30.0% to 2.5%.

Zidovudine alone can decrease risk of transmission when taken during pregnancy. The mother should also receive IV zidovudine during labor. The infant should receive 6 weeks of zidovudine (

Table 31-11).

Single-dose nevirapine given at onset of labor in women who have had no prior ART and given once to the infant between 48 and 72 hours of age has been shown to decrease the transmission rate. This treatment can also result in resistance to nevirapine, which negatively affects future treatment options for the mother.

Guidelines for prevention of vertical transmission can be located as a living document at www.aidsinfo.nih.gov, which is updated three or four times a year.

[Table 31-10. Integrase and Entry Inhibitors]

Postexposure Prophylaxis

General guidelines

Universal precautions should be taken. The most common infectious exposure is needlesticks or cuts (1 in 300 risk). The risk with mucous membrane exposure is much lower (1 in 1,000 risk).

Postexposure prophylaxis (PEP) can reduce HIV infection by about 80%. Start therapy within 1-2 hours of exposure. The length of therapy is 4 weeks.

Guidelines for PEP can be located as a living document at www.aidsinfo.nih.gov, which is updated three or four times a year. See also

Tables 31-12 and

31-13.

Nonoccupational PEP

Patients with exposure to HIV from a known positive source, such as sexual exposure or injection drug use, should receive nonoccupational PEP (nPEP) within 72 hours of the exposure. The length of therapy is 28 days.

Figure 31-1 provides an algorithm for evaluation and treatment when nonoccupational exposure occurs.

Table 31-14 describes nPEP antiretroviral regimens.

[Table 31-11. AIDS Clinical Trials Group 076 Guidelines: Dosing of Zidovudine for Prevention of Vertical Transmission]

Opportunistic Infections

Only two opportunistic infections require primary prophylaxis:

• Pneumocystis jiroveci pneumonia (PCP): Treatment is required when CD4+ cells fall below 200/mm3. The treatment of choice is trimethoprim-sulfamethoxazole (TMP-SMX) DS po qd (see

Table 31-15 for alternatives).

• Mycobacterium avium complex bacteremia (MAC): Treatment is required when CD4+ cells fall below 50/mm3. Azithromycin 1,200 mg po every week is the treatment of choice.

All other primary prophylaxis occurs only if the patient is antigen-positive or at high risk of exposure to the causative factor. All other opportunistic infections are treated when the patient is diagnosed. After treatment, patients receive suppressive therapy.

Some primary and secondary prophylaxis could possibly be discontinued with immune reconstitution (undetectable viral load and an increase in CD4 cells in response to ART; see Table 31-15).

Immune reconstitution inflammatory syndrome in response to existing or indolent opportunistic infections can sometimes occur when ART is started.

Guidelines for prophylaxis and treatment of opportunistic infections can be located as a living document at www.aidsinfo.nih.gov.

31-3. Prevention Guidelines

• Abstain from sex with an infected person.

• Ask about the sexual history of current and future sex partners.

• Reduce the number of sex partners to minimize the risk of HIV infection.

• Always use a latex condom from start to finish during any type of sex (vaginal, anal, or oral).

• Use only water-based lubricants.

• Avoid alcohol, illicit drugs, and sharing of needles (or syringes, cookers, or other drug paraphernalia).

• Do not share personal items such as toothbrushes, razors, or any devices used during sex. Such items may be contaminated by blood, semen, or vaginal secretions.

• Do not donate blood, plasma, sperm, body organs, or tissues if you are infected with HIV or have engaged in sex or needle-sharing behaviors that are risk factors for infection with HIV.

31-4. Hematologic Complications

Anemia can occur in HIV-infected patients. Causes include the following:

• HIV infection of marrow progenitor cells

• Drug-induced marrow suppression (zidovudine, ganciclovir, amphotericin, ribavirin, pyrimethamine, interferon, TMP-SMX)

Treatment of anemia is described in

Figure 31-2.

31-5. Key Points

• HIV is a virus that destroys the immune system.

• AIDS is caused by HIV and is defined as a CD4+ cell count less than 200/mm3 or the presence of an opportunistic infection.

• Acute retroviral syndrome occurs in 50-90% of patients within the first 2-4 weeks of infection with HIV.

• The viral load indicates the amount of virus in the body and is an indication of how well antiretroviral medications are working.

• The CD4+ cell count refers to the status of the immune system and how much a patient is at risk for developing an opportunistic infection.

• NRTIs, NNRTIs, PIs, entry inhibitors (fusion inhibitors, CCR5 antagonists), and integrase inhibitors are the currently available classes of medications used to treat HIV.

