Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents Initiation of ART in the Setting of an Acute OI (Treatment-Naïve Patients)      The benefits of ART in the setting of an acute OI include the improvement in immune function that would potentially contribute to faster resolution of the OI. The beneficial effect of initiating ART during an acute OI has been best demonstrated for OIs for which limited or no effective therapies are available. Reports detailing the resolution of cryptosporidiosis, microsporidiosis, progressive multifocal leukoencephalopathy (PML), and Kaposi sarcoma after the initiation of potent ART provide evidence that improving immune function can lead to improved outcome in the setting of an acute OI . Another benefit of immediate initiation of potent ART during an acute OI is the reduction in risk for a second OI. Arguments against the immediate initiation of ART concurrent with the diagnosis of an OI include drug toxicities including additive toxicities, distinguishing toxicities caused by antiretrovirals (ARVs) from toxicities related to drugs used to manage OIs, the potential for drug interactions between OI therapies and ART, and the potential for inflammatory immune reconstitution syndromes to complicate the management of the OI in this setting. Much simpler ART regimens are available for the treatment of HIV-1 disease, diminishing the argument to delay therapy for reasons of complexity. However, overlapping toxicities exist between OI treatments and ART regimens that can complicate the ability to identify drug specific toxicity. Drug interactions pose the biggest problem for the treatment of patients with tuberculosis (TB), but ART regimens compatible with TB treatment are available. Immune reconstitution syndromes have been described for mycobacterial infections (including disease caused by Mycobacterium avium complex [MAC] and Mycobacterium tuberculosis, Pneumocystis jiroveci pneumonia (PCP), toxoplasmosis, hepatitis B and hepatitis C viruses, cytomegalovirus (CMV) infection, varicella-zoster virus (VZV) infection, cryptococcal infection and PML. Immune reconstitution syndromes are characterized by fever and worsening of the clinical manifestations of the OI or new manifestations weeks after the initiation of ART. Determining the absence of recrudescence of the underlying OI and new drug toxicity or a new OI is important. If the syndrome does represent an immune reactivation syndrome, adding nonsteroidal anti-inflammatory agents or corticosteroids to alleviate the inflammatory reaction is appropriate. The inflammation might take weeks or months to subside. The largest number of published reports of immune reconstitution syndromes is among patients with TB disease. Patients can experience high fevers, worsening lymphadenopathy or transient-to-severe worsening of pulmonary infiltrates, and expanding central nervous system lesions . Such "paradoxical reactions" might be more common among HIV-1--infected patients with TB disease who were started on potent ART compared with those not started on ART and among patients with TB disease who were not HIV-1-infected . Reduction of HIV-1 RNA levels and marked increases in CD4+ T lymphocyte counts have been associated with the occurrence of paradoxical reactions in patients with TB disease or MAC . Although the majority of reactions occur within the first few weeks after initiation of ART, some have occurred up to several months after the initiation of TB therapy or ART. No randomized controlled trials exist that demonstrate that initiating ART improves outcome for patients being treated with specific therapy for their acute OI. In addition, no data demonstrate that initiation of ART in the setting of an acute OI worsens the prognosis or treatment for that OI. Trials are underway to evaluate the most appropriate timing for initiation of ART in this context.