Children and HIV

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children with Perinatally Acquired HIV Infection

Study Question(s): How does the quality of life (QOL) of school-aged children with perinatally acquired HIV infection differ between children receiving protease inhibitor combination therapy (PI therapy) and those on antiretroviral treatment without PIs? Also, how does the severity of illness affect QOL?

Study Participants: Data from 940 children, 5 to 18 years of age, who were enrolled in Pediatric AIDS Clinical Trials Group Late Outcomes Protocol 219 was used for the analysis.

Study Methods: Caregiver-reported QOL, as assessed with the General Health Assessment for Children, during 1999 was used for the analysis. The General Health Assessment for Children is an age-specific QOL assessment that was developed for the study with previously validated measures. Sociodemographic characteristics and severity of illness indicators were taken into account when the data were analyzed. The Behavior Problems Index was used to assess psychologic functioning.

Study Findings: QOL among children receiving PI therapy differs little from that among children receiving non-PI therapy, despite indications of more advanced disease. Health perceptions, physical functioning, psychologic functioning, social/school functioning, and overall HIV symptom scores did not differ between groups. Severity of illness was associated with QOL in all areas except psychologic functioning-with more severe illness associated with worse QOL. The study found no evidence of direct negative effects of PI therapy on QOL outcomes, other than an increased rate of diarrhea.

Limitations: Previous PACTG 219 studies have shown that children who are sicker are more likely to receive protease inhibitors. This study used statistical adjustments to address this issue and also looked at relationships between severity of illness-which is affected by PI therapy-and QOL. However, because the study uses a cross-sectional analysis, it isn't possible to identify changes in QOL associated with receiving PI therapy.

Lessons Learned: Findings suggest that the effects of PI combination therapies to slow or to prevent disease progression and to increase CD4+ cell counts and height growth have the potential to improve QOL among children with HIV infection. However, many children do experience behavioral problems and clinical symptoms, with limitations in activities and school performance. Comprehensive health services will continue to be required to minimize long-term illness and disability and to maximize children's potential as they move into adolescence and adulthood.

Source: Storm DS, Boland MG, Gortmaker SL, He Y, Skurnick J, Howland L, Oleske JM; Pediatric AIDS Clinical Trials Group Protocol 219 Study Team. Protease inhibitor combination therapy, severity of illness, and quality of life among children with perinatally acquired HIV-1 infection. Pediatrics. 2005 Feb; 115(2):e173-82. Epub 2005 Jan 3.

Cancer in Perinatally HIV-Infected Children in the United States

Study Question(s): How often does cancer occur in children with perinatally acquired HIV infection in the United States? What is the relationship between immunologic status, HAART, and cancer in these children?

Study Participants: 2969 children from the Pediatric AIDS Clinical Trials Group (PACTG) protocol 219/219C group enrolled 1993 through 2003. This study was restricted to perinatally HIV-infected children in the 219/219C group. Subjects were followed for approximately 3.2 years.

Study Methods: The prevalence of cancer and the occurrence of new cases of cancer (incidence) were examined in the overall group and by sex, race, age, histology, and antiretroviral treatment era (pre-HAART 1993-1997; HAART, 1998-2003). In this study, HAART was defined as an antiretroviral regimen consisting of at least 3 drugs from 2 different classes. Rates of cancer in the study group were compared to data about cancer rates in uninfected children in the general U.S. population.

Study Findings: There were 37 cancers diagnosed in 2969 children. Seventeen children had cancer at the time of enrollment (prevalence = 0.6%) and 20 children developed cancer during follow-up (incidence=1.56/1000 person-years).

	Children with HIV infection had a markedly higher incidence of cancer than uninfected children particularly for lymphoma.
	Rates of soft tissue cancer or leukemia did not differ by HIV infection status.
	Occurrence of new cancer cases did not differ according to sex, race, age or HAART era. Of the cases, 35% were immunocompetent, 25% were moderately immunosupressed and 40% were severely immunosuppressed at diagnosis.
	Cancer rate was 3.09 times higher in children with < 2 years of HAART as compared to children > 2 years of HAART.
	Cancer occurred in children at all levels of immunosuppression.
	Rate of cancer was about three times higher in children with severe immunosuppression at enrollment (CD4+ < 15%) than in children without severe immunosuppression (CD4+% > 15%).

Limitations: There were a low number of cancers in this study, which meant that the researchers could not look at differences in cancer rates by various indicators. Moreover, the observed cancer rates were less than those seen in European studies of HIV-infected children. Some clinicians from the participating institutions have speculated that healthier children have enrolled in the PACTG 219/219C group, particularly in recent years. In addition, sicker children may have been more likely to discontinue study participation during a transition which required re-enrollment from PACTG 219 to 219C beginning in September 2000. Consequently, the cancer rates could be lower if children lost to follow-up were likely to develop cancer.

Lessons Learned: New cancer cases were much higher in HIV-infected children than in HIV-uninfected children. Most cancers in this study were lymphomas (31 of 37) which may reflect the roles of immunosuppression and Epstein-Barr virus infection in the development of cancer in HIV-infected children. Leukemia is the most common form of cancer in HIV-uninfected children. Although the occurrence of cancer did not differ by treatment era, the lower rates of cancer in children receiving HAART for more than 2 years suggests a protective effect of this treatment. Importantly, this study showed that the improved longevity afforded by HAART does not appear to increase the rate of HIV-associated cancers.

Source: Kest H, Brogly S, McSherry G, Dashefsky B, Oleske J, Seage GR 3rd. Malignancy in Perinatally Human Immunodeficiency Virus-Infected Children in the United States. Pediatr Infect Dis J. 2005 Mar;24(3):237-242.