Antiretroviral Therapy for Children

Abstract

ACCORDING TO THE UNITED NATIONS PROGRAMME on HIV/AIDS (UNAIDS) global report on human immunodeficiency virus (HIV), in 2005 more than 2.3 million children were living with HIV infection, and 380 000 children with HIV had died. Most of the children who die from HIV have severe manifestations of common childhood illnesses, such as diarrhea, malnutrition, acute respiratory tract infection, and tuberculosis. These children often die before the diagnosis of HIV infection can be made, and mortality is often attributed to a background high rate of early childhood mortality. The United States is home for a diminishing proportion of HIV-infected children, with an estimated 11 000 cases in 2005. There are 2 reasons for this decreasing population of HIV-infected children in the developed world. First, pregnant women are increasingly being offered HIV testing, and HIV-infected women are receiving antiretroviral medications sufficient to reduce transmission to a rate of approximately 1% to 2%. Second, the population of HIV-infected children is diminishing because those children who had been infected are now growing up and becoming adults, following the introduction of potent new drugs in 1996. According to a longitudinal study by the Pediatric AIDS Clinical Trials Group (PACTG 219), the mortality rate for HIVinfected children and adolescents decreased from more than 5% in 1996 to less than 1% in 1998. Similar survival benefits have been observed among adults. The impact of highly active antiretroviral therapy (HAART) on survival and quality of life among patients affected by HIV is hardly disputable, but concise objective evidence of the benefit of treatment on infectious complications in children has been lacking in the medical literature. Before the availability of HAART, opportunistic infections such as Pneumocystis jiroveci pneumonia, bacteremia, bacterial pneumonia, and fungal sepsis were significant fatal diseases in patients infected with HIV and remain so among patients not receiving therapy. In this issue of JAMA, Gona and colleagues provide objective evidence to substantiate the benefit of HAART or, more correctly, the association of HAART and opportunistic infection prophylaxis with incidence of opportunistic infections before and after the advent of HAART. In a retrospective cohort study, Gona et al compared the incidence of 29 opportunistic infections in HIV-infected children who were treated in the HAART era with the incidence among those who were treated before the availability of HAART. They found that the incidence of P jiroveci pneumonia had decreased by 14-fold, disseminated Mycobacterium avium complex by 12-fold, bacteremia by 10-fold, and bacterial pneumonia by 5-fold. These reductions in opportunistic infections occurred despite a concomitant reduction in the use of specific prophylaxis medications, suggesting that immune reconstitution rather than improved prophylaxis was primarily responsible for better outcomes. The size and diversity of the population studied allows for generalizability of the results to the US population of children with HIV infection. There were approximately 3000 children in the cohort, which constitutes about 22% of children and adolescents living with HIV in the United States. Given the diminishing population of HIV-infected children, it is unlikely that additional data will become available in this country. There were limitations with the retrospective cohort study design, which evaluated available data from a database. Some events and clinical practices changed over time and could have affected case ascertainment and overall disease incidence. Although the incidence of bacterial pneumonia was reported, the diagnosis of this problem in children is difficult, because no consistent clinical or radiographic features reliably distinguish different etiologies of pneumonia. Radiographic pneumonia may or may not be associated with bacteremia. When such an association occurs, the relationship is not always a causal one. Specific etiologic diagnosis of bacterial pneumonia can be determined by diagnostic techniques, such as lung aspirates or bronchoalveolar lavage. These procedures are highly sensitive but are seldom used because they are considered too invasive.