Despite advances in antiretroviral therapy (ART) and opportunistic infection (OI) prophylaxis and treatment, OIs continue to afflict patients infected with HIV and cause considerable morbidity and mortality in the United States. OIs have been defined as infections that are more frequent or severe because of immunosuppression in HIV-infected people. Before the widespread use of combination ART, OIs were the primary cause of morbidity and mortality in this patient group. However, the use of ART has been associated with drastic reductions in the frequency of HIV-associated OIs and mortality.
Today, HIV-associated OIs continue to occur, primarily because patients are unaware of their HIV infection; in such cases an OI may be the initial indication of HIV disease. They also occur among those who are aware of their HIV infection but do not take ART because of psychosocial or economic factors. There is also evidence suggesting that OIs may occur in patients who take ART but fail to attain adequate virologic and immunologic responses due to adherence, pharmacokinetics, or unexplained biologic factors.
A Necessary Update
The CDC, NIH, and the HIV Medicine Association of the Infectious Diseases Society of America updated guidelines for prevention and treatment of OIs in HIV-infected adults and adolescents (Table 1). The report, published in the March 24, 2009 Morbidity and Mortality Weekly Report and available online at www.cdc.org/mmwr, places greater emphasis on the role of effective ART to prevent and treat acute OIs (Table 2). It also updates information on 29 opportunistic diseases that are of concern for patients infected with HIV/AIDS.
“Much has changed in the field of HIV/AIDS management since the previous guidelines were published,” says John T. Brooks, MD, who was a co-author of the updated recommendations. “It’s critical that healthcare providers recognize the signs and symptoms of OIs—particularly newer physicians who may have less experience with these infections—and provide effective prophylaxis and treatment.”
For each OI discussed in the report, recommendations are provided that address: 1) preventing exposure to opportunistic pathogens, 2) preventing disease, 3) discontinuing primary prophylaxis after immune reconstitution, 4) treating patients with disease, 5) monitoring for adverse effects, 6) managing treatment failure, 7) preventing disease recurrence, 8) discontinuing secondary prophylaxis after immune reconstitution, and 9) addressing special considerations during pregnancy. “Major additions to the guidelines include significantly expanded sections addressing hepatitis B virus infection and tuberculosis,” says Dr. Brooks. “The recommendations in regard to prevention and treatment of hepatitis B infection are in line with antiviral treatment guidelines published by the Department of Health and Human Services.”
Taking More Into Consideration
For the first time, the guidelines include information on the diagnosis and management of immune reconstitution inflammatory syndrome (IRIS). “IRIS occurs following the initiation of ART,” Dr. Brooks says. “As the immune system begins to recover, it can respond with an overwhelming inflammatory response to an OI that makes the symptoms of infection worse,” says Dr. Brooks. “Diagnosis of IRIS is clinically challenging. It involves differentiation of progression of a previously quiescent OI or development of a new OI from unrelated organ dysfunction or drug toxicity. Although no consensus has been reached concerning the optimal time to start ART for a recently diagnosed OI, one recently completed randomized clinical trial suggests that early therapy, within the first 2 weeks, is indicated for an acute OI, with the exception of tuberculosis.”
The expert panel also expanded on drug-drug interactions and adverse events associated with HIV medications. Sections in each chapter on considerations in women who are pregnant were also enhanced. It is recommended that ART with OI therapy be initiated immediately for pregnant women who have a diagnosed OI and are not on ART to minimize the risk for perinatal transmission of HIV. According to the guidelines, decisions about immediate versus delayed initiation of ART in pregnancy should include consideration of gestational age, maternal HIV RNA levels and clinical condition, and potential toxicities and interactions between ART and OI drugs.
Recognizing OIs in HIV-Infected Patients
Strict adherence to immunization recommendations and a continued focus on ART therapy are pivotal for preventing and managing OIs in patients infected with HIV/AIDS. “OIs continue to threaten the health of many HIV patients,” says Dr. Brooks. “It’s important that the clinical knowledge around these infections be passed on to each new generation of physicians so that the presence of an HIV-associated OI can be better recognized and treated.”
John T. Brooks, MD, has indicated to Physician’s Weekly that he has or has had no financial interests to report.
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