Continuing Education

Published through an educational grant from WYETH-AYERST LABORATORIES
TRENDS IN PHARMACY AND PHARMACEUTICAL CARE

An ongoing CE program of The University of Mississippi School of Pharmacy and DRUG TOPICS.
The University of Mississippi School of Pharmacy is approved by the American Council on Pharmaceutical
Education as a provider of continuing pharmaceutical education. Accredited in every state requiring CE. ACPE # 032-999-01-005-H02

This lesson is no longer valid for CE credit after 12/31/03.

CREDIT:

This lesson provides two hours of CE credit and requires a passing grade of 70%.

OBJECTIVES:

Upon completion of this article, the pharmacist should be able to:

• Evaluate treatment options in HIV management

• Identify toxicities associated with antiretroviral therapy

• Understand the impact of adherence on therapeutic success

• Identify factors that affect adherence

• Evaluate therapy with lipid-lowering agents in HIV-infected patients

GOAL:

• To provide pharmacists with an overview of managing HIV disease

HIV/AIDS 2001:
Latest treatment strategies

By Billy Ray Brown, Pharm.D.

Clinical Assistant Professor, University of Mississippi School of Pharmacy, Consultant, Mississippi HIV Rural Area Network, University of Mississippi Medical Center and Marvin Robinson, Pharm.D. candidate University of Mississippi School of Pharmacy

According to the Tufts Centers for the Study of Drug Development at Tufts University, it takes an average of 15 years for an experimental drug to travel from a laboratory to a patient. Of the 5,000 compounds that enter preclinical testing, only five make it to human testing. Only one of those five is ultimately approved for sale by the Food & Drug Administration.

During 2000, there was one new protease inhibitor, lopinavir/ritonavir, approved by the FDA. The agency also approved the first triple-combination antiretroviral that consists of zidovudine, lamivudine, and abacavir sulfate. The year closed with the approval of a new formulation of didanosine. Much of the focus during the year was on better understanding the importance of adherence to antiretroviral regimens, simplifying regimens, evaluating antiretroviral toxicities, and managing concomitant disease states.

Current treatment approach

Three classes of antiretrovirals (ARVs) are approved by the FDA: Nucleoside reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). (See Table 1.) As new ARVs are envisioned, scientists are seeking ways to develop products that exhibit different resistance patterns and fewer adverse effects.

Table 1
Currently available antiretroviral agents

The Department of Health & Human Services' (DHHS) Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents were revised in February 2001 to reflect the importance of adherence in prescribing treatment regimens. Specific medications are recommended with consideration to pill burden, dosing frequency, food requirements, convenience, toxicity, and drug interaction profile. Table 2 highlights these recommendations, the goals of therapy being the following: maximal and durable suppression of viral load, restoration and/or preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. The new guidelines also reflect changes in the recommendations for initiation of therapy in asymptomatic HIV-infected patients. Current recommendations are to offer antiretroviral therapy to asymptomatic patients with CD4 counts less than 350 cells/mm³ and viral loads of any value. In asymptomatic patients with CD4 counts greater than 350 cells/mm³ and viral loads of greater than 30,000 (bDNA) or 55,000 (RT-PCR), it is also recommended that therapy be offered.

Table 2
Recommended initial antiretroviral therapy

Choosing an initial highly active antiretroviral therapy (HAART) can present a great challenge to health-care providers. Generally, the first regimen provides the best opportunity for achieving virologic and immunologic success. Additionally, this regimen should also preserve the efficacy of other antiretrovirals in case of the potential need to change regimens. Sequencing of antiretroviral regimens is paramount within drug classes as well as between drug classes. Whether contemplating a PI-based regimen, a NNRTI-based regimen, or a triple-NRTI regimen, advantages and disadvantages exist that make therapeutic decisions more challenging. Table 3 explores some of these advantages and disadvantages.

Table 3
Advantages and disadvantages of class-sparing regimens

*NRTIs ("nukes"). NRTIs are phosphorylated by cellular enzymes to the active triphosphate moiety. They then exert their action by competing with natural substrates for formation of proviral DNA by reverse transcriptase, thereby inhibiting viral replication. The currently available drugs in this class include: zidovudine, stavudine, didanosine, lamivudine, zalcitabine, and abacavir sulfate. Also available are two combination products: zidovudine + lamivudine; and zidovudine + lamivudine + abacavir sulfate.

