| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Dr. O’Neil is the Director for Graduate Medical Education, National Naval Medical Center
Correspondence to: Kevin M. O’Neil, MD, FCCP, CAPT MC USN, Pulmonary Clinic, National Naval Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889-5600; e-mail: kmoneil{at}bethesda.med.navy.mil
No physician in the past 20 years is likely to have escaped the impact of HIV/AIDS infection on the practice of medicine. As we enter the third decade of the AIDS epidemic, the human toll is staggering. As of June 2001, almost 800,000 patients in the United States have developed AIDS. Over half of these have died, the overwhelming majority under age 45.1 Over 900,000 people are estimated to be living with HIV infection.2 Worldwide, the statistics are even more sobering. As of December 2001, there were more than 40 million people infected with HIV, most living in sub-Saharan Africa and Asia. Over 22 million people have died, including 3 million in 2001 alone.2 In parts of southern Africa, the prevalence of HIV infection in pregnant women exceeds 30%. HIV/AIDS has reduced life expectancy by one third in several sub-Saharan African countries, and it is now the fourth leading cause of death worldwide. Cases continue to accumulate, with an estimated 5 million new infections in 2001.2
The pulmonary complications of HIV infection are well documented and diverse, and they constitute a major cause of morbidity and mortality.3 4 5 Infection with HIV causes predictable immunologic changes in the lung. In addition to the loss of CD4+ T cells, a lymphocytic alveolitis with CD8+ T cells, activation of pulmonary macrophages, and increased production of cytokines can all be seen, leading to progressive impairment in both cell-mediated and humoral immunity.3 Respiratory complaints are frequent in patients who are HIV-positive.5 6 Spirometry, while typically normal in asymptomatic individuals, is affected by both bacterial pneumonia and opportunistic infection with Pneumocystis carinii. Permanent reductions in FEV1, FVC, FEV1/FVC, and diffusing capacity for carbon monoxide have been noted following incidences of pneumonia7 as well as dysfunction of small airways8 and an increased prevalence of bronchial hyperresponsiveness.6 The clinical implications vary with the degree of immunosuppression, ranging from an increased incidence of bronchitis and sinusitis, with CD4 counts above 500/µL, to P carinii pneumonia (PCP) and Kaposi sarcoma, with CD4 counts below 200/µL.5
Advances in our understanding of the immunologic impact of HIV on disease progression have led to improved care and incremental increases in survival. Prophylaxis for opportunistic infections, corticosteroids for P carinii pneumonia, and the development of antiretroviral therapies provided some initial successes in the battle against HIV/AIDS. The current era of antiretroviral therapy began in late 1995, with the introduction of highly active antiretroviral therapy (HAART). HAART, defined as a combination therapy with drug regimens including protease inhibitors, nucleoside reverse-transcriptase inhibitors, and/or nonnucleoside reverse-transcriptase inhibitors, has had a significant impact on viral load, CD4+ cell count, and HIV-related mortality. Studies in both adult9 and pediatric populations10 report 75% and 67% reductions, respectively, in the risk of death with HAART. Similar reductions in the incidence of both community-acquired pneumonia11 and opportunistic infections, including Mycobacterium tuberculosis, cytomegalovirus, and PCP, have all been recently reported with HAART.9 12 13
In this issue of CHEST (see page 878), Taggart and coworkers add to our understanding of the impact of HAART on pulmonary disease in HIV infected individuals. In a retrospective review of their experience using bronchoscopy in the treatment of patients positive for HIV and presenting with respiratory symptoms, Taggart et al confirmed what most of us in centers with large HIV-positive populations have noted in our clinical practices—bronchoscopies for HIV-related pulmonary disease have dropped precipitously since the institution of HAART. In their study, despite progressive increases in patients who were followed in-clinic, the rates of bronchoscopy fell slightly, from 13% at the start of the study in 1989 to 10% in the early 1990s, when rates stabilized. With the introduction of HAART in 1996, the rates fell again to 4%. This drop does not appear to be due to changes in practice patterns. The indications for bronchoscopy remained largely unchanged over the time period, with > 85% of procedures done to rule out opportunistic infection, and there was little change in diagnostic yield post-HAART. This decline mirrors those reported by Balfe and Mohsenifar14 in Los Angeles, and by Murri et al15 in Rome, who noted 59% and 69% declines, respectively, in HIV-related bronchoscopies in their respective institutions over similar time periods.
Translating these results to most centers in the United States would likely result in even fewer procedures, as the authors had a fairly low threshold for bronchoscopy. Almost one third of patients undergoing the procedure had normal chest radiographs. The author’s institution also used bronchoscopy and BAL as its principal means for diagnosing PCP, still the most commonly diagnosed opportunistic infection, even with HAART. This is unlike many centers in North America, which have increasingly relied on induced sputum with monoclonal antibody staining and now PCR technologies to diagnose PCP.16 Even further reductions in bronchoscopies could potentially have occurred with the use of other testing, such as high-resolution CT for symptomatic patients with normal chest radiographs17 or diagnostic algorithms employing measurements of the diffusing capacity of the lung for carbon monoxide.18
Does this mean that the debate over empiric therapy vs early bronchoscopy is moot? Unfortunately, no! As Taggart and his coworkers have noted, 25 to 40% of their patients requiring bronchoscopy were new to the health-care system. There remains a large reservoir of HIV-infected individuals either unaware or choosing to ignore their infection who will present late in the course of their illness. In addition, the cost of HAART, roughly $8,000/yr in my institution, puts it out of reach for the overwhelming majority of HIV-positive individuals. Pulmonologists will continue to see referrals for newly diagnosed and noncompliant patients as well as treatment failures.
Increasingly, we will also have to learn to consider and treat new diseases affecting HIV-positive patients. As noted by others, HAART is not without toxicity. Drug interactions are common, including potential problems with antituberculosis chemotherapy.3 Hyperlactatemia and lactic acidosis are increasingly recognized complications of nucleoside reverse- transcriptase inhibitor therapy.19 20 21 Immune reconstitution syndromes with paradoxical worsening of tuberculosis,22 cytomegalovirus,23 and P carinii24 infections associated with beginning HAART have all been reported. Reactivation of latent sarcoidosis25 and the development of a sarcoid-like illness with a CD4+ alveolitis26 27 28 have been seen with the initiation of HAART. Immune reconstitution and control of infectious complications have allowed hepatic and cardiac failure to emerge as leading causes of death in the HIV-positive population.13 29 Lung cancer30 and COPD31 may also soon become more common indications for pulmonary referrals in the HAART treated HIV-positive patient population.
As we proceed through this unfamiliar territory, many challenges lie ahead: dealing with and minimizing medication-related toxicities and interactions; recognizing and treating new disorders related to immune reconstitution; and, increasingly, treating the chronic albeit accelerated courses of many lung diseases previously not considered important for HIV-positive patients. The greatest and most pressing challenge remains, however, the overwhelming numbers of patients for whom nothing has changed and for whom effective antiretroviral therapy is neither affordable nor accessible.
Footnotes
The opinions expressed represent the private personal views of the author and do not necessarily represent the views of the Department of the Navy or the Department of Defense.
References
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
