Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy.

Since potent HIV protease inhibitor drugs became widely available in early 1996, many HIV clinical specialists have noted a marked decrease in the occurrence of AIDS-related opportunistic infections, and some specialists have reported unusual clinical presentations and manifestations of previously common opportunistic infections. In this article, we will review (1) the available data regarding recent trends in AIDS-related opportunistic infections incidence and manifestations, (2) clinical and immunologic evidence that potent combination antiretroviral therapy can alter the natural history of these opportunistic infections, and (3) the implications of these findings for current patient management practice and future clinical and immunologic research. As a preface to this review, however, it is important to acknowledge that any evaluation of the potential benefit of potent combination antiretroviral therapy in reducing the risk of serious opportunistic infections can be confounded by the concomitant use of prophylactic antimicrobial agents co-administered to prevent specific opportunistic infections. For example, it is standard clinical practice to administer trimethoprim-sulfamethoxazole (or another agent if trimethoprim-sulfamethoxazole cannot be tolerated) to patients with an absolute CD4 lymphocyte count < 200 cells/microliters, unexplained chronic fever or a history of oropharyngeal candidiasis. Similarly, specific antimicrobial prophylaxis to prevent disseminated Mycobacterium avium complex (MAC) infection in patients with absolute CD4 counts < 50 cells/microliters is also a widely recommended guideline. Although the relative efficacies of specific antimicrobial prophylaxis regimens in preventing the most common life- and sight-threatening opportunistic infectious complications of AIDS [Pneumocystis carinii pneumonia (PCP), disseminated MAC infection, and cytomegalovirus (CMV) retinitis] are now well established, these relative efficacies were established in the era before potent combination antiretroviral therapies became available and may not be generalizable to the current era. Nevertheless, for perspective, the reported efficacies of prophylaxis for PCP, disseminated MAC infection, and CMV end-organ disease are summarized in Table 1.