The Changing Face of Mycoses in Patients With HIV/AIDS
The current era of effective antiretroviral therapy has led to a marked reduction in opportunistic infections (OIs) in those countries where such therapies are available. Opportunistic fungal infections are no exception, and the incidence of such infections is now 20% to 25% of that seen in the mid-1990s. Infections associated with very advanced HIV disease, such as azole-resistant candidiasis and aspergillosis, are also rarely seen, reflecting the improvement in immune function. Indeed, the most common issue now is whether patients who have had a systemic mycosis require lifelong therapy as had been recommended. Preliminary data from small studies suggest that as with other OIs, it may be possible to stop suppressive therapy in patients with a history of mycosis whose CD4 lymphocyte count rises with antiretroviral therapy. Thus, it appears that the future of HIV-associated mycoses is linked to the future of effective treatment for HIV itself.
The treatment of HIV infection has evolved remarkably since the introduction of protease inhibitors and nonnucleoside reverse transcriptase inhibitors, either of which, when combined with nucleoside reverse transcriptase inhibitors, constitutes HAART. Since 1996, when HAART became widely used, a dramatic decline in the mortality and morbidity of HIV-infected patients has occurred. This trend has continued, and more recent data indicate up to an 80% decrease in HIV-related mortality. Morbidity from opportunistic infections (OIs), even those that do not have specific therapies, has improved to a rate of approximately 20% of that seen before the introduction of HAART. These observations have also been reported in HIV cohorts from other industrialized nations where potent antiretroviral therapy is available. This decline, in general, is attributable to better care of HIV-infected individuals; use of prophylaxis for OIs; and, most important, the effective use of HAART. HAART is associated with improvement of the immune system, measurable as a quantitative increase in the CD4 lymphocyte subpopulation.
However, despite the encouraging outlook regarding the decline of HIV-related disease, there are certain factors that have continued to cause concern. First, there are estimated to be more than 400,000 persons with known HIV infection in the United States, almost one third of whom have not yet developed AIDS (data reported through June 2000, from the CDC Web site). Second, many undiagnosed cases of HIV infection exist and represent a pool for a continued epidemic and likely future cases of AIDS unless HIV-infected persons are identified and treated. Third, although the incidence of OIs is declining, these infections have not disappeared, even among those who are treated, because of the problems of access to health care, adherence to medication, and resistant HIV disease.
In fact, the spectrum of disease and the relative frequencies of OIs have not changed appreciably since the earlier years of the HIV epidemic, with Pneumocystis carinii pneumonia (PCP), candidal esophagitis, and Mycobacterium avium complex (MAC) infection remaining the most common OIs even in the HAART era. Consequently, judicious application of published treatment guidelines is appropriate for improved care of HIV- infected persons. This article reviews opportunistic mycoses from the perspective of improving immunity in the face of HIV infection, with particular reference to the pathophysiology and clinical implications of this restored immune status.
The current era of effective antiretroviral therapy has led to a marked reduction in opportunistic infections (OIs) in those countries where such therapies are available. Opportunistic fungal infections are no exception, and the incidence of such infections is now 20% to 25% of that seen in the mid-1990s. Infections associated with very advanced HIV disease, such as azole-resistant candidiasis and aspergillosis, are also rarely seen, reflecting the improvement in immune function. Indeed, the most common issue now is whether patients who have had a systemic mycosis require lifelong therapy as had been recommended. Preliminary data from small studies suggest that as with other OIs, it may be possible to stop suppressive therapy in patients with a history of mycosis whose CD4 lymphocyte count rises with antiretroviral therapy. Thus, it appears that the future of HIV-associated mycoses is linked to the future of effective treatment for HIV itself.
The treatment of HIV infection has evolved remarkably since the introduction of protease inhibitors and nonnucleoside reverse transcriptase inhibitors, either of which, when combined with nucleoside reverse transcriptase inhibitors, constitutes HAART. Since 1996, when HAART became widely used, a dramatic decline in the mortality and morbidity of HIV-infected patients has occurred. This trend has continued, and more recent data indicate up to an 80% decrease in HIV-related mortality. Morbidity from opportunistic infections (OIs), even those that do not have specific therapies, has improved to a rate of approximately 20% of that seen before the introduction of HAART. These observations have also been reported in HIV cohorts from other industrialized nations where potent antiretroviral therapy is available. This decline, in general, is attributable to better care of HIV-infected individuals; use of prophylaxis for OIs; and, most important, the effective use of HAART. HAART is associated with improvement of the immune system, measurable as a quantitative increase in the CD4 lymphocyte subpopulation.
However, despite the encouraging outlook regarding the decline of HIV-related disease, there are certain factors that have continued to cause concern. First, there are estimated to be more than 400,000 persons with known HIV infection in the United States, almost one third of whom have not yet developed AIDS (data reported through June 2000, from the CDC Web site). Second, many undiagnosed cases of HIV infection exist and represent a pool for a continued epidemic and likely future cases of AIDS unless HIV-infected persons are identified and treated. Third, although the incidence of OIs is declining, these infections have not disappeared, even among those who are treated, because of the problems of access to health care, adherence to medication, and resistant HIV disease.
In fact, the spectrum of disease and the relative frequencies of OIs have not changed appreciably since the earlier years of the HIV epidemic, with Pneumocystis carinii pneumonia (PCP), candidal esophagitis, and Mycobacterium avium complex (MAC) infection remaining the most common OIs even in the HAART era. Consequently, judicious application of published treatment guidelines is appropriate for improved care of HIV- infected persons. This article reviews opportunistic mycoses from the perspective of improving immunity in the face of HIV infection, with particular reference to the pathophysiology and clinical implications of this restored immune status.
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