[Table 31-12. Recommended HIV PEP Treatment Options]

[Table 31-13. Regimens for PEP]

[Figure 31-1. Algorithm for Evaluation and Treatment of Nonoccupational Exposure]

[Table 31-14. nPEP Antiretroviral Regimens]

[Table 31-15. Opportunistic Infections]

[Figure 31-2. Guidelines for the Treatment of Anemia in the HIV Patient]

• Vertical transmission is prevented by treating the mother with HAART (preferred) or zidovudine alone.

• Pneumocystis jiroveci pneumonia requires primary prophylaxis at CD4+ cell counts < 200/mm3. TMP-SMX is the preferred treatment.

• Mycobacterium avium complex requires primary prophylaxis at CD4+ cell counts < 50/mm3. Azithromycin is the preferred drug.

• All other opportunistic infections require treatment followed by secondary prophylaxis.

31-6. Questions

Use the following case study to answer questions 1-4:

C. T. is a 23-year-old HIV-positive female who presents to the emergency department with shortness of breath and a fever. Physical exam reveals a temperature of 102°F, heart rate of 100 bpm, and decreased breath sounds in the left lower lobe of lungs. Chest x-ray is positive for infiltrates in the left lung. She is diagnosed with PCP. She has no previous history of opportunistic infections and is not on any medications at this time (she has not been seen by a health care provider in over a year). Her CD4+ count is 13 cells/mm3 and viral load is 170,198 copies/mL.

1.

What is the treatment of choice for C. T.'s PCP?

A. TMP-SMX DS 2 tabs po q8h for 21 days, then 1 tab po daily

B. Azithromycin 500 mg po on day 1, then 250 mg po daily indefinitely

C. Doxycycline 100 mg po twice daily for 7 days, then 100 mg po daily

D. Clarithromycin 500 mg po twice daily for 10 days, then 250 mg po daily

E. Vancomycin 1 g IV q12h for 10 days, then TMP-SMX DS po daily

 

2.

Should C. T. receive any other prophylaxis against opportunistic infections?

A. Yes, against MAC: Zithromax 1,200 mg po weekly

B. Yes, against thrush: Diflucan 100 mg po daily

C. Yes, against toxoplasmosis: Bactrim DS 1 tab po every Monday, Wednesday, and Friday

D. Yes, against CMV: Valcyte 450 mg po every Monday, Wednesday, and Friday

E. No

 

3.

Six weeks later C. T. presents to the HIV clinic for follow-up. Her CD4+ count is 12 cells/mm3 and viral load is 140,202 copies/mL. Should C. T. be started on HIV therapy?

A. Yes; her CD4+ cell count is < 200 cells/mm3 and she has had an opportunistic infection.

B. Yes; her viral load is greater than 100,000 copies/mL.

C. Yes; her Western blot was positive for HIV.

D. Yes; all patients with HIV should be treated as soon as the diagnosis is made.

E. No.

 

4.

C. T. wishes to be started on HIV therapy. Which of the following would be an appropriate regimen?

A. Zidovudine + efavirenz + nelfinavir

B. Zidovudine + stavudine + indinavir

C. Stavudine + didanosine + fosamprenavir

D. Tenofovir + emtricitabine + atazanavirritonavir

E. Nelfinavir + indinavir + fosamprenavir

 

5.

HIV can be transmitted by

A. unprotected sexual contact with an infected person.

B. sharing needles or syringes with an infected person.

C. infected mother to infant (vertical transmission).

D. transfusion of blood (before 1985).

E. all of the above.

 

6.

M. J. is 13 weeks pregnant and just tested positive for HIV. Her viral load is 22,434 copies/mL and her CD4+ cell count is 425 cells/mm3. M. J. wishes to receive treatment for her HIV. Which of the following would be an appropriate regimen for M. J.?

A. Zidovudine + stavudine + indinavir

B. Zidovudine + lamivudine + lopinavir-ritonavir

C. Zidovudine + lamivudine + efavirenz

D. Stavudine + didanosine + nevirapine

E. No treatment is necessary.

 

7.

Which of the following antiretroviral medications has shown efficacy as monotherapy in decreasing the vertical transmission of HIV?

A. Efavirenz

B. Nelfinavir

C. Zidovudine

D. Zalcitabine

E. Stavudine

 

8.

R. C. is a nurse in the emergency department. She has just been stuck with a needle that was used for an HIV-positive patient with a known high viral load. Which of the following is true concerning postexposure prophylaxis?

I. The regimen should be started within 2 hours of exposure.

II. R. C. will need to be treated only with zidovudine.

III. R. C. will need to be treated with a combination of zidovudine + lamivudine + nelfinavir.

IV. Treatment will continue for 4 weeks.

A. I, III, and IV

B. II only

C. II, III, and IV

D. I and IV

E. I, II, and IV

 

9.

The CD4+ cell count relates to

I. the activity of the virus.

II. the status of the immune system.

III. how much a patient is at risk for acquiring an opportunistic infection.

IV. when the patient was infected.

V. time to death in treated patients.

A. IV and V

B. I, II, and III

C. II and III

D. II, III, and IV

E. I, II, and V

 

10.

