18: AIDS, HIV Infection, and Related Conditions

Chapter 18

AIDS, HIV Infection, and Related Conditions

On June 5, 1981, when the Centers for Disease Control (CDC) reported five cases of Pneumocystis carinii (now jiroveci) pneumonia in young homosexual men in Los Angeles, few suspected that it heralded a pandemic of acquired immunodeficiency syndrome (AIDS). In 1983, a retrovirus (later named the human immunodeficiency virus [HIV]) was isolated from a patient with AIDS. Since that first report, more than 70 million persons have been infected with HIV, and more than 30 million have died of AIDS.< ?xml:namespace prefix = "mbp" />1 The total number of deaths has exceeded those caused by the Black Death of 14th-century Europe and the influenza pandemic of 1918 and 1919. About 95% of HIV-infected persons live in low- to middle-income regions, countries, and in sub-Saharan Africa. More than 40% of new infections (excluding those in infants) occur in young people 15 to 24 years of age.2,3

AIDS is an infectious disease that is transmitted predominantly through intimate sexual contact and by parenteral means. In view of the nature of this bloodborne pathogen, HIV infection and AIDS have important implications for dental practitioners. Although HIV has rarely been transmitted from patients to health care workers, this may occur, and the patient with HIV infection or AIDS may be medically compromised and may need special dental management considerations. On the basis of current statistics, the average dental practice is predicted to encounter at least two patients infected with HIV per year.

Definition

The definition of AIDS provided by the CDC has been revised several times over the years, and in 2008 it was revised to be laboratory-confirmed evidence of HIV infection in a person who has stage 3 HIV infection (i.e., a CD4+ lymphocyte count less than 200 cells/µL).4 This definition also includes HIV-infected persons whose CD4+ count may be above 200 but have an AIDS-defining condition, as shown in Box 18-1. Of note, because of the provision of antiretroviral drug regimens, not all patients progress to AIDS or develop life-threatening opportunistic infections.5,6

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Box 18-1 AIDS-Defining Conditions

Bacterial infections, multiple or recurrent*

Candidiasis of bronchi, trachea, or lungs

Candidiasis of esophagus

Cervical cancer, invasive§

Coccidioidomycosis, disseminated or extrapulmonary

Cryptococcosis, extrapulmonary

Cryptosporidiosis, chronic intestinal (longer than 1 month in duration)

Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month

Cytomegalovirus retinitis (with loss of vision)

Encephalopathy, HIV-related

Herpes simplex: chronic ulcers (>1 month’s duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)

Histoplasmosis, disseminated or extrapulmonary

Isosporiasis, chronic intestinal (>1 month’s duration)

Kaposi sarcoma

Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex*

Lymphoma, Burkitt (or equivalent term)

Lymphoma, immunoblastic (or equivalent term)

Lymphoma, primary, of brain

Mycobacterium avium complex or Mycobacterium kansasii infection, disseminated or extrapulmonary

Mycobacterium tuberculosis infection of any site, pulmonary,§ disseminated, or extrapulmonary

Mycobacterium infection, other species or unidentified species, disseminated or extrapulmonary

Pneumocystis jiroveci pneumonia

Pneumonia, recurrent§

Progressive multifocal leukoencephalopathy

Salmonella septicemia, recurrent

Toxoplasmosis of brain, onset at age >1 month

Wasting syndrome attributed to HIV

AIDS, Acquired immunodeficiency syndrome.

* Only among children younger than 13 years of age. (Data from Centers for Disease Control and Prevention [CDC]: 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age, MMWR Recomm Rep 43:1, 1994; Centers for Disease Control and Prevention [CDC]: 2008 revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years—United States, MMWR Recomm Rep 57:9, 2008.)

Condition that might be diagnosed presumptively.

§Only among adults and adolescents 13 years of age and older. (Data from Centers for Disease Control and Prevention [CDC]: 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults, MMWR Recomm Rep 41: 1, 1993.)

