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Pulmonary Infections in Patients with Human Immunodeficiency Virus Disease
Section 5
INFECTIOUS DISEASES
Chapter 29
Pulmonary Infections in Patients with Human Immunodeficiency Virus Disease Robert F. Miller l Marc C.I. Lipman l Alison Morris
EPIDEMIOLOGY, RISK FACTORS, AND PATHOPHYSIOLOGY HUMAN IMMUNODEFICIENCY VIRUS INFECTION: BACKGROUND
It is now more than 30 years since the first report from Los Angeles, in the United States, of an “outbreak” of Pneumocystis pneumonia (PCP) among homosexual men that heralded the onset of the global human immunodeficiency virus (HIV) pandemic. Since the early 1980s, HIV infection has steadily spread throughout the world and caused an estimated 25 million deaths. At the end of 2009, according to the United Nations Program on HIV/AIDS (UNAIDS), 33.3 million people worldwide were HIV-infected, a majority of these living in resourcepoor countries. In 2008, the Centers for Disease Control and Prevention (CDC) reported that in the United States, 1,178,350 persons 13 years of age or older were living with HIV infection, and more than 40,000 were newly infected each year. In the United Kingdom, the Health Protection Agency estimated that in 2009, 86,500 persons were living with HIV infection and 6630 were newly diagnosed. Over the previous 10 years, the proportion of U.K. residents older than 50 years of age who were living with HIV infection had increased from 1 in 20 to 1 in 5. Current antiretroviral therapy (ART) regimens have the potential to suppress HIV replication for decades. In 2011, persons with newly diagnosed HIV infection living in nations such as the United States and the United Kingdom that provide access to treatment and care have an expectation that on ART their life expectancy will approach that for an age-matched HIV-uninfected population. Their clinicians now manage HIVinfected populations whose medical complications reflect agerelated comorbidity. Unfortunately, these observations do not apply to a majority of people worldwide with HIV infection, who live in financially impoverished environments with little access to comprehensive health care prevention and treatment programs. Respiratory disease remains an important contributor to morbidity and mortality, and more than two thirds of HIVinfected persons have at least one respiratory episode during the course of their illness. With relatively preserved immune responses, infectious agents are similar to those seen in the general population, although at a higher frequency. With progressive HIV disease, subjects are at an increased risk for opportunistic disease. For example, the North American Prospective Study of Pulmonary Complications of HIV Infection (PCHIS), a multicenter cohort drawn from all HIV risk groups at various 346
stages of immunocompromise, revealed that over an 18-month study period, of approximately 1000 subjects who were not using ART, 33% reported an upper respiratory tract infection, 16% had an episode of acute bronchitis, 5% acute sinusitis, 5% bacterial pneumonia, and 4% developed PCP. The immune dysregulation that arises from HIV infection means that bacteria, mycobacteria, fungi, viruses, and protozoa can all cause disease in patients with advanced infection. Box 29-1 shows the organisms that typically infect the lung in HIV disease. Of these, the agents of bacterial infections, tuberculosis, and PCP are the most important. In the West, 40% of diagnosed AIDS cases are due to PCP. This chapter provides a brief general overview of the epidemiology and pathogenesis of HIV infection, followed by a more detailed discussion of other important aspects of the disease and its infectious pulmonary complications. It is reported that by the end of 2009, 33.3 million people worldwide had acquired HIV infection (Figure 29-1). Of these, over 40% are thought to have developed AIDS (for definition of AIDS, see Tables 29-1 and 29-2 and Box 29-2). Globally, 2.6 million people acquired HIV infection in 2009, and 1.8 million died of AIDS. The developing world has been most affected. Sub-Saharan Africa is the current epicenter of the pandemic (accounting for two thirds of all infections); here, nearly 6% of adults are HIV-infected. South and Southeast Asia are responsible for almost a fifth of the estimated HIV global burden. In Central-Eastern Europe and Central Asia, there are currently 1.4 million HIV-infected persons. In the developed world, North America and Western Europe account for approximately 1.5 million and 820,000 infections, respectively. The vast majority of these are spread through sexual contact, although vertical (mother-to-child) and blood-borne infections are common. In the developing world, heterosexual transmission is the norm. In North America and Europe, men who have sex with men constitute the largest group of HIVinfected persons. VIROLOGY AND IMMUNOLOGY OF THE HUMAN IMMUNODEFICIENCY VIRUS
HIV was first isolated in 1983 from patients with symptoms and signs of immune compromise. Two subtypes, HIV-1 and HIV-2, have subsequently been identified. HIV-1 (hereafter referred to as HIV) is responsible for a majority of infections, is associated with a more aggressive clinical course, and is the focus of this chapter.
