The use of infection prophylaxis has been a major advance in human immunodeficiency virus (HIV) disease. Even prior to the introduction of potent antiretroviral therapies, the morbidity and mortality rates were decreasing presumably due to recognition of pathogens and use of prophylaxis for opportunistic infections. The Centers for Disease Control and Prevention (CDC) published the 2002 update of the United States Public Health Service/Infectious Diseases Society of America guidelines for opportunistic infection prophylaxis in HIV disease. The major update pertains to the data generated since the 1999 edition regarding the safety of discontinuing both primary and secondary prophylaxis for several opportunistic infections. There are some minor differences with regard to duration of time the CD4 count increases above a set threshold before stopping prophylaxis and the duration of treatment for pathogen-specific diseases, most of which can be attributed to the study designs of the prophylaxis discontinuation trials for that specific pathogen.

Primary prophylaxis is that given before development of an infection. The best known and most effective is trimethoprim–sulfamethoxazole (TMP-SMX) prophylaxis against Pneumocystis jiroveci pneumonia, formerly known as Pneumocytis carinii (PCP). TMP-SMX is 90% or more effective and is estimated to add a year to survival in late HIV disease. Other prophylaxes that are highly effective (≥70% efficacy) have now become standard of care in HIV disease: prophylaxis against tuberculosis (TB) if there has been exposure or a positive tuberculin skin test and against disseminated Mycobacterium avium complex (MAC) infection and toxoplasmosis.