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Incidence and Prevalence

An estimated 2.7 million people across the globe are newly infected with HIV annually. At the end of 2009, there were an estimated 33.4 million persons globally and an estimated 1.1 million persons in the United States who were infected and living with HIV infection/AIDS.1 Worldwide, these rates represent a 3-fold higher prevalence since 1990, but a decline since the peak prevalence that occurred in 1999. In the United States, approximately 24% are undiagnosed and unaware of their infection, 42% are HIV-positive but not yet progressed to AIDS, and 34% have AIDS.7

The CDC estimated that approximately 56,300 persons were newly infected with HIV in 2006 and 42,000 were newly infected in 2009.7,8 A majority of those infected are between the ages of 20 and 45, male, and disproportionately black. Recent estimates for cases of HIV infection diagnosed in the United States by age, race, and transmission category are shown in Table 18-1.9 The overall prevalence (among persons older than 13 years of age) is 70.8 for black men who have sex with men (MSM) and 14.6 for white MSM per 100,000,10 and the number of cases of HIV infection due to heterosexual transmission remains greater than 15,000 per year.11

TABLE 18-1 Select Patient Characteristics in HIV Infection and AIDS*

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The estimated number of AIDS diagnoses in the United States for 2009 was approximately 34,000. Adult and adolescent AIDS accounted for about 99% of the cases, 75% of which occurred in males and 25% in females. The cumulative estimated number of AIDS diagnoses through 2009 in the United States was 1.1 million.7,11

Since the introduction of protease inhibitors in 1996 and the advent of highly active antiretroviral therapy (HAART), the epidemic of AIDS in the United States has slowed and stabilized. Still, the CDC reports approximately 2250 new cases per month. As of the end of 2006, 565,927 deaths have been reported in the United States due to AIDS, and 14,627 deaths occurred in 2006 alone. Most deaths occur in adults, with few deaths reported in children younger than age 13 in 2006.12 In the United States, AIDS is the leading cause of death in men 25 to 44 years of age. Worldwide, there are 2 million deaths per year, and more than 30 million persons have died of AIDS.13 AIDS is the world’s leading cause of death in women and men aged 15 to 59 years.2,13

Several trends in the epidemiology of AIDS have emerged over the decades. In the United States, peak incidence was in 1993 and peak incidence of death was 50,877 in 1995. The past 2 decades witnessed a decline in the number of cases of AIDS associated with blood and blood products in transfusion and hemophiliac patient groups, specifically attributable to improved testing (starting in 1985) of donor blood for HIV antibodies and the heating of factor VIII replacement preparations. Also, an increase in the ratio of infected women to men occurred a decade ago; this ratio has remained stable in about 25% of women but is particularly higher in the 30- to 40-year age group of black women.11

At present there is no effective vaccine to prevent HIV infection, although large research efforts have and continue to be made in this arena. Also, a nonpandemic relating strain of HIV, known as HIV-2, occurs less commonly throughout the world. Most cases of HIV-2 infection have occurred in West Africa, with a limited number of cases occurring in Canada and the United States. Most persons infected with HIV-2 are long-term nonprogressors because viral loads generally are low, and the immunosuppression is not as severe.14,15

Etiology

AIDS is caused by HIV, a nontransforming retrovirus of the lentivirus family. There are two HIV subtypes, HIV-1 and HIV-2, and many strains of each. HIV-1 was first identified in 1983 by Francoise Barre-Sinoussi in the lab of Luc Montaignier of the Pasteur Institute. They first called it lymphadenopathy-associated virus. Within a year of this discovery, a team led by Robert Gallo from the National Institutes of Health isolated a retrovirus identified as the human T lymphotropic virus III (HTLV-III) and labeled it as the etiologic agent for AIDS. In 1984, Jay Levy’s team in San Francisco also isolated a retrovirus, AIDS-related virus (ARV), and designated it as the causative agent for AIDS. All three viruses were similar retroviruses, but minor differences were observed in their amino acid sequences. Variation in disease patterns are attributed to the slight sequence differences among HIV strains, which also makes difficult the production of a vaccine. The three groups essentially were describing the same retrovirus, which can change its antigenicity. Until 1986, most workers in the field referred to the virus as HTLV-III and considered it to be the causative agent for AIDS. In 1986, the World Health Organization (WHO) recommended that the AIDS virus be called the human immunodeficiency virus1618 (Figure 18-1). Subsequent analysis of frozen tissue and serum samples from select patients who died of uncertain causes in the 1950s and 1960s demonstrated that HIV had infected these patients, indicating its presence in humans for more than 60 years.19

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FIGURE 18-1 The structure of human immunodeficiency virus, showing the p24 capsid protein surrounding two strands of viral RNA.