INFECTIOUS DISEASES
Chapter 29
Pulmonary Infections in Patients with Human Immunodeficiency Virus Disease Robert F. Miller l Marc C.I. Lipman l Alison Morris
EPIDEMIOLOGY, RISK FACTORS, AND PATHOPHYSIOLOGY HUMAN IMMUNODEFICIENCY VIRUS INFECTION: BACKGROUND
It is now more than 30 years since the first report from Los Angeles, in the United States, of an “outbreak” of Pneumocystis pneumonia (PCP) among homosexual men that heralded the onset of the global human immunodeficiency virus (HIV) pandemic. Since the early 1980s, HIV infection has steadily spread throughout the world and caused an estimated 25 million deaths. At the end of 2009, according to the United Nations Program on HIV/AIDS (UNAIDS), 33.3 million people worldwide were HIV-infected, a majority of these living in resourcepoor countries. In 2008, the Centers for Disease Control and Prevention (CDC) reported that in the United States, 1,178,350 persons 13 years of age or older were living with HIV infection, and more than 40,000 were newly infected each year. In the United Kingdom, the Health Protection Agency estimated that in 2009, 86,500 persons were living with HIV infection and 6630 were newly diagnosed. Over the previous 10 years, the proportion of U.K. residents older than 50 years of age who were living with HIV infection had increased from 1 in 20 to 1 in 5. Current antiretroviral therapy (ART) regimens have the potential to suppress HIV replication for decades. In 2011, persons with newly diagnosed HIV infection living in nations such as the United States and the United Kingdom that provide access to treatment and care have an expectation that on ART their life expectancy will approach that for an age-matched HIV-uninfected population. Their clinicians now manage HIVinfected populations whose medical complications reflect agerelated comorbidity. Unfortunately, these observations do not apply to a majority of people worldwide with HIV infection, who live in financially impoverished environments with little access to comprehensive health care prevention and treatment programs. Respiratory disease remains an important contributor to morbidity and mortality, and more than two thirds of HIVinfected persons have at least one respiratory episode during the course of their illness. With relatively preserved immune responses, infectious agents are similar to those seen in the general population, although at a higher frequency. With progressive HIV disease, subjects are at an increased risk for opportunistic disease. For example, the North American Prospective Study of Pulmonary Complications of HIV Infection (PCHIS), a multicenter cohort drawn from all HIV risk groups at various 346
stages of immunocompromise, revealed that over an 18-month study period, of approximately 1000 subjects who were not using ART, 33% reported an upper respiratory tract infection, 16% had an episode of acute bronchitis, 5% acute sinusitis, 5% bacterial pneumonia, and 4% developed PCP. The immune dysregulation that arises from HIV infection means that bacteria, mycobacteria, fungi, viruses, and protozoa can all cause disease in patients with advanced infection. Box 29-1 shows the organisms that typically infect the lung in HIV disease. Of these, the agents of bacterial infections, tuberculosis, and PCP are the most important. In the West, 40% of diagnosed AIDS cases are due to PCP. This chapter provides a brief general overview of the epidemiology and pathogenesis of HIV infection, followed by a more detailed discussion of other important aspects of the disease and its infectious pulmonary complications. It is reported that by the end of 2009, 33.3 million people worldwide had acquired HIV infection (Figure 29-1). Of these, over 40% are thought to have developed AIDS (for definition of AIDS, see Tables 29-1 and 29-2 and Box 29-2). Globally, 2.6 million people acquired HIV infection in 2009, and 1.8 million died of AIDS. The developing world has been most affected. Sub-Saharan Africa is the current epicenter of the pandemic (accounting for two thirds of all infections); here, nearly 6% of adults are HIV-infected. South and Southeast Asia are responsible for almost a fifth of the estimated HIV global burden. In Central-Eastern Europe and Central Asia, there are currently 1.4 million HIV-infected persons. In the developed world, North America and Western Europe account for approximately 1.5 million and 820,000 infections, respectively. The vast majority of these are spread through sexual contact, although vertical (mother-to-child) and blood-borne infections are common. In the developing world, heterosexual transmission is the norm. In North America and Europe, men who have sex with men constitute the largest group of HIVinfected persons. VIROLOGY AND IMMUNOLOGY OF THE HUMAN IMMUNODEFICIENCY VIRUS
HIV was first isolated in 1983 from patients with symptoms and signs of immune compromise. Two subtypes, HIV-1 and HIV-2, have subsequently been identified. HIV-1 (hereafter referred to as HIV) is responsible for a majority of infections, is associated with a more aggressive clinical course, and is the focus of this chapter.