Before the advent of HAART, HIV-positive people with low CD4 cell counts often needed preventive drugs, or prophylaxis, to reduce the occurrence of then-common opportunistic infections such as Pneumocystis pneumonia (PCP), Mycobacterium avium intracellulare (MAI), cytomegalovirus (CMV) and toxoplasmosis. The risk of specific opportunistic infections rises once a person's CD4 cell count falls below a certain level. For example, PCP typically occurs in people with less than 200 cells/mm³.

Numerous studies have demonstrated that people who respond to antiretroviral therapy with sustained immune recovery can safely discontinue prophylaxis for opportunistic infections, demonstrating the body's capacity to regain immune function with effective treatment. The benefits of stopping prophylaxis include reduced ‘pill burden’, fewer side-effects, lower risk of drug interactions and reduced cost.