Initiation of cART for an Acute OI in Treatment-Naive Children
Specific data regarding when to start cART in children with an acute OI and how to manage cART when an acute OI occurs in a child already receiving cART are limited. The benefit of initiating cART is improved immune function, which could result in faster resolution of the OI. This is particularly important for OIs for which effective therapeutic options are limited or not available, such as microsporidiosis, progressive multifocal leukoencephalopathy and Kaposi sarcoma. However, potential problems exist when cART and treatment for the OI (eg, rifampicin-based antituberculous therapy) are initiated simultaneously. These include drug-drug interactions between the ARV and antimicrobial drugs, particularly given the more limited repertoire of ARV drugs available for children than for adults; issues related to toxicity, including potential additive toxicity of ARV and OI drugs and difficulty in distinguishing cART toxicity from OI treatment toxicity and the potential for IRIS to complicate OI management. IRIS is more likely to occur in patients with advanced HIV infection and higher OI-specific antigenic burdens, such as those who have disseminated infections or a shorter time from acute OI onset to start of cART. Most IRIS events have potential to result in significant morbidity but do not result in death; the exception is OIs with central nervous system (CNS) involvement, the form of IRIS most commonly associated with mortality.
The primary consideration in delaying cART until after initial treatment of the acute OI is risk of additional illness or death during the delay. Although the short-term risk of death in the United States during a 2-month cART delay may be relatively low, mortality in resource-limited countries is significant. Randomized trials in adults demonstrate significantly better outcomes when adults with non-CNS OIs begin cART early in the course of OI treatment, but raise concern for potential increased mortality when cART is initiated early in adults (in Africa) with cryptococcal meningitis.[15–17] In the absence of trials in children, recommendations about timing of cART initiation in children undergoing OI treatment are not definitive and management should be individualized and made in consultation with a specialist with expertise in managing HIV and OIs in children. The timing is a complex decision based on the severity of HIV disease, efficacy of standard OI-specific treatment, social support system, medical resource availability, potential drug-drug interactions and risk of IRIS. Most experts believe that the early benefit of potent cART outweighs any increased risk to children who have OIs such as microsporidiosis, progressive multifocal leukoencephalopathy or Kaposi sarcoma for which effective treatment is lacking.
Pediatr Infect Dis J. 2013;32(12):1303-1307. © 2013 Lippincott Williams & Wilkins