Children and HIV

Growth of human immunodeficiency virus-infected children receiving HAART.

Study Question: How does treatment with highly active antiretroviral therapy (HAART) affect the height and weight growth of children with HIV infection?

Study Participants: The study included 192 children with HIV infection ages 4 months to 17 years with mild to moderate immunosuppression who were enrolled in a clinical trial to initiate HAART (PACTG 377). Children were randomly assigned to one of four HAART regimens. They had previously received other antiretroviral regimens (NRTI only) for at least 16 weeks.

Study Methods:

	Children were followed for 48 weeks initially and 112 children continued to be followed until 96 weeks. Children's height and weight, viral load, CD4+ count and adverse experience with ARVs were monitored throughout the study.
	Height, weight, and body mass index (BMI) were analyzed for age-and gender- adjusted score based on norms for children in the U.S. population (z scores).

Study Findings:

	Children in the study were predominantly black (65%) and CDC disease category A. About half were over age 6.
	At study entry, their average weight was marginally within normal range at the 44th percentile. Height was significantly below normal at the 29th percentile. BMI was above normal because they were short for their weight. Children with greater viral loads when the study began were significantly shorter and lighter than children with smaller viral loads.
	Administration of HAART led to an increase in mean weight z scores to normal values by week 48. Children whose weight was below the 50th percentile showed more improvement. By week 96 of receiving HAART, the children had increased in mean height z scores to 72% of normal values. Younger children gained height more rapidly, and children with greater baseline viral loads gained weight more rapidly.
	There was no evidence of difference in height or weight changes in 48 weeks between children with different degrees of virologic control.

Limitations: The study was not designed to evaluate the impact of HAART on growth so the authors consider it a hypothesis-generating study. Only slightly more than half the children continued in the study until 96 weeks making that data less reliable.

Lessons Learned:

	Children who had been receiving antiretroviral therapy, but not HAART, were short for their weight. HAART improved the average weight gain of HIV-infected children from subnormal to normal after 1 year and improved average height growth to nearly normal after 2 years.
	The authors recommend additional refinement of HAART treatment strategies to ensure that growth in height is as normal as possible. They note that the goal is to develop treatments that permit HIV-infected children to live lives that are as normal as possible.

Source: Nachman SA, Lindsey JC, Moye J, Stanley KE, Johnson GM, Krogstad PA, Wiznia AA;Pediatric AIDS Clinical Trials Group 377 Study Team. Growth of human immunodeficiency virus-infected children receiving highly active antiretroviral therapy. Pediatr Infect Dis J. 2005 Apr;24(4):352-7.

Prevalence of elevated cholesterol and associated risk factors among perinatally HIV-infected children (4-19 years old) in Pediatric AIDS Clinical Trials Group 219C

Study Question: How common is hyperchohlesterolemia (high cholesterol) among HIV-infected and uninfected children enrolled in a long-term follow-up study? What characteristics, including antiretroviral therapy, are associated with high cholesterol in children with HIV infection?

Study Participants: The 1812 HIV-infected children and 187 uninfected children were part of a larger prospective study (PACTG 219) that is examining long-term outcomes in children born to HIV-infected women.

Study Methods:

	The first cholesterol measurement after a child was enrolled in PACTG 219 was used for analysis. The data from that specimen were linked to other clinical and laboratory data.
	Adherence to antiretroviral therapy (ART) was assessed using a questionnaire developed for the larger study. A child was classified as adherent if the child or parent reported no missing ARV doses in the previous three days.

Study Findings:

	Among children with HIV, 229 (13%) had elevated cholesterol levels compared to 9 (5%) of the uninfected children. Hypercholesterolemia was most common among whites, then Hispanics, then blacks and was more common among the youngest children.
	Low viral load and increased CD4 count were associated with high cholesterol. A 3-day self report of perfect adherence with ART was associated with higher prevalence of high cholesterol.
	Current use of a protease inhibitor (PI) was strongly associated with high cholesterol-five times higher among current PI users. Higher cholesterol was also found among current users of nonnucleoside reverse transcriptase inhibitors (NNRTIs) but seemed to be related to also using a protease inhibitor (PI).