The viral load relates to

A. the activity of the virus and efficacy of antiretroviral therapy.

B. the status of the immune system.

C. when the patient was infected.

D. how much a patient is at risk for acquiring an opportunistic infection.

E. time to death in a treated patient.

 

11.

S. J. presents to the emergency department with extreme flank pain with nausea and vomiting. He is diagnosed with a kidney stone. His past medical history is positive for HIV and diabetes. His medications include indinavir, lamivudine, didanosine, metformin, and dapsone. Which of his medications might have caused his kidney stone?

A. Indinavir

B. Lamivudine

C. Didanosine

D. Metformin

E. Dapsone

 

12.

L. L. comes to the clinic with a chief complaint of burning and tingling in his feet that started about 1 month ago. His current medications include nelfinavir, stavudine, lamivudine, sertraline, and gemfibrozil. Which medication might be causing this problem?

A. Nelfinavir

B. Stavudine

C. Lamivudine

D. Sertraline

E. Gemfibrozil

 

13.

S. E. presents to the emergency department with a 2-day history of extreme nausea, vomiting, and abdominal pain. Labs reveal elevations in amylase and lipase, and a diagnosis of pancreatitis is made. His medications include nevirapine, tenofovir, didanosine, and amitriptyline. Which of his medications could have caused his pancreatitis?

A. Nevirapine

B. Tenofovir

C. Didanosine

D. Amitriptyline

E. All of the above

 

14.

Which HIV medication should not be used until HLA-B*5701 testing has been performed to assess risk for hypersensitivity?

A. Efavirenz

B. Ritonavir

C. Zidovudine

D. Abacavir

E. Lamivudine

 

15.

C. J. is starting efavirenz, tenofovir, lamivudine, and TMP-SMX. What should C. J. be counseled about concerning efavirenz?

A. Anemia

B. CNS side effects

C. Neutropenia

D. Renal toxicity

E. Kidney stones

 

16.

Which of the following can cause hepatotoxicity and requires monitoring of liver enzymes at baseline, 2 weeks, 4 weeks, 6 weeks, and then monthly for the first 18 weeks of therapy?

A. Zidovudine

B. Zalcitabine

C. Lopinavir-ritonavir

D. Fosamprenavir

E. Nevirapine

 

17.

Which of the following can cause hyperglycemia, hyperlipidemia (particularly elevations in triglycerides), and lipodystrophy?

A. Lopinavir-ritonavir

B. Delavirdine

C. Didanosine

D. Abacavir

E. Lamivudine

 

18.

Lactic acidosis and hepatic steatosis have been reported with which of these antiretroviral medications?

A. Nevirapine

B. Efavirenz

C. Stavudine

D. Saquinavir

E. Nelfinavir

 

19.

The mechanism of action of nucleoside reverse transcriptase inhibitors is to

A. directly inhibit reverse transcriptase.

B. prevent entry of the proviral DNA into the nucleus of the CD4+ cell.

C. cause chain termination, resulting in a defective copy of proviral DNA.

D. prevent entry of HIV into the CD4+ cell.

E. prevent cleavage of the newly formed polypeptide chains into a viable HIV.

 

20.

The mechanism of action of non-nucleoside reverse transcriptase inhibitors is to

A. prevent cleavage of the newly formed polypeptide chains into viable HIV.

B. prevent entry of HIV into the CD4+ cell.

C. prevent entry of the proviral DNA into the nucleus of the CD4+ cell.

D. directly inhibit reverse transcriptase.

E. cause chain termination, resulting in a defective copy of proviral DNA.

 

21.

The mechanism of action of protease inhibitors is to

A. cause a defective copy of proviral DNA to be made.

B. prevent entry of the proviral DNA into the nucleus of the CD4+ cell.

C. prevent cleavage of the newly formed polypeptide chains into a viable HIV.

D. prevent entry of HIV into the CD4+ cell.

E. directly inhibit reverse transcriptase.

 

22.

Which of the following medications if used with atazanavir can result in decreased levels and effectiveness of atazanavir?

A. Loratadine

B. Tenofovir

C. Esomeprazole

D. Metoclopramide

E. Glipizide

 

23.

Which of the following opportunistic infections are the only ones requiring primary prophylaxis?

A. PCP and MAC

B. PCP and toxoplasmosis

C. MAC and histoplasmosis

D. MAC and CMV

E. PCP and thrush

 

24.

The antifungal of first choice for maintenance therapy after treatment of cryptococcal meningitis is

A. itraconazole.

B. fluconazole.

C. ketoconazole.

D. amphotericin B.

E. terbinafine.

 

25.

The first-choice antifungal for treatment of histoplasmosis is

A. itraconazole.

B. fluconazole.

C. ketoconazole.

D. caspofungin.

E. terbinafine.

 

31-7. Answers

1.