(From Copstead LC, Banasik JL: Pathophysiology, ed 4, St. Louis, 2010, Saunders.)

HIV is an enveloped RNA retrovirus about 100 nM in diameter. Glycoproteins (gp41 and gp120) stud the surface of the envelope and serve to bind to human cells (Figure 18-2). Internal to the envelope is a protein capsid (p24) that surrounds essential viral enzymes (protease, integrase, reverse transcriptase) and an RNA inner core. It infects most human cells. However, the cells most commonly infected are those with CD4+ receptors, including T helper lymphocytes (CD4+ cells) and macrophages. Accordingly, these cells are most deeply involved in HIV infection. Additional coreceptors that allow HIV to infect human cells include CCR5, CXCR4 (fusin), and CCR2.20

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FIGURE 18-2 Life Cycle of the Human Immunodeficiency Virus.

(From Copstead LC, Banasik JL: Pathophysiology, ed 4, St. Louis, 2010, Saunders.)

HIV-1 infection is divided into stages: entry, reverse transcription of RNA to DNA, export of the viral DNA from the cytoplasm to the nucleus and integration into the host chromosome, transcription, translation and cleavage of the polyproteins produced, assembly of virions, and budding of virions. The process is largely regulated by the proteins tat, rev, and nef, which are necessary for viral replication. Virulence has been mapped to the carboxyl-terminal half of the gp120, which has been referred to as the V3 loop.20 (For additional information see Chapter 182 in Fauci AS, et al., (editors): Harrison’s Principles of Internal Medicine, ed 17, New York, 2008, McGraw Medical.)

Pathophysiology and Complications

Transmission of HIV is by exchange of infected bodily fluids from sexual contact and through blood and blood products. The most common method of sexual transmission in the United States is anal intercourse in MSM, in whom the risk of HIV infection is 40 times higher than in other men and in women.21 Heterosexual transmission (male to female or female to male) is the second most common form of transmission in the United States but accounts for 80% of the world’s HIV infections. Heterosexual transmission of HIV can occur through sexual contact of carriers who are heterosexual injection drug users, bisexual men, or blood recipients of either gender. Transmission from injection drug use is the third largest group to be affected in the United States.22

The virus is found in blood, seminal fluid, vaginal secretions, tears, breast milk, cerebrospinal fluid, amniotic fluid, and urine. Blood, semen, breast milk, and vaginal secretions are the main fluids that have been shown to be associated with transmission of the virus.

Vertical transmission to infants born of infected mothers can occur at birth or transplacentally. HIV has been found in saliva, and transmission by transfer of saliva possibly contaminated with blood has been reported from providing premasticated food from HIV-infected parents to infants.23 Casual contact has not been demonstrated as a means of transmission. Inflammation and breaks in the skin or mucosa (e.g., presence of other sexually transmitted diseases) and high concentrations of HIV in bodily fluids increase the risk of transmission.2426 Oral sex is an inefficient but documented mode of transmission.27 The risk of transmission from a blood transfusion is estimated to be less than 1 in 1 million because of current screening measures. Occupational exposure also is a source of transmission and health care provider to patient transmission has occurred (see later under “Dental Management”).

Once HIV has gained access to the bloodstream, the virus selectively seeks out T lymphocytes (specifically T4 or T helper lymphocytes) (see Figure 18-2). The virus binds to the CD4+ lymphocyte cell surface specifically through the highly glycosylated outer surface envelope (gp120) proteins. Upon infection, reverse transcriptase catalyzes the synthesis of a haploid, double-stranded DNA provirus, which becomes incorporated into the chromosomal DNA of the host cell. Thus integrated, the provirus genetic material may remain latent in an unexpressed form until events occur that activate it, at which time DNA transcription rapidly occurs and new virions are produced. The virus is lymphotropic; hence, the cells it selects for replication are soon destroyed. Once the virus takes hold, it causes a reduction in the total number of T helper cells, and a marked shift in the ratio of CD4+ to CD8+ lymphocytes occurs. The normal ratio of T helper to T suppressor lymphocytes is about 2 : 1 (60% T helper, 30% T suppressor). In AIDS, the T4/T8 ratio is reversed. This marked reduction in T helper lymphocytes, to a great degree, explains the lack of an effective immune response seen in patients with AIDS and contributes to the increase in malignant disease that has been found to be associated with AIDS, including Kaposi sarcoma, lymphoma, carcinoma of the cervix, and carcinoma of the rectum.20