The major adverse events associated with NRTIs are lactic acidosis and severe hepatomegaly with steatosis. There is a low frequency of occurrence but a high case fatality rate. Risk factors include female gender, obesity, and prolonged use of NRTIs. Currently, there are no data to suggest that the toxicities occur more often with any particular NRTI. The DHHS guidelines recommend suspending therapy if clinical or laboratory manifestations are suggestive of toxicity.

The FDA and the manufacturer of stavudine and didanosine recently issued cautionary letters to health-care professionals for the use of this combination therapy in pregnant women. There have been three reported cases of lactic acidosis, with or without pancreatitis, that occurred in pregnant women taking this combination with other antiretrovirals. Lactic acidosis occurs when body cells are unable to convert food into usable energy; consequently, excess acid accumulates in the body, and vital organs (i.e., liver or pancreas) are damaged. Although the data suggest that women may be at increased risk for the development of lactic acidosis and liver toxicity, it is not clear whether pregnancy potentiates these known adverse effects. The manufacturer recommends that the combination of the two drugs be used for pregnant women only when the potential benefit clearly outweighs the potential risk.

The manufacturer of didanosine produced two new formulations of this product during 2000. Early in the year, the company developed a 200-mg chewable/dispersible tablet that can be dosed only once a day. There is sufficient buffer in two tablets to protect this product from stomach acid degradation and allow it to pass to the small intestine for absorption. Later in the year, the company developed an enteric-coated capsule to be dosed once daily. The capsule contains enteric-coated beadlets that allow passage to the small intestine for absorption. Both the 200-mg tablet and the enteric-coated formulation require administration on an empty stomach. Because of limited data on long-term durability of response to a once-daily dosing regimen of didanosine, the preferred dosing regimen is twice daily with a buffered formulation. The manufacturer cautions that once-daily dosing with didanosine should be considered only for adult patients whose management requires once-daily administration or an alternative didanosine formulation.

The hypersensitivity reaction associated with abacavir sulfate is a very serious adverse event. It is characterized by skin rash, flu-like symptoms (e.g., fatigue, fever, nausea, muscle pain), vomiting, diarrhea, abdominal pain, and/or respiratory symptoms such as dyspnea, pharyngitis, or cough. The reaction has been observed in approximately 5% of patients. Symptoms usually occur within the first six weeks of treatment but may occur at any time during therapy. There have been reports that severe or fatal hypersensitivity reactions can occur within hours of reintroduction of abacavir sulfate in patients who have no history or unrecognized symptoms of hypersensitivity. The symptoms get progressively worse with continued treatment with abacavir sulfate but resolve following permanent discontinuation. Rechallenging patients with abacavir sulfate is contraindicated after a diagnosis of hypersensitivity. To avoid a delay in diagnosis and to minimize the risk of a life-threatening reaction, abacavir sulfate—or any product containing it—should be permanently discontinued if hypersensitivity cannot be ruled out.

The first triple-combination antiretroviral product was approved during the year 2000. The product contains abacavir sulfate, lamivudine, and zidovudine. This combination allows the convenience of administering one tablet twice a day without regard to food or water intake. It is indicated alone or in combination with other antiretroviral agents. It received approval for this indication based on analyses of data from a 24-week controlled study. There are currently no results from controlled studies analyzing long-term suppression of HIV or disease progression. There are also limited data on the use of this product in patients with viral loads greater than 100,000 copies/ml at baseline. It should not be prescribed for adults or adolescents weighing less than 40 kilograms or patients requiring dose adjustment. This combination product must not be used in patients who have experienced a hypersensitivity reaction to abacavir.

*NNRTIs ("non-nukes"). NNRTIs bind directly to reverse transcriptase and block the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The currently available drugs in this class include: nevirapine, efavirenz, and delavirdine.

The major adverse event associated with NNRTI therapy is rash. Approximately 5% of the rashes are severe, and there have been potentially fatal cases of Stevens-Johnson syndrome reported.

Nevirapine has received considerable attention for reports of severe, life-threatening, and sometimes fatal hepatotoxicity. Clinical presentation varied among patients. However, frequently occurring events included fatigue, malaise, anorexia, and nausea, with or without abnormal serum transaminase levels. The manufacturer recommends intensive clinical and laboratory monitoring during the first 12 weeks of therapy. Some experts recommend monitoring liver function tests (LFTs) at baseline, prior to dose escalation, and at two weeks post dose escalation. Although most events occurred during the first 12 weeks of therapy, approximately one-third of the cases occurred after 12 weeks.