A. The treatment of choice for PCP is TMP-SMX in patients who are not allergic to sulfa medications. Duration of treatment is 21 days. Because this patient's CD4+ cell count is below 200 cells/mm3 and she has had PCP, she will require secondary prophylaxis once treatment is completed. Preferred prophylaxis is once-daily TMP-SMX DS.

 

2.

A. This patient's CD4+ cell count is below 50 cells/mm3; therefore, she requires primary prophylaxis against MAC. Zithromax is the drug of choice. Prophylaxis against other opportunistic infections is generally not required.

 

3.

A. Current guidelines state that any patient who has had an opportunistic infection or a CD4+ cell count less than 200 cells/mm3 should start treatment for HIV. This patient has had both.

 

4.

D. Most regimens contain two NRTIs and either one PI or one NNRTI. A includes one NRTI, one NNRTI, and one PI. E includes three PIs. Zidovudine and stavudine competitively inhibit each other and would not be used in the same regimen (thus, B is incorrect). Didanosine and stavudine should not be used together because of increased toxicity (which makes C incorrect).

 

5.

E. All items are important risk factors for transmission of HIV. Breast-feeding, history of sexually transmitted diseases, occupational exposure to HIV-infected fluids (rare), and household exposure to HIV-infected fluids (rare) are also risk factors.

 

6.

B. All HIV-positive pregnant women should receive treatment for HIV to decrease the risk of transmission to their offspring. Zidovudine and stavudine competitively inhibit each other and should not be used together. Efavirenz is teratogenic and should not be used in pregnancy. Stavudine and didanosine together are contraindicated in pregnancy because of increased risk of lactic acidosis and liver damage.

 

7.

C. Zidovudine and nevirapine are the only HIV medications that can reduce vertical transmission when used as monotherapy. Most practitioners treat with combination therapy because of the increased risk of resistance with monotherapy, which affects future choices of drug regimen.

 

8.

A. The approved regimens for postexposure prophylaxis are similar to those for treatment of HIV. Treatment should continue for 4 weeks and should start within 2 hours of exposure.

 

9.

C. CD4+ cell count describes the status of the immune system (i.e., how much a patient is at risk for acquiring an opportunistic infection).

 

10.

A. Viral load relates to the activity of the virus and efficacy of antiretroviral therapy. The goal of therapy is an undetectable viral load (< 50 copies/mL).

 

11.

A. Indinavir can cause kidney stones. Patients should drink at least 48 oz of water a day to decrease the risk of developing a kidney stone.

 

12.

B. The "D" drugs, d4T (stavudine) and ddI (didanosine), can cause peripheral neuropathy and pancreatitis.

 

13.

C. The "D" drugs, d4T (stavudine) and ddI (didanosine), can cause peripheral neuropathy and pancreatitis.

 

14.

D. HLAB5701 testing should be performed prior to use of abacavir to assess risk of hypersensitivity.

 

15.

B. Efavirenz can cause central nervous system (CNS) side effects such as dizziness, trouble sleeping, drowsiness, trouble concentrating, and unusual dreams during the first 2-4 weeks of treatment.

 

16.

E. All NNRTIs can cause hepatotoxicity. There have been rare reports of hepatotoxicity after just one dose of nevirapine. Liver enzymes should be monitored at baseline, 2 weeks, 4 weeks, 6 weeks, and monthly for the first 18 weeks of therapy.

 

17.

A. Class side effects of PIs include hyperglycemia, hyperlipidemia, fat maldistribution, and increased bleeding in hemophiliacs.

 

18.

C. Class side effects of NRTIs include lactic acidosis and hepatic steatosis.

 

19.

C. NRTIs affect reverse transcriptase by causing chain termination, resulting in a defective copy of proviral DNA.

 

20.

D. NNRTIs affect reverse transcriptase by directly inhibiting reverse transcriptase, resulting in less proviral DNA being made.

 

21.

C. PIs prevent cleavage of the newly formed polypeptide chains into viable HIV, resulting in an immature virus that is unable to infect other CD4+ cells.

 

22.

C. Atazanavir levels are decreased by proton pump inhibitors, H2 blockers, and antacids.

 

23.

A. PCP requires primary prophylaxis when the CD4+ cell count falls below 200 cells/mm3. The preferred medication is TMP-SMX. MAC requires primary prophylaxis when the CD4+ cell count falls below 50 cells/mm3. The preferred medication is azithromycin.

 

24.

B. Generally, cryptococcal meningitis is initially treated with amphotericin B during the induction phase and then fluconazole for the consolidation phase and maintenance therapy.

 

25.

A. Histoplasmosis is generally initially treated with amphotericin B or itraconazole for induction therapy and then itraconazole for maintenance therapy.

 

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