Profilaxis contra enfermedades oportunistas

The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Review Article

Drug Therapy
A L A S T A I R J . J . W O O D , M. D. , Editor

AGAINST O PPORTUNISTIC I NFECTIONS IN P ATIENTS WITH H UMAN I MMUNODEFICIENCY V IRUS I NFECTION JOSEPH A. KOVACS, M.D.,
AND

P ROPHYLAXIS

HENRY MASUR, M.D.

S

OON after the acquired immunodeficiency syndrome (AIDS) was first described in 1981,1-4 itbecame clear that opportunistic infections occurred with remarkable frequency and caused substantial morbidity and mortality among patients with AIDS. On the basis of a series of clinical trials, chemoprophylaxis to prevent initial episodes of certain opportunistic infections (primary prophylaxis) and subsequent episodes (secondary prophylaxis) became the standard of care. The success of highlyactive antiretroviral therapy (defined as combination antiretroviral regimens that include either a potent viral-protease inhibitor or a nonnucleoside reverse-transcriptase inhibitor) in reducing the incidence of AIDS-related opportunistic infections and consequent morbidity and mortality has led to a reassessment of the role of prophylaxis against these infections in patients with humanimmunodeficiency virus (HIV) infection who have durable antiviral responses.5-8 The Public Health Service and the Infectious Diseases Society of America have recently published revised guidelines for the prevention of opportunistic infections in patients with HIV infection.9 In this review we provide a perspective on these guidelines and on the principles and recent developments that we think should formthe basis for modifications in the approach to the prevention of both initial episodes and recurrences or relapses of these infections.
CURRENT EPIDEMIOLOGY OF OPPORTUNISTIC INFECTIONS

Reports from individual institutions as well as large, multicenter studies have documented dramatic deFrom the Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Md.Address reprint requests to Dr. Masur at the National Institutes of Health, Clinical Center, Critical Care Medicine Department, 10 Center Dr., Bethesda, MD 20892-1662, or at hmasur@nih.gov. ©2000, Massachusetts Medical Society.

creases in the occurrence of opportunistic infections since the introduction of combination antiretroviral regimens, especially regimens that include HIV-proteaseinhibitors.5-8 The declining incidence of virtually all opportunistic infections is highlighted by a recent report from the prospective observational Adult/Adolescent Spectrum of HIV Disease cohort study, which described the incidence of opportunistic infections from 1992 to 1997 in more than 22,000 patients, with nearly 36,000 person-years of follow-up.6 The incidence of all opportunistic infectionsdecreased by 55 percent from 1992 to 1997 (highly active antiretroviral therapy first became commercially available in 1995). The percentage decline was steeper for some opportunistic infections, such as Mycobacterium avium complex and cytomegalovirus infections, than for others, such as Pneumocystis carinii infection (Fig. 1). Cytomegalovirus retinitis had the greatest rate of decline, and non-Hodgkin’slymphoma had the least among those reported elsewhere.11-14 The variation among rates of decline in the incidence of specific opportunistic infections in patients receiving highly active antiretroviral therapy suggests that the immune reconstitution induced by this therapy does not protect equally against all opportunistic complications. However, other factors, such as greater use ofantimicrobial prophylaxis or changes in diagnostic and therapeutic approaches, may also have a role in this variation. In 1997, despite the reductions in the incidence of opportunistic infections attributed to highly active antiretroviral therapy, the absolute rates of these infections were still high. P. carinii pneumonia, for example, occurred at a rate of 46 cases per 1000 patient-years.6 In 1997 the...