HAART use associated with reduced infections in children

September 2006

Since the introduction of highly active antiretroviral therapy (HAART) 10 years ago, there has been a substantial reduction of opportunistic infections and other infections, such as pneumonia, disseminated mycobacterium avium and other non-tuberculosis mycobacteria in children living with HIV.

“Opportunistic infections and other related infections are uncommon in children in the HAART era, and infection rates continue to be lower than those reported in the pre-HAART era,” said Philimon Gona, PhD, of the Harvard School of Public Health and Boston University, and colleagues.

The HIV epidemic has spurred the development of new antiretroviral, immune and vaccine-based therapies geared to block transmission, prevent disease progression and prolong the survival of those living with the virus. The introduction of HAART has allowed patients to live longer, healthier and more productive lives than ever before, with delayed progression to AIDS and lower rates of AIDS-related opportunistic infections and deaths in adults.

Although HAART has dramatically decreased morbidity and mortality in infants, children and adolescents in the United States living with HIV, no studies comparing the incidence rates (IRs) of opportunistic and other related infections before and during the HAART era have been conducted. Gona and colleagues estimated the rates for the first occurrence of 29 targeted opportunistic and other related infections between Jan. 1, 2001 and Dec. 31, 2004, in U.S. infants, children and adolescents with HIV enrolled in Pediatric AIDS Clinical Trials Group 219C (PACTG 219C) to compare the rates in the HAART era to those of the pre-HAART era. PACTG 219C is an ongoing NIH-sponsored study designed to evaluate the long-term consequences of HIV infection, treatment effects and HIV interactions in infants, children and adolescents in the United States.

Infections in pre-HAART vs. HAART era

The ongoing, multicenter, prospective cohort study included 2,767 children aged 0 to 21 years enrolled between Sept. 15, 2000 and Dec. 31, 2004, with data entered in the database up to Aug. 1, 2005, when researchers conducted data analysis. The pre-HAART era comparison population included 3,331 children enrolled in 13 PACTG protocols from October 1988 to August 1998.

In the HAART era study, Gona and colleagues enrolled 75% of the children between 2000 and 2001. Ninety percent of the participants acquired HIV perinatally, 59% were black and 52% were girls, and all ranged in age from 6 and 13 years (median 8.2 years), according to the study.

The most common infections reported by at least 5% of the children that occurred prior to study entry included oral candidiasis, bacterial pneumonia, dermatophyte infections, varicella, lymphoid interstitial pneumonitis, herpes zoster, bacteremia and molluscum contagiosum.

Gona and colleagues found that overall, 553 first episodes of a specific infection occurred among 395 (14%) children and each participant experienced between one and eight first time infections; 286 children experienced only one infection. The four most common first-time infections and their IRs per 100 person-years were bacterial pneumonia (123 children; IR [incident rate], 2.15), herpes zoster (77 children; IR, 1.11), dermatophyte infections (57 children; IR, 0.88) and oral candidiasis (52 children; IR, 0.93). Infection rates were significantly lower than those reported in he pre-HAART era: bacterial pneumonia (IR, 11.1), bacteremia (IR, 3.3), herpes zoster (IR, 2.9), oral candidiasis (IR, 1.2) and tuberculosis (IR, 0.2).

“Despite these current advances due to HAART, some HIV-infected children continue to develop opportunistic infections. Some children fail to respond to antiretroviral therapy as a result of viral resistance, poor adherence, or inability to tolerate complex treatment regimens,” the researchers noted in their Journal of the American Medical Association study. “Furthermore, prophylactic therapies are not fully effective and poor adherence can further reduce their efficacy. Drug interactions, complex dosing schedules, adverse effects, and high costs can further limit the efficacy of these therapies.”

Gona and colleagues recommended continued surveillance of HAART use in children to further assess the long-term effect of the occurrence of infections.

Limited access

In an accompanying editorial, Joseph I. Harwell, MD, assistant professor of medicine at Brown Medical School, Providence, and Stephen K. Obaro, MD, PhD, resident at Children’s Hospital of Pittsburgh, discussed the findings and said although significant advancements have been made for HIV/AIDS patients’ quality of life, challenges remain.

“A cure for HIV infection remains elusive and following infection, chronic suppression of viral replication with preservation of immune function remains the goal. If in the best case scenario, a combination of HAART and specific opportunistic infection prophylaxis continues to prolong survival, patients must contend with the adverse effects of long-term treatment with these agents, most of which are new and have unknown long-term effects, particularly when administered to young children,” they said in a prepared statement.

In 2005, more than 2.3 million children were living with HIV worldwide and 380,000 died, most of which were due in part to severe manifestations of common childhood illness like diarrhea, acute respiratory infection, malnutrition and tuberculosis, according to the editorial. Although rates of HIV cases among children are decreasing in the United States, due to HIV testing and antiretroviral treatment for pregnant women and the fact that children with HIV are becoming adults, cases continue and concerns persist.

“In the past five years, the debate has begun to shift from whether these treatments can be provided in developing countries to how these treatments can be provided. Through [various] programs … the issues of ‘how’ to provide treatment are gradually being addressed, but these efforts need to be increased substantially. For 2.3 million children living with HIV infection worldwide, the question is not whether or how but when they will receive the therapy that will allow them to reach adulthood.”

For more information:

• Gona P, Van Dyke RB, Williams PA, et al. Incidence of opportunistic and other infections in HIV-infected children in the HAART era. JAMA. 2006;296:292-300.
• Harwell JI, Obaro SK. Antiretroviral therapy for children. JAMA. 2006;296:330-331.