Preventing and Treating HIV-Related OIs — Updated Guidelines

On June 18, 2008, the National Institutes of Health, the Centers for Disease Control and Prevention, and the HIV Medicine Association of the Infectious Diseases Society of America released updated guidelines for the prevention and treatment of HIV-related opportunistic infections (OIs). These guidelines have been substantially revised from the 2004 version and incorporate new information on:

• Antiretroviral therapy (ART) as a management strategy for OIs

• Immune reconstitution inflammatory syndrome (IRIS)

• The use of interferon-γ release assays for the diagnosis of latent tuberculosis (TB)

• The management of hepatitis B virus coinfection

• Drug–drug interactions between rifamycin and antiretrovirals during TB treatment

• Malaria

For each HIV-related OI, the guidelines describe clinical presentation, diagnosis, and recommended strategies for preventing exposure to opportunistic pathogens, preventing disease (primary prophylaxis), treating active disease, monitoring for adverse effects (including IRIS), managing treatment failure, and preventing recurrence (secondary prophylaxis). The document also outlines special considerations for managing each OI during pregnancy. Extensive tables outline the specific dosing for treatment and prophylaxis, and clear recommendations are given for when preventive therapy should be started and when, after immune improvement on ART, it should be stopped.

In addition to discussing specific OIs, the guidelines outline the broader controversy surrounding when to start ART in the context of an acute OI. Immediate ART is clearly beneficial — and thus recommended — for progressive multifocal leukoencephalopathy, microsporidiosis, cryptosporidiosis, and Kaposi sarcoma. For other OIs, the risk-benefit balance is still under consideration, although the results of ACTG 5164 certainly support immediate ART. In that randomized trial, patients with acute OIs who received ART immediately had a lower risk for AIDS progression or death than did those who deferred ART until 4 to 6 weeks later (Abstract 142, 15th Retrovirus Conference, 2008).

Comment: This comprehensive (289 pages, 1358 references) overview of HIV-related OIs is an extraordinary resource; it will be useful for all HIV specialists, but perhaps particularly so for those who received their training after 1996, when the incidence of OIs began to decline sharply as a result of effective ART. I suspect that once the findings from ACTG 5164 are more widely incorporated into practice and extended to diverse OIs (most in the trial were Pneumocystis jirovecii pneumonia), the controversy about when to start ART in patients with OIs will fade.