Limitations: The study focused on total cholesterol and did not look at other metabolic problems such as fat maldistribution or high triglycerides. Adherence was assessed only by self-report, although it was consistent with laboratory measures, but might be misreported. As a cross-sectional analysis, the study does not look at the incidence of high cholesterol over time.

Lessons Learned:

	Among children with HIV, the strongest associated risk for high cholesterol was current use of a PI.
	The children who achieved the goal of therapy-a viral load <400 copies/mL had the highest prevalence of high cholesterol (24%). The increased risk of high cholesterol among younger and non-Black ethnicity may be due to better adherence reported by caregivers of those children.
	The potential future health impact of high cholesterol related in ART in children with HIV is cause for concern, particularly because the youngest patients, who will ultimately be on ART the longest, were most likely to have high cholesterol.

Source: Farley J, Gona P, Crain M, Cervia J, Oleske J, Seage G, Lindsey J; Pediatric AIDS Clinical Trials Group Study 219C Team. Prevalence of elevated cholesterol and associated risk factors among perinatally HIV-infected children (4-19 years old) in Pediatric AIDS Clinical Trials Group 219C. J Acquir Immune Defic Syndr. 2005 Apr 1;38(4):480-7.

Pediatric adherence: Perspectives of mothers of children with HIV

Study Question: From a mother's perspective, what is involved in the daily life experience of giving or supervising a child's HIV medication? What can we learn about what promotes or impedes adherence?

Study Participants: The 97 mothers (biologic, adoptive, foster, or other female relatives) in this study are part of the Maternal Caregivers Study of 300 mothers of children with HIV, other chronic illnesses, and healthy children.

Study Methods:

	Mothers were interviewed one to three times over three years and asked about their experience of caregiving, psychosocial resources, coping processes, and mental and physical health.
	Qualitative analysis techniques were used in this study. Two questions guided analysis: What thoughts and feelings do the mothers attach to the medications? What characterizes the interaction between mother and child around giving medications?

Study Findings: Four themes emerged about dealing with medication on a daily basis that had an impact on the mothers' adherence practices:

1. Mothers' attitudes and feelings related to adherence practices. Included in this were mothers' beliefs about the effectiveness of medication and concerns about stigma.


2. The impact of the medications on adherence practices. While palatability of medications was mentioned by about a third of mothers, they saw it as a challenged to be mastered. Side effects, such as diarrhea and vomiting, were more of an issue.


3. Interactions of mothers and children related to adherence practices, including how the mother responded when the child resisted.


4. Developmental issues and responsibility for medication adherence particularly as children reached adolescence.

These themes show how adherence is influenced by complex factors that may change over time. The study found that mothers' commitment to adherence had a positive impact on adherence practices. Feelings of stigma and guilt, the effects of bereavement on children, and children adopting their mothers' attitudes about medications had a negative impact on adherence.

Limitations: The study did not measure adherence directly and did not ask specifically about adherence. They relied on mothers' responses to questions. Mothers who did not have difficulty with giving medication might not have discussed it in their interview. The participants were only followed for six months so changes in the significance of medication or adherence practices could not be measured over time.

Lessons Learned:

	The interactive process of giving medication was shaped by children's behavior, mothers' developmental expectations for children, and, for mothers with HIV, their adherence for themselves. The authors suggest that successful resolution of guilt over having infected their child might influence commitment to adherence among mothers with HIV.

Source: Wrubel J, Tedlie Moskowitz J, Anne Richards T, Prakke H, Acree M, Folkman S. Pediatric adherence: Perspectives of mothers of children with HIV. Soc Sci Med. 2005 Jun 1