Delavirdine is being studied for its potential pharmacoenhancing properties. It is an inhibitor of the cytochrome P450 system (CYP450), which may allow it to be used to decrease pill burden with PIs. More studies are warranted to evaluate the impact of drug-drug interactions when combining delavirdine with PIs.

*Protease inhibitors. PIs bind to the active site of HIV-1 protease and prevent the processing of viral gag and gag-pol polyprotein precursors. This results in the formation of immature, noninfectious viral particles. The currently available drugs in this class include: saquinavir soft gel capsules (SGCs), saquinavir hard gel capsules (HGCs), indinavir, ritonavir, nelfinavir, amprenavir, and lopinavir/ritonavir.

The major adverse events associated with PI therapy are hyperglycemia, fat redistribution, and hyperlipidemia. Because of limited data, recommendations for monitoring and intervention are unclear.

There have been reports of hyperglycemia, new-onset diabetes mellitus, diabetic ketoacidosis, and exacerbation of existing diabetes mellitus in patients receiving PI therapy. Onset of symptoms occurs at a median of 63 days following initiation of therapy. Hyperglycemia resolved in some patients who discontinued PI therapy. Some patients continued PI therapy and were treated with oral hypoglycemic agents or insulin. Most experts recommend continuing HAART in the absence of severe, life-threatening diabetes.

Changes in body fat distribution (lipodystrophy syndrome, pseudo-Cushing's syndrome) are characterized by central obesity and peripheral fat wasting. These changes may also include visceral fat accumulation, dorsocervical fat accumulation (buffalo hump), extremity wasting with venous prominence, facial thinning, and breast enlargement. Similar findings have also been reported in patients not receiving PI therapy.

Protease inhibitors have been hypothesized to cause dyslipidemia by impairing the generation of cis-9-retinoic acid (cis-9-RA). It is believed that this is accomplished either by direct binding to cytoplasmic retinoic acid binding protein type 1 (CRAB-1) or by inhibition of CYP450 3A isoforms that metabolize retinoic acid to cis-9-RA. The conversion of retinoic acid to cis-9-RA is a key step in lipid metabolism. As a result, there is reduced retinoic X receptor (RXR) stimulation, which leads to apoptosis and impaired differentiation of peripheral adipocytes.

Cases of hyperlipidemia have occurred with or without clinical findings of fat redistribution. All PIs have been implicated, but ritonavir appears to cause the highest frequency of occurrence of sustained increases in triglycerides and cholesterol. These sustained increases are of concern because of the possible association with cardiovascular events and pancreatitis. DHHS guidelines recommend initiating therapy for hyperlipidemia when triglyceride levels are >750 -1000 mg/dl and/or LDL cholesterol levels >130 mg/dl in individuals without known coronary disease and with two or more coronary risk factors. Or, initiate therapy for LDL cholesterol >160 mg/dl in individuals without known coronary disease and with fewer than two coronary risk factors.

The manufacturer of amprenavir issued labeling changes for the oral solution preparation to address the potential risk of toxicity from intake of large amounts of propylene glycol that is used in the formulation to achieve adequate solubility. The alcohol and aldehyde dehydrogenase enzyme pathway metabolizes propylene glycol. Because this enzyme pathway does not attain full activity until 12 to 30 months of age, some young patients may not be able to adequately metabolize and eliminate propylene glycol. The oral solution is therefore contraindicated in infants and children below the age of four, pregnant women, patients with hepatic or renal failure, and patients treated with disulfiram or metronidazole. Asians, Eskimos, Native Americans, and women may also be at increased risk of propylene glycol-associated adverse events. Seizures, stupor, tachycardia, lactic acidosis, renal toxicity, hyperosmolality, and hemolysis characterize these events. Health-care providers should consider using the capsule formulation of amprenavir or an alternate PI.

The first double-PI combination antiretroviral received FDA approval during the year 2000. Lopinavir/ritonavir offers the convenience of twice-daily dosing. Each capsule contains 133 mg of lopinavir and 33 mg of ritonavir. The oral solution contains 80 mg of lopinavir and 20 mg of ritonavir per milliliter. Both formulations require refrigeration. The oral solution contains 42.4% alcohol (v/v). It is highly protein-bound (98%-99%) and is metabolized almost exclusively by CYP3A isozymes. It inhibits CYP3A and, to a lesser extent, CYP2D6. Administration with food maximizes absorption. Most common adverse effects include diarrhea, nausea, vomiting, abdominal pain, asthenia, headache, and rash. Preliminary data suggest that lopinavir/ritonavir may have activity against some PI-resistant strains, as well as a favorable side effect profile.

Role of adherence

Adherence denotes a therapeutic partnership between a patient and a health-care provider. According to a study by D. L. Paterson and colleagues, it appears that adherence levels of 95% and higher are necessary to avoid virologic failure in the majority of patients. Virologic failure was defined as >400 viral copies/ml. In their study of 81 patients, virologic failure was seen in 80% of patients with less than 80% adherence, 61% of patients with adherence levels between 80% and 95%, and 22% of patients with adherence levels of 95% and higher.

There currently is no gold standard for predicting or measuring adherence. Studies have shown that physicians erred in their predictions of adherence 41% to 50% of the time. Age, race, gender, educational level, socio-economic status, and history of substance abuse are poor predictors of nonadherence. Even when substance abusers are separated into active users and past users, variability in the rates of adherence still exists. However, there is a tendency for substance abuse to mask depression. Studies have shown that depression and other undiagnosed or untreated affective disorders are major obstacles to achieving optimal adherence.

There have been a number of methods proposed for assessing adherence. Patient self-reporting is among the simplest and most cost-effective; however, results are less accurate due to patient overestimation of adherence. Medication Event Monitoring Systems (MEMS) represent the more sophisticated and more costly methods. It serves not only as a monitoring device; it also serves to enhance adherence. Other methods of monitoring adherence are outlined in Table 4.

Table 4
Methods for measuring adherence

Factors that potentially affect adherence can be divided into four categories: patient factors, system of care, provider-patient relationship, and treatment regimen. Table 5 outlines some methods of intervention that have been shown to improve adherence as it relates to these factors. Patient factors often represent situations outside the scope of practice of health-care providers. However, in order to achieve optimal therapeutic success, these factors must be addressed. Before prescribing antiretrovirals, a patient's readiness to begin therapy must first be established. His/her readiness could be impeded by life stresses, lack of knowledge about HIV, past experiences, coexisting morbidity, cultural and health beliefs, and lack of trust in the medical community. Both patient and health-care provider must understand that the first HAART regimen has the best chance of sustained effectiveness. Behavior and conditions that impede adherence eventually yield virologic failure.

Table 5
Methods of intervention to improve adherence

Engaging a system of care should not be a patient experience with deleterious consequences; a system of care should be easily accessible and provide a caring environment. As much as possible, continuity of care must be implemented in order to build a great provider-patient relationship. A patient should feel secure in the maintenance of his/her confidentiality. Health-care providers should consider periodic discussions about patient confidentiality among the office staff to ensure that patient rights are optimally protected.

The relationship between health-care providers and patients should be based on mutual trust and respect. A patient must be satisfied with the clinical skills of the health-care provider as well as the level of understanding he/she receives during communication. A patient also tends to feel more secure when the health-care provider or a team member is easily accessible.

Adhering to a treatment regimen can present special challenges to a patient. Quite often a regimen can pose an intrusion on a patient's lifestyle. Because of the high cost of medications, a patient may have to choose between obtaining medications and paying his/her utility bills. The number of medications, dosing frequency, timing with or without meals, and storage requirements represent other potential factors affecting adherence. Adverse drug events, whether perceived or experienced, can represent major impediments to adherence. However, extensive patient counseling before therapy is initiated should give a patient a sense of preparedness as well as a mechanism for managing potential adverse drug events.

Lipid management in HIV disease

Dyslipidemias, abnormalities of lipid metabolism, were described well before the advent of HAART. However, much debate has evolved since the appearance of dyslipidemia in HIV-infected patients on HAART. Early in HAART, some began to formulate links between the use of PIs and increased risk of heart attacks due to dyslipidemia. Currently, these linkages can be refuted because of the occurrence of dyslipidemia among patients on HAART that does not include a PI. Dyslipidemia has also been shown to occur among patients on NRTIs, namely stavudine and didanosine, although the mechanism is not known.

According to the Preliminary Guidelines for the Evaluation & Management of Dyslipidemia in HIV-Infected Adults Receiving Antiretroviral Therapy, HIV-infected patients should undergo evaluation and treatment based on the existing National Cholesterol Education Program (NCEP) guidelines, with the caveat that avoidance of drug interactions with antiretroviral agents is preeminent. It is recommended that a fasting lipid profile be obtained prior to HAART therapy, and this should be repeated within three to six months following the initiation of this treatment. The lipid panel should include the measurement of total cholesterol (TC), HDL cholesterol, and triglycerides (TG), with calculation of LDL. It is also recommended that patients be routinely screened for other cardiovascular risk factors (see Table 6).

Table 6
Risk status based on presence of CHD risk factors

Nondrug therapies should generally be instituted first before initiating lipid-lowering therapy. Smoking cessation and regular aerobic exercise are health measures that reduce TG and improve the overall cardiovascular risk profile. Weight reduction and decreased fat intake are strongly recommended if obesity is present. Dietary needs are complex in the HIV-infected population where the need for lipid lowering and weight gain may coexist. For many, it is preferable to manage the wasting phenomenon prior to their dyslipidemia.

Because of the potential drug-drug interactions with PIs and NNRTIs, caution should be exercised when initiating lipid-lowering therapy in HIV-infected patients. PIs and NNRTIs are extensively metabolized by CYP450 3A4 isoenzymes. Many of the lipid-lowering agents are also metabolized by CYP450 3A4 and therefore pose possible drug-drug interactions (see Table 7).

Table 7
CYP450 influence on lipid-lowering agents

Statins (3-hydroxy-3-methylglutaryl-coenzyme A or HMG-CoA reductase inhibitors) are the most commonly prescribed agents for treatment of hypercholesterolemia. The currently available products in this class include lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, and pravastatin. The DHHS guidelines recommend avoiding concomitant use of lovastatin and simvastatin with PIs and delavirdine. Both are lipophilic and are developed as prodrugs to concentrate active drug in the liver. The potential problems with concomitant use of the statins with PIs and delavirdine involve increased skeletal muscle toxicity due to increased levels of statins caused by CYP450 3A4 inhibition. Because of the development of rhabdomyolysis associated with elevated statin levels, the FDA has issued warnings about using statins concomitantly with agents that inhibit their metabolism. The use of initial low doses of the statins is recommended in HIV-infected patients who require drug therapy for hypercholesterolemia—preferably, either pravastatin (20 mg daily) or atorvastatin (10 mg daily). Fluvastatin and cerivastatin may serve as reasonable alternatives. Baseline LFTs should be performed before initiating therapy and monitored periodically.

When hypercholesterolemia is accompanied by elevated triglycerides, fibrates are good alternatives. The currently available drugs in this class include gemfibrozil and fenofibrate. Drug interactions with PIs and NNRTIs are unlikely, because the fibrates are not metabolized by the CYP450 3A isoenzymes. Health-care providers should also exercise caution with concomitant use of statins with fibrates because of the potential increase of skeletal muscle toxicity.

Resin (bile acid sequestrants) therapy (cholestyramine and colestipol) is often limited by associated adverse events, which include bloating, abdominal pain, gastro-esophageal reflux, and constipation. The lipid-lowering effect is also not as pronounced as other classes of lipid-lowering agents. The constipation effect could prove beneficial in HIV-infected patients encountering diarrhea. The preliminary guidelines for dyslipidemia discourage the use of resins because of their association with increased triglyceride levels.

Niacin is an essential B vitamin with good lipid-lowering properties. It is not metabolized by CYP450 3A4; therefore, it should not interact with PI or NNRTI therapy. When patients are receiving PI therapy, niacin should be avoided as first-line therapy because of its association with insulin resistance.

Dyslipidemia has emerged as an important complication of antiretroviral therapy. The preliminary guidelines recommend using the NCEP guidelines as a foundation to begin evaluation and therapy for HIV-infected patients with dyslipidemia. When choosing a lipid-lowering agent, health-care providers should be aware of drug-drug interactions associated with the concomitant use with some antiretrovirals.

*References (Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, DHHS, Feb. 5, 2001) are available upon request.

TEST QUESTIONS

Write your answers on the answer form below (photocopies of the answer form are acceptable) or on a separate sheet of paper. Mark only one correct answer.

1. Which one of the following is not an FDA-approved class of antiretrovirals?

a. Nucleoside reverse-transcriptase inhibitor
b. Nucleotide reverse-transcriptase inhibitor
c. Protease inhibitor
d. Non-nucleoside reverse-transcriptase inibitor

2. Which of the following represents the components of the first triple-combination antiretroviral product to receive FDA-approval?

a. Zidovudine/lamivudine/stavudine
b. Zidovudine/lamivudine/didanosine
c. Zidovudine/lamivudine/abacavir sulfate
d. Abacavir sulfate/lamivudine/stavudine

3. Which one of the following belongs to the class of nucleoside reverse-transcriptase inhibitors?

a. Zalcitabine
b. Delavirdine
c. Efavirenz
d. Nevirapine

4. Lactic acidosis and hepatomegaly are adverse events associated with which class of antiretrovirals?

a. Protease inhibitors
b. Non-nucleoside reverse-transcriptase inhibitors
c. Nucleotide reverse-transcriptase inhibitors
d. Nucleoside reverse-transcriptase inhibitors

5. Which one of the following dosage formulations of didanosine should be dosed only once-daily?

a. Didanosine 200-mg chewable/dispersible tablets
b. Didanosine 100-mg chewable/dispersible tablets
c. Didanosine 50-mg chewable/dispersible tablets
d. Didanosine 25-mg chewable/dispersible tablets

6. Which one of the following warrants permanent discontinuation after the presence of a hypersensitivity reaction?

a. Efavirenz
b. Abacavir sulfate
c. Stavudine
d. Nelfinavir

7. Rash is a class adverse event of which one of the following?

a. Non-nucleoside reverse-transcriptase inhibitors
b. Nucleoside reverse-transcriptase inhibitors
c. Fusion inhibitors
d. Integrase inhibitors

8. Which one of the non-nucleoside reverse-transcriptase inhibitors has been associated with a severe, life-threatening, and sometimes fatal hepatotoxicity?

a. Indinavir
b. Ritonavir
c. Nevirapine
d. Delavirdine

9. Protease inhibitors, as a class, are associated with all the following adverse events except:

a. Hyperglycemia
b. Hyperpigmentation of fingernails
c. Fat redistribution
d. Hyperlipidemia

10. Which protease inhibitor appears to cause the highest frequency of occurrence of elevated triglycerides and cholesterol?

a. Nelfinavir
b. Zalcitabine
c. Ritonavir
d. Indinavir

11. Propylene glycol toxicity is associated with which one of the following?

a. Stavudine oral solution
b. Amprenavir oral solution
c. Ritonavir oral solution \
d. Nevirapine oral solution

12. Which one of the following represents the first double-protease inhibitor combination product to receive FDA approval?

a. Ritonavir/saquinavir
b. Indinavir/ritonavir
c. Amprenavir/ritonavir
d. Lopinavir/ritonavir

13. What percentage of adherence is needed to avoid virologic failure in the majority of patients receiving antiretroviral therapy?

a. 95% and greater
b. 80% to 95%
c. 65% to 80%
d. Less than 65%

14. Studies show that physicians erred in their prediction of adherence by what percent?

a. Less than 5%
b. 5% to 10%
c. 80% to 90%
d. 41% to 50%

15. Which one of the following has been shown to be a major inhibitor to patients achieving optimal adherence?

a. Depression
b. Age
c. Race
d. Gender

16. The relationship between the patient and the health-care provider should represent which one of the following?

a. Provider dominance
b. Patient retentiveness
c. Mutual trust and respect
d. Provider discretion

17. The DHHS guidelines recommend avoiding the use of which of the following lipid-lowering agents in conjunction with protease inhibitors and delavirdine?

a. Simvastatin and lovastatin
b. Pravastatin and atorvastatin
c. Cerivastatin and fluvastatin
d. Gemfibrozil and atorvastatin

18. What is the potential problem with concomitant use of protease inhibitors and/or delavirdine with HMG-CoA reductase inhibitors?

a. Skeletal muscle toxicity
b. Insomnia
c. Constipation
d. Diarrhea

19. The Preliminary Guidelines for the Evaluation and Management of Dyslipidemia in HIV-Infected Adults Receiving Antiretroviral Therapy recommends avoiding which class of lipid-lowering agents because of the association with elevated triglyceride levels?

a. Statins
b. Niacin
c. Resins
d. HMG-CoA reductase inhibitors

20. Niacin should be avoided as first-line lipid-lowering therapy in patients receiving protease inhibitors because of its association with which one of the following?

a. Insulin resistance
b. Fat redistribution
c. Flushing
d. Rhabdomyolysis

 

Billy Ray Brown. HIV/AIDS 2001: Latest treatment strategies. Drug Topics 2001;6:39.