Steep decline in the incidence of nearly all opportunistic infections in HIV-positive children after introduction of HAART

The incidence of most opportunistic infections has fallen significantly in American HIV-positive children, thanks to the use of potent antiretroviral therapy, according to the results of a large prospective study published in the July 19^th edition of the Journal of the American Medical Association. Significant reductions were seen in the incidence of infections common in the era before effective antiretroviral therapy became available, such as bacterial pneumonia, shingles and oral candida. However, 14% of children developed an opportunistic infection in the period of the study, and some infections, including urinary tract infections, molluscum and viral hepatitis predominantly occurred when children had healthy immune systems.

The use of potent antiretroviral therapy has lead to a dramatic fall in the amount of illness and death seen in HIV-positive individuals. However, no studies had looked at the incidence of opportunistic infections in the periods before and after effective HIV treatment became available.

Consequently, investigators from the ongoing Pediatric AIDS Clinical Trial Group (PACTG) 219C study decided to gather data on the incidence of opportunistic infections in children in the eras before and after the availability of potent HIV treatment.

A total of 2,767 children and adolescents aged under 21 years were enrolled in the PACTG 219C study, which was designed to examine the long-term consequences of HIV therapy in children, including the efficacy of treatment and its side-effects. For purposes of comparison, the incidence of opportunistic infections from 13 PACTG trials, involving over 3,330 children, was examined.

Most of the children (90%) in the PACTG 219C study were vertically infected with HIV, 59% were black, 26% Hispanic, and a quarter had a CD cell percentage of 25% or greater, indicating a healthy immune system. The median period of follow-up was 3.4 years. Significant numbers of children had experienced an opportunistic infection prior to entry to the study with 761 having a diagnosis of oral thrush and 700 bacterial pneumonia.

The incidence of opportunistic infections fell significantly with the use of potent anti-HIV treatment. In particular, the investigators noted that the incidence rate of bacterial pneumonia fell from 11 per 100 person years to 2.15 per 100 person years; and, the incidence rate of shingles fell from 3 per 100 person years to 1 per 100 person years. Significant falls were also seen in the incidence of bateraemia, oral thrush, and tuberculosis.

Overall, 14% of children developed an opportunistic infection between 2000 and 2004. The investigators noted that 49% of children who developed an infection did so when they had a CD4 cell percentage of 25% of higher, which theoretically suggests a reduced susceptibility to infections. Indeed, the majority of many milder opportunistic infections including skin urinary tract infections (52%), molluscum (59%), and viral hepatitis (64%) occurred when children had relatively healthy immune systems. By contrast, all but one of the seven cases of PCP pneumonia that occurred were in children with very weak immune systems, indicated by a CD4 cell percentage of 15% or below.

A total of 48 children died during follow-up, the most common causes of death being pneumonia (13 cases), renal disease (six cases), and cardiac disease (five cases). Advanced AIDS, without a specific cause was also given as the cause of death for six children.

After accounting increases in CD4 cell count, the incidence of all opportunistic infections (except systemic fungal infections, the numbers of which were too low to allow for proper statistical analysis), fell significantly (p

Throughout the period of the study, use of potent anti-HIV treatment remained constant with over 80% of children taking therapy. However, the proportion of patients taking prophylactic therapy for PCP, MAI and fungal infections all fell significantly.

Although some children still develop opportunistic infections, and their treatment -due to issues of poor response to treatment, resistance or suboptimal adherence- therefore remains “challenging”, the authors are encouraged by the findings of this study. They conclude, “our findings demonstrate a substantial reduction in the incidence of several opportunistic infections in HIV-infected children since the introduction of HAART therapy.”

An accompanying editorial draws attention to how few of the 2.3 million HIV-infected children in resource-limited countries have access to HIV treatment, but notes that there is a growing consensus that potent HIV treatment can be delivered in poorer countries. The author writes, that for children in these countries, “the question is not whether but when they will receive (and…benefit from) the therapy that will allow them to reach adulthood.”