Table 18-2 presents the clinical stages of HIV infection through frank AIDS. More than 50% of persons exposed to the virus develop an acute and brief viremia (seroconversion sickness) within 2 to 6 weeks of HIV exposure and then develop antibodies (anti-gag, anti-gp120, anti-p24) between weeks 6 and 12. A few may take 6 months or longer to achieve seroconversion. A concomitant, transient fall in CD4+ cells occurs (lymphopenia, along with high titers of plasma HIV), but patients do not develop evidence of immunosuppression. Various flulike symptoms occur during this acute infection, which usually lasts about 2 to 4 weeks. Only an estimated 20% of affected persons seek medical attention. During primary infection, HIV disseminates throughout the lymphoid tissue, incubates and replicates. These events allow HIV to establish a chronic infection and reservoirs of latently infected cells.

TABLE 18-2 Features of HIV Infection and Disease Progression

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As time progresses, a steady-state viremia develops, and several thousand copies of HIV are present in the blood (Figure 18-3). This clinical latency period is characterized by evolution of the virus within its host to generate closely related, yet distinct mutant viruses that serve to evade the surveying immune response and circulating antibodies. Although the infection is clinically latent, there is a progressive decline in immune function evident as progressive depletion of CD4+ lymphocytes with ultimate pancytopenia, impaired lymphocyte proliferation, and cytokine responses to mitogens and antigens; impaired cytotoxic lymphocyte function and natural killer cell activity; anergy to skin testing; and diminished antibody responses to new antigens.20

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FIGURE 18-3 The natural history of human immunodeficiency virus infection.

(From Brookmeyer R, Gail MH: AIDS epidemiology: a quantitative approach, New York, 1994, Oxford University Press.)

In untreated persons and in persons in whom therapy is ineffective, the CD4+ count continues to decline while HIV proliferates. As the CD4+ count drops and approaches 200 cells/µL, persons can exhibit weight loss, diarrhea, and night sweats (see Figure 18-3). When the CD4+ count drops to below 200 cells/µL, the person has AIDS and is susceptible to opportunistic infections, including Pneumocystis pneumonia, toxoplasmosis, cryptococcosis, influenza, histoplasmosis, tuberculosis, cytomegalovirus (CMV) infection, mucocutaneous diseases such as candidiasis, and neoplasms previously discussed. Neurologic disease is common and includes secondary opportunistic infections as well as primary HIV infection of macrophages, neurons, and microglial cells in the CNS that leads to rapidly progressive dementia.

Evidence suggests that persons most susceptible to developing AIDS are those with repeated exposure to the virus who also have an immune system that has been challenged by repeated exposure to various antigens (semen, hepatitis B, or blood products).20 The median time from primary infection to the development of AIDS in untreated patients is about 10 years. About 30% of patients with AIDS can be expected to live approximately 2 to 3 years, with most others living 10 years or longer. Long-term survival with HIV infection (beyond 15 years) occurs and is associated with less virulent HIV strains, lower-level viremia, HAART, and robust immune responses.28

Clinical Presentation

Signs and Symptoms

During the first 2 to 6 weeks after initial infection with HIV, more than 50% of patients develop an acute flulike syndrome marked by viremia that may last 10 to 14 days. Others may not manifest this symptom complex. Symptomatic persons often develop lymphadenopathy, fever, pharyngitis and a skin rash but generally do not display circulation antibodies until the 6th week to 6th month. The severity of the initial acute infection with HIV (i.e., level of viremia) is predictive of the course the infection will follow. In one study, 78% of persons with a long-lasting acute illness developed AIDS within 3 years; by contrast, only 10% of those patients with no acute illness at seroconversion developed AIDS within 3 years.29

