Reconstitution of immunity against opportunistic infections in the era of potent antiretroviral therapy.

Critical questions remain unanswered regarding the safety and efficacy of withdrawing primary and secondary prophylaxis in the context of HAART-associated immune reconstitution. What are the mediators of first phase cellular increases? Will continued HIV suppression result in continued immune restoration? And what are the immunological consequences of viral rebound despite HAART in patients whose CD4 counts remain elevated? Can immunity, once lost, be restored by reintroduction of antigens such as by tetanus or pneumococcal vaccination? Can immunoassays predict who will relapse or reactivate an OI? Is it possible to eradicate infections such as MAC, cryptococcosis, and histoplasmosis? Certainly, one can never eradicate CMV infection but can immunoassays predict who will have disease-reactivate? Unfortunately, various studies have reported contradicting results regarding the immunological response in vitro to specific antigens. Until these immunoassays become standardized and validated, it is unclear if immunoassays will be predictive of who would be at risk of development of disease or relapse. Therefore, until such time, clinicians may want to initiate and maintain primary prophylaxis in HIV-infected individuals as recommended by the USPHS/IDSA guidelines based on the nadir CD4+ T-cell count at least until studies have clearly demonstrated whether the increased CD4+ T-cell response attributed to HAART does in fact confer protection against these pathogens. Although for some OIs it does appear safe to withdraw primary prophylaxis and probably secondary prophylaxis, the decision to stop prophylaxis or maintenance therapy should be a joint decision by the patient and clinician based on the risks and benefits of stopping the therapy and the availability of close clinical monitoring for evidence of disease.