Anti-HIV Therapy for Kids Prevents Opportunistic Infections

BOSTON, July 18 -- The modern era of anti-HIV treatment has dramatically reduced the rate of opportunistic infections among HIV-positive children and adolescents, according to researchers here.

For the most common infections, children and adolescents treated with highly active anti-retroviral therapy (HAART) have had significant declines compared with children before the HAART era began in 1996, found Philimon Gona, Ph.D., of the Harvard School of Public Health and Boston University here.

Because of advances in therapy, opportunistic and other infections are uncommon in HIV-positive children today, as well as being lower than in the pre-HAART era, Dr. Gona and colleagues reported in the July 19 issue of the Journal of the American Medical Association.

The researchers arrived at their conclusions by retrospectively studying the rate of 29 infections in 2,767 HIV-infected infants, children, and adolescents who were enrolled in the Pediatric AIDS Clinical Trials Group (PACTG) 219C from Jan. 1, 2001, to Dec. 31, 2004. PATCG 219C is a continuing prospective cohort study with the aim of studying the long-term consequences of HIV infection, treatment effects, and interactions of HIV disease and therapy in American infants, children, and adolescents.

For comparison rates, the researchers used a meta-analysis, published in 2000, of 3,331 HIV-infected children who had participated in PATCG clinical trials.

The main outcome measure was the first occurrence in a study participant of each of the 29 targeted infections.

During the study period, 553 first episodes of a specific infection occurred among 395 (or 14%) of the study participants. The four most common first-time infections which bacterial pneumonia, herpes zoster, dermatophyte infections, and oral candidiasis, with 123, 77, 57, and 52 cases respectively, the researchers said.

The incidence rates per 100 person-years were 2.15 for bacterial pneumonia, 1.11 for herpes zoster, 0.88 for dermatophyte infections, and 0.93 for oral candidiasis.

The incidence rates of first bacteremia, Pneumocystis jeroveci pneumonia, disseminated Mycobacterium avium complex, lymphoid interstitial pneumonitis, systemic fungal infection, cytomegalovirus retinitis, and tuberculosis were all less than 0.50 per 100 person-years, the researchers reported.

By contrast, the pre-HAART incidence rates were 11.1 cases per 100 person-years for bacterial pneumonia, 3.3 for bacteremia, 2.9 for herpes zoster, 1.8 for disseminated M. avium complex, 1.3 for P. jeroveci, 1.2 for oral candidiasis, 0.5 for cytomegalovirus retinitis, and 0.2 for tuberculosis.

With the exception of systemic fungal infection, all of the declines were statistically significant at P<0.001, Dr. Gona and colleagues reported. No such trend was seen for systemic fungal infection, probably because only eight cases were seen pre-HAART and six post-HAART.

"Clearly, antiretroviral medications work," commented Joseph Harwell, M.D., of Brown Medical School in Providence, R.I., and Stephen Obaro, M.D., Ph.D., of the Children's Hospital of Pittsburgh in an editorial. The study by Dr. Gona and colleagues shows that "antiretroviral therapy can reduce infectious complications even for common childhood illnesses, such as bacterial pneumonia and bacteremia."

However, they noted, there are only about 11,000 cases of pediatric HIV infection in the U.S., as a result largely of prophylactic measures that reduce perinatal transmission, and the proportion is declining, compared with adult infections.

But in the rest of the world, 2.3 million children do not have access to HAART or, often, any therapy at all, they said. The central question, then, is "when they will receive (and, like their counterparts in the study by Gona et al, benefit from) the therapy that will allow them to reach adulthood."