The CDC defines three stages of HIV infection.4 Box 18-2 illustrates the definitions for each stage. Briefly, stage 1 generally begins immediately after HIV exposure and may last for years. Affected persons are HIV antibody–positive but are asymptomatic and show no other laboratory abnormalities. Stage 2 is characterized by progressive immunosuppression and symptomatic disease. Patients who demonstrate various laboratory changes (i.e., lymphopenia: T helper/T suppressor ratio usually less than 1) in addition to HIV antibody positivity also may show clinical signs or symptoms, such as enlarged lymph nodes, night sweats, weight loss, oral candidiasis, fever, malaise, and diarrhea. Persons in stage 3 have AIDS and can demonstrate a variety of immunesuppression-related diseases. Opportunistic infections predominate as the CD4+ T count approximates 200 cells/µL; then malignancies, wasting syndrome, and a progressive form of dementia can develop. Patients may become confused and disoriented or may experience short-term memory deficits. Others develop severe depression or paranoia and show suicidal tendencies. Figure 18-3 depicts the natural history of HIV, and Table 18-2 lists the diseases associated with the progression of HIV infection through frank AIDS.

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Box 18-2 CDC Staging of HIV Infection in Adults and Adolescents

Stage 1: Laboratory confirmation of HIV infection, no AIDS-defining conditions and CD4+ T lymphocyte count of ≥500 cells/µL or CD4+ T lymphocyte percentage of total lymphocytes of ≥29.

Stage 2: Laboratory confirmation of HIV infection, no AIDS-defining condition, and laboratory confirmation of HIV infection and CD4+ T lymphocyte count of 200-499 cells/µL or CD4+ T lymphocyte percentage of total lymphocytes of 14-28.

Stage 3 (AIDS): Laboratory confirmation of HIV infection and CD4+ T lymphocyte count is <200 cells/µL or CD4+ T lymphocyte percentage of total lymphocytes is <14 or documentation of an AIDS-defining condition (see Box 18-1). Documentation of an AIDS-defining condition supersedes a CD4+ T lymphocyte count of ≥200 cells/µL and a CD4+ T lymphocyte percentage of total lymphocytes of ≥14.

CDC, Centers for Disease Control and Prevention; HIV, Human immunodeficiency virus; AIDS, Acquired immunodeficiency syndrome.

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Laboratory Findings

Most patients exposed to the virus, with or without clinical evidence of disease, show antibodies to the virus by the 6th month of infection. Patients with advanced HIV infection or AIDS have an altered ratio of CD4+/CD8+ lymphocytes, a decrease in total number of lymphocytes, thrombocytopenia, anemia, a slight alteration in the humoral antibody system, and a decreased ability to show delayed allergic reactions to skin testing (cutaneous anergy).20 CD4+ and CD8+ cell counts should be performed at the time of HIV diagnosis and then every 3 to 4 months.2

The enzyme-linked immunosorbent assay (ELISA) is the screening test for identification of antibodies to HIV. It is 90% sensitive but has a high rate of false-positive results. Current practice is to screen first with ELISA. If the results are positive, a second ELISA is performed. All positive results are then confirmed with Western blot analysis. This combination of tests is accurate more than 99% of the time. Positive ELISA and Western blot test results indicate only that the individual has been exposed to the AIDS virus. If results of the Western blot are indeterminate, HIV infection is rarely, if ever, present. These tests, however, do not indicate the status of the HIV infection or whether AIDS is present. However, patients with positive results on the ELISA and Western blot test are considered potentially infectious. ELISA testing for HIV in saliva is an alternative approach that is 98% sensitive in detecting antibodies to HIV.30 More recently, Abbott has developed a combination assay, the ARCHITECT HIV Ag/Ab Combo assay (Abbott Laboratories, Abbott Park, Illinois), that can simultaneously detect the combined presence of HIV antigens (the p24 antigen produced by HIV) and antibodies to HIV. This recently FDA approved test is expected to be important for diagnosing HIV infection in the acute phase of the disease when antibodies are not yet present and for ongoing monitorin/>

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Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 18: AIDS, HIV Infection, and Related Conditions
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