Effect of specific ART drugs on lipid changes and the need for lipid management in children with HIV.

BACKGROUND: We investigated the effects of individual antiretrovirals on lipids in HIV-infected children and the proportion potentially eligible for dietary or pharmacologic intervention. METHODS: