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This course will expire or be updated on or before March 3, 2014.
ABOUT THIS COURSE
You must score 70% or better on the test and complete the course evaluation to earn a certificate of completion for this CE activity.
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Wild Iris Medical Education, Inc. is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.
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Nurse practitioners may apply these contact hours to pharmacy continuing education and prescriptive authorization.
Wild Iris Medical Education, Inc. provides educational activities that are free from bias. The information provided in this course is to be used for educational purposes only. It is not intended as a substitute for professional health care. See our disclosures for more information.
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COURSE OBJECTIVE: The purpose of this course is to provide a review of the clinical manifestations and treatment of HIV/AIDS.
Upon completion of this course, you will be able to:
The trajectory between infection with HIV and the development of full-blown AIDS can be steep or gradual and may take as long as a decade or more. If the infection is untreated, the average time from HIV infection to death is 10 to 12 years. However, early detection and appropriate medical treatment may extend the lives of those infected and reduce the rates of HIV transmission.
As the HIV virus suppresses immune function, the infected person becomes more vulnerable to opportunistic infections caused by a wide variety of bacteria, viruses, fungi and other pathogens encountered in daily life. The physical results of these opportunistic infections are called clinical manifestations. For example, the opportunistic infection cytomegalovirus (CMV) often causes the clinical manifestation of blindness in people with AIDS.
Some conditions, called co-factors, can affect the course of disease progression, including age, genetic factors, drug use, smoking, nutrition, and coinfection with hepatitis C virus (HCV) and/or tuberculosis (TB).
Although the slope of the disease trajectory varies with each individual, HIV/AIDS progresses through five stages:
|Source: Zolopa & Katz, 2010.|
|Definitive AIDS diagnoses with or without laboratory evidence of HIV infection||
|Definitive AIDS diagnoses with laboratory evidence of HIV infection||
|Presumptive AIDS diagnoses with laboratory evidence of HIV infection||
HIV infection affects more than just the immune system. It also affects the cardiovascular, neurologic, and musculoskeletal systems as well as the body’s basic metabolism. These effects can alter:
Multisystem effects can lead to many painful or disruptive conditions, including:
Dementia is a growing concern as HIV-infected people live longer. Using functional MRI, researchers measured the blood flow in the brains of people with HIV and found signs of premature aging. Whether this effect is the result of the virus or the antiviral drugs—or both—is unclear. However, the evidence of harm raises concern because, by 2015, people over 50 will account for more than half of all AIDS patients (Ances et al., 2010).
HIV/AIDS also increases the risk of certain cancers, four of which are included in the CDC classification of AIDS: Kaposi’s sarcoma, non-Hodgkin’s lymphoma, primary lymphoma of the brain, and invasive cervical carcinoma in women. Recent research shows that in HIV-infected men, antiretroviral therapy has a protective effect against first AIDS-defining cancers (Shiels et al., 2008). Cervical carcinoma seems to be more aggressive in HIV-infected women. Most women with cervical cancer die of that disease rather than AIDS (Zolopa & Katz, 2010).
Research has also shown that HIV infection is associated with a five-fold increase in the incidence of Hodgkin’s disease. Anal dysplasia and squamous cell carcinoma have also been associated with HIV infection in both men and women, many of whom are also infected with HPV. Dysplasia can progress quickly to invasive cancer in patients with compromised immune systems; therefore, some experts recommend anal Papanicolau swabs in HIV patients.
Antiretroviral therapy (ART) has become the gold standard for treatment of HIV/AIDS. People with HIV may also receive medications to treat or prevent opportunistic infections, boost the immune system, and prevent anemia.
Antiretroviral drugs are administered in “cocktails” of three or more, a treatment referred to as antiretroviral therapy (ART). (ART is also sometimes referred to as highly active antiretroviral therapy, or HAART.) The primary goal of ART is to reduce HIV-associated morbidity and mortality by suppressing the individual’s viral load to below detectable levels.
Antiretroviral treatment of people with HIV continues to prove complex, controversial, dynamic, and expensive. These drugs do not constitute a “cure” for HIV/AIDS. If therapy is discontinued, viral load will increase. Even during treatment, the virus is replicating and the person remains infectious to others.
Five major classes of drugs are used to treat HIV/AIDS:
*CCR5 stands for chemokine (C-C motif) receptor 5, one of the two known points of entry used by the HIV virus to penetrate the CD4 T-cells. CCR5 antagonists are designed to block this receptor. The first of these drugs was approved by the FDA in August 2007 for use in treatment-experienced patients who have detectable HIV RNA and multidrug resistance to antiretrovirals.
**The first of these newest drugs, raltegravir (Isentress), was approved by the FDA on October 12, 2007. This class of drugs is designed to slow the progression of HIV by blocking the HIV integrase enzyme that the virus needs in order to multiply.
In 1996, tests to measure an individual’s viral load became available, providing objective criteria for treatment decisions. Following are treatment recommendations by the Panel on Antiretroviral Guidelines for Adults and Adolescents (2009):
Once ART has begun, CDC recommends these goals of therapy:
Treatment guidelines are revised frequently based on ongoing research findings. The most up-to-date information can be found online at http://aidsinfo/nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
|Source: Zolopa & Katz, 2010.|
|All HIV-infected individuals||
|HIV-infected individuals with CD4<200 cells/μL||P jiroveci prophylaxis|
|HIV-infected individuals with CD4<75 cells/μL||M avium complex prophylaxis|
|HIV-infected individuals with CD4<50 cells/μL||Consider CMV prophylaxis|
|PPD = purified protein derivative; INH = isonicotinic acid hydrazide (isoniazid); RPR = rapid plasma regain; VDRL = Venereal Disease Research Laboratories; IgG = immunoglobulin G; HBsAb = antibody to the hepatitis B surface antigen; CMV = cytomegalovirus|
The efficacy of ART can be measured by plasma HIV RNA testing. Four to six months after treatment begins, there should be no detectable virus (<50 copies/mL). Treatment failure at this point may be due to nonadherence, inadequate potency of drugs, suboptimal levels of antiretroviral agents, viral resistance, or other factors not completely understood.
Patients whose treatment fails despite careful adherence to the regimen should have their regimen changed. A thorough drug treatment history plus drug resistance testing should guide the design of the new regimen.
Patients who are cared for by clinicians with expertise in HIV/AIDS have better outcomes—in mortality, rate of hospitalizations, compliance with guidelines, cost of care, and adherence to medication regimens—than those cared for by less-experienced providers. Expertise is defined in terms of the number of patients actually managed. The DHHS panel recommends HIV primary care by a clinician with at least 20 HIV-infected patients and preferably at least 50 HIV-infected patients.
Many new medications for HIV/AIDS are in clinical trials. Patients experiencing drug resistance may be appropriate candidates for drugs still in trials. Physicians without extensive experience in treating HIV/AIDS are strongly urged to consult with specialists in this area when considering clinical trials for their patients.
The clinical management of HIV/AIDS is complex, comprising several major concerns. In 2010, a national multiagency collaboration consisting of the National Committee for Quality Assurance (NQA), American Medical Association (AMA), Health Resources and Services Administration (HRSA), Infectious Diseases Society of America (IDSA), and HIV Medicine Association (HIVMA) endorsed 17 measures for quality of HIV care (see below). All healthcare practitioners can use these benchmarks to assess the management of patients with HIV.
HIV CARE QUALITY MEASURES
Process of Care
* Pneumocystis jiroveci pneumonia
** antiretroviral therapy
Source: Hoberg et al., 2010.
Successful treatment not only requires the patient to have significant financial resources but also the ability to understand and comply with a complex regimen.
Unfortunately, many of the patients with the greatest need for treatment lack the necessary financial resources to make treatment a reality. However, patient demographics, such as race/ethnicity, sex, age, and socioeconomic status, do not predict who will adhere to a treatment regimen. Research in Africa among the poorest populations showed 90% adherence, as compared to 70% in the United States (McNeil, 2003).
Discontinuing or interrupting ART may become necessary due to factors such as serious drug toxicity, intervening illness, surgery, or unavailability of medications. Although unplanned short-term interruption of therapy may be unavoidable, planned interruption is no longer recommended. Interrupting therapy increases the risk of AIDS-related complications, declining CD4 counts, and other non-AIDS-related complications such as heart attack and liver failure.
While extending and improving lives of people with HIV, long-term use of some of these drugs increases the risk of liver problems, high cholesterol, stroke, heart disease, osteoporosis, diabetes, pancreatitis, neuropathy, and skin rashes. Some of the skin rashes can be life-threatening, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are two different forms of the same kind of skin rash. TEN may involve as much as 30% of the total body skin area. Both these severe rashes must be treated by a physician.
Antiretroviral drugs may also interact with other drugs used to treat opportunistic infections. For example, researchers reported that using oral erythromycin while taking protease inhibitors increased the risk of sudden death from cardiac causes (Ray et al., 2004). As patients live longer with HIV/AIDS, many develop drug-resistant strains of the virus, which further complicates treatment.
Use of multi-drug ART by many people over time has allowed drug-resistant strains of the virus to develop. These drug resistant strains have been found in those receiving ART as well as in patients who have never received ART, which limits their treatment options at the outset.
Experts predict that drug-resistant infections are about to spike in developed countries. One recent study suggests that drug resistance will increase by about 30% in the next 3 to 5 years in San Francisco (Smith et al., 2010). Treating drug-resistant HIV requires a constantly changing cocktail of expensive new drugs, and adherence to such a complex regimen can be difficult for many patients. If drug resistance increases in developing countries, treatment would be unsustainable.
Experts recommend that pretreatment drug resistance testing be done in persons with acute or chronic HIV infection and when changing antiretroviral regimens after drugs cease to be effective (treatment failure). Resistance testing helps clinicians better predict viral response to newly initiated therapy.
HIV drug resistance testing also should be performed:
In cases of virologic failure, drug resistance testing should be performed while the patient is taking his or her drugs or within 4 weeks of discontinuing therapy.
Two types of resistance assays are used: genotypic and phenotypic assays. Genotypic assays detect drug resistance mutations in the viral genes, while phenotypic assays measure a virus’s ability to grow in different concentrations of antiretroviral drugs. Genotypic assays take 1 to 2 weeks and phenotypic assays, 2 to 3 weeks. A genotypic assay is generally recommended for patients who have never had antiretroviral therapy. Genotypic resistance testing also is recommended for all pregnant women prior to initiation of therapy and for those entering pregnancy with detectable HIV RNA levels while on therapy.
Current recommendations for pregnant women are to start antiviral therapy during the second trimester. Those women who seek perinatal care after the second trimester should start treatment as soon as possible thereafter.
Therapy should be individualized for each woman based on her history of HIV antiretroviral therapy (past or current use or never used) as well as possible coinfection with HBV and/or HCV. Choice of therapy regimen also should consider not only the effectiveness of drug treatment for maternal disease but also possible teratogenic effects of the drugs on the infant. For example, efavirenz (EFV) should be avoided during the first trimester of pregnancy, and no pregnant woman should be offered regimens containing nelfinavir (NFV).
Public Health Service guidelines emphasize that combination drug regimens—rather than zidovudine (ZDV) alone—are considered the standard of care both for treatment of maternal HIV infection and for prevention of perinatal HIV transmission. Clinical trial results indicate that antiretroviral prophylaxis to prevent perinatal transmission of HIV should be offered to all HIV-infected women, regardless of CD4 cell count (Panel on Treatment of HIV-Infected Pregnant Women, 2010).
Specific detailed guidelines for the antepartum, intrapartum, and postpartum treatment of HIV-infected women of childbearing age and treatment of their infants evolve rapidly. Practitioners are advised to consult the most recent information on the CDC’s AIDSinfo website (Panel on Treatment of HIV-Infected Pregnant Women, 2010).
Smoking cessation is important for all women receiving ART because it interferes with the therapy’s effectiveness. A large, 8-year study of women showed that those who smoked were more likely than nonsmokers to die during the study period. Smokers also had higher viral loads and lower CD4 counts. They also were more likely to be diagnosed with an AIDS-related illness such as wasting syndrome or non-Hodgkin’s lymphoma (Feldman, 2006).
According to the Office of Women’s Health (2009), women taking antiviral drugs may have different side effects than men on the same drugs. This may be because women are generally smaller than men and have a higher body-fat content and different hormones. For example, ritonavir (Norvir, RTV) causes more nausea and vomiting in women but less diarrhea than in men.
Some women with HIV, especially those with a low CD4 count, experience irregular or long menstrual periods. Others may also experience early menopause and are more likely to have rashes, fat buildup, and problems with their pancreas and liver. However, more research is needed before treatment doses can change, and more clinical trials need to be done that include higher numbers of women.
Women with HIV may suffer discrimination by prescribing physicians. A study of HIV-infected patients in 10 U.S. cities showed that women were less likely than men to receive prescriptions for the most effective treatments for HIV infection (McNaghten et al., 2004).
In addition to ART, people with HIV/AIDS may also receive medications to treat or prevent opportunistic infections, boost the immune system, and prevent anemia. Some of these medications may have serious interactions with ART, so prescribing physicians need to be familiar with all ART medications, as well as with their potential toxicities, when administered with other drugs.
Some people with HIV supplement their prescription drugs with vitamins, acupuncture, massage, yoga, meditation, herbs, naturopathic remedies, and other complementary therapies. People who turn away from prescription HIV medications and choose only herbs, vitamins, and other supplements are said to be using alternative therapies. Many of these remedies have not been studied to see if they offer any real benefit.
Therapies such as yoga, meditation and massage can help reduce stress and enhance quality of life. However, herbs and other “natural” remedies may also interact with prescription medication. For example, St. John’s wort has major interactions with HIV medications. Therefore, people on HIV medications need to tell their physician, pharmacist, and social worker about all other supplements and nonprescription drugs they take.
Infections that are commonly found in HIV-positive patients include a number of other sexually transmitted diseases, TB, and hepatitis. Coexisting infections may increase the risk of transmission of HIV and make its treatment more complex.
Mycobacterium tuberculosis (M. tuberculosis, or TB) is the most common and most deadly coexisting infection for HIV-positive individuals. Likewise, the spread of HIV/AIDS has helped fuel the TB epidemic. The CDC estimates that TB is the cause of death for 1/3 of people with HIV worldwide. Any HIV-infected person with a diagnosis of TB should be reported as having TB and AIDS.
According to the CDC (2009d):
TB is transmitted by airborne droplets from people with active pulmonary or laryngeal TB during coughing, sneezing, or talking. When these infected droplets are inhaled, the bacteria enter the bloodstream and lymphatic system, and circulate throughout the body.
Most of the bacteria settle in the lungs, where they multiply and may cause pneumonia-like symptoms. This process is called primary infection and in most cases resolves by itself within 4 to 12 weeks, after which a latent state of TB develops. Nine out of 10 people with latent TB never experience subsequent disease and are not infectious to others. The only evidence of TB infection is a positive tuberculin skin test.
In 10% of infected individuals, the TB infection undergoes reactivation at some point, causing active TB disease. Progression to active disease and obvious symptoms (cough, weight loss, and fever) usually occurs within the first 2 years after infection but may occur at any time.
All people infected with HIV should be tested for TB and, if infected, begin complete therapy as soon as possible to prevent active TB disease. HIV-infected persons with either latent TB infection or active TB disease can be effectively treated. The first step is to ensure that HIV-infected persons are tested for TB. The second step is to help those infected with TB to get proper treatment and prevent rapid progression from latent TB infection to active TB disease.
The blood assay for TB testing, QuantiFERON-TB Gold (QFT-G), can be used in any situation in which a tuberculin skin test (TST) is used. It offers quicker results, one-step testing, and dependable accuracy. Results are available 24 hours after blood collection. However, laboratory analysis must begin within 12 hours of blood collection, necessitating rapid transport of specimens. The CDC (2007c) cautions that there are limited data on the use of QFT-G in children under age 17 and in immunocompromised persons, such as people with HIV/AIDS.
A diagnosis of latent tuberculosis infection (LTBI) requires that TB disease be excluded by medical evaluation, which should include evaluating signs and symptoms associated with TB disease, a chest x-ray, and, when indicated, examination of sputum or other clinical samples for the presence of M. tuberculosis.
Treatment of HIV/TB coinfected patients involves a complex 6- or 9-month multidrug regimen. All these drugs have significant side effects, which can lead to nonadherence and development of MDR TB, which is much more difficult to treat successfully. Coinfected individuals are at increased risk of developing active TB disease, and their anti-HIV medications must be carefully orchestrated to coincide with the TB regimen. Ideally, this complex care involves experts in the management of both tuberculosis and HIV disease (CDC, 2007).
Hepatitis is inflammation of the liver that may be caused by drugs and toxic agents or by one of several viruses, including hepatitis A, B, C, D, and others. People who are HIV-positive are at risk for hepatitis A, B, and C infection. Hepatitis A is transmitted by fecal/oral route, usually by contamination of water or food due to poor sanitation. Hepatitis B (HBV) and C (HCV) are transmitted by the blood and body fluids of an infected person.
HIV-infected people should be tested for both A and B viruses, and if they test negative, should receive vaccines against both. However, there is no vaccine for HCV.
Those who receive hepatitis B vaccine should be tested for antibodies to hepatitis B surface antigen (antiHBs) 1 to 2 months after completion of the primary series of hepatitis B vaccine. Those who fail to respond should be revaccinated with up to three additional doses.
|Source: Washington State Department of Health, 2007.|
(more likely if blood present)
(more likely if blood present)
(but may be transmitted if blood is present)
(but may be transmitted if blood is present)
|Target in the body||Immune System||Liver||Liver|
|Risk of infection after needlestick exposure to infected blood||0.5%||1–31%||2–3%|
Hepatitis B (HBV) can cause chronic liver disease or liver cancer, which makes vaccination essential to prevention. HBV vaccine is relatively inexpensive for infants and children and commonly administered to most infants before their first birthday. It is critical that infants whose mothers are HBV positive receive the vaccine; otherwise, they have a 90% chance of developing the disease. Adult doses of HBV vaccine cost about $150 per person, which may explain why most adults are not vaccinated against HBV.
Symptoms of HBV may vary. Some people may feel fine and look healthy; others may have only mild symptoms, such as loss of appetite, extreme fatigue, abdominal pain, jaundice (yellowing of the eyes and skin), joint pain, malaise, dark urine, nausea or vomiting, and skin rashes. Still others may experience more severe symptoms and may be incapacitated for weeks or months. Long-term complications may also occur, including chronic hepatitis, recurring liver disease, liver failure, or cirrhosis (chronic liver damage).
Risk factors for HBV include:
There are no medications available for recently acquired (acute) HBV infection. There are antiviral drugs available for the treatment of chronic HBV infection, but they are not always effective.
Hepatitis C (HCV) is the most common chronic bloodborne infection in the United States and a leading cause of chronic liver disease. HCV was discovered in the late 1980s, although it was probably being spread for decades prior to that. The CDC (2009) estimates that 3.2 million Americans have been infected with HCV, many of them from blood transfusions, and half of them do not know they are HCV-positive. (Since 1992, all blood donations in the United States have been tested for HCV.) People infected with HCV may have no symptoms for decades. When symptoms do appear, they are similar to those of HBV (see above).
An estimated one third of HIV-positive people in the United States are also infected with HCV. Incidence is even higher among HIV-positive injection drug users (IDUs) (50%–90%). Coinfection with HIV and HCV is associated with higher titers of HCV, more rapid progression to HCV-related liver disease, and increased risk for cirrhosis of the liver.
Liver disease from chronic HCV is now one of the leading causes of death among people living with HIV. Individuals coinfected with HIV and HCV should restrict alcohol consumption and if possible avoid alcohol altogether because of potential liver damage.
The U.S. Public Health Service/Infectious Disease Society of America guidelines recommend that all HIV-infected persons be screened for HCV infection.
Coinfected patients also need to consult their health professional before taking any new medications, including over-the-counter (OTC), alternative/complementary, or herbal medicines, because of their possible effects on the liver. Those receiving ART may also be at risk for drug-induced liver injury (DILI) and should be carefully monitored.
In coinfected patients with lower CD4 counts (<200 cell/mm3), it may be preferable to initiate antiretroviral therapy and delay HCV therapy until CD4 counts increase. Patients receiving or considering therapy with ribavirin should avoid didanosine, stavudine, and zidovudine. Antiretroviral agents with the greatest risk of DILI should be used with caution (Public Health Service Task Force, 2009).
Although there is no cure for HIV infection, there are treatment options that can help people living with HIV experience long and productive lives. Antiretroviral therapy (ART) for the treatment of HIV infection has improved steadily since the advent of potent combination therapy in 1996. New drugs have been approved that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability.
Because the science evolves rapidly, therapeutic options and preferences are continually changing. Treatment guidelines are updated frequently and are available on the AIDSinfo website at http://www.aidsinfo.nih.gov.
Act Against AIDS
AIDS Education Global Information System (AEGIS)
AIDSinfo (Comprehensive site of the USDHHS)
The Body HIV/AIDS Information
Centers for Disease Control and Prevention (CDC)
CDC National Prevention Information Network
CDC STD and AIDS Hotlines
English: 800-342-2437 or 800-227-8922
HIV InSite, University of California San Francisco
Centers for Disease Control and Prevention (CDC). (2009). Disease burden from viral hepatitis A, B, and C in the United States. Retrieved September 10, 2010, from http://www.cdc.gov/hepatitis/PDFs/disease_burden.pdf.
Centers for Disease Control and Prevention (CDC). (2007). Managing drug interactions in the treatment of HIV-related tuberculosis. Retrieved April 9, 2008, from http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm.
Feldman JG, Minkoff H, Schneider MF, Gange SJ, et al. (2006). Association of cigarette smoking with HIV prognosis among women in the HAART era: A report from the women’s interagency HIV study. American Journal of Public Health, 96, 1060–65.
Hoberg MA, Aberg JA, Cheever LW, et al. (2010). Development of national and multiagency HIV care quality measures. Clinical Infectious Diseases, 51(6), 732–738.
McNaghten AD, Hanson DL, Dworkin MS, & Jones JL. (2004). Differences in prescription of antiretroviral therapy in a large cohort of HIV-infected patients. Journal of Acquired Immune Deficiency Syndrome, 32(5), 499–505.
McNeil DG Jr. (2003). Africans outdo Americans in following AIDS therapy. New York Times, September 3, 2003.
Office of Women’s Health. (2009). Women and HIV/AIDS: Treatment. U.S. Department of Health and Human Services. Retrieved January 20, 2010, from http://www.womenshealth.gov/hiv/treatment.
Panel on Antiretroviral Guidelines for Adults and Adolescents, (2009). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, December 1, 2009; 1-161. Retrieved November 28, 2010, from http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission in the United States. (2010). Recommendations for the use of antiretroviral drugs in pregnant HIV1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. May 24, 2010. Retrieved September 30, 2010, from http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf.
Public Health Service Task Force. (2009). Recommendations for the use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. Retrieved January 12, 2010, from http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf.
Ray W, Murray K, Meredith S, et al. (2004). Oral erythromycin and the risk of sudden death from cardiac causes. New England Journal of Medicine, 351, 1089–96.
Smith RJ, Okano JT, Kahn JS, Bodine EN, & Blower S. (2010). Evolutionary dynamics of complex networks of HIV drug-resistant strains: The case of San Francisco. Science, 327(5966), 697–701.
Washington State Department of Health. (2007). KNOW: HIV Prevention Education, 2007, Revised Edition 6: An HIV and AIDS Curriculum Manual for Healthcare Facility Employees. Olympia: Author.
Zolopa AR & Katz MH. (2010). HIV infection and AIDS. In SJ McPhee and MA Papadakis, Current Medical Diagnosis and Treatment 2010 (49th ed.). New York: McGraw-Hill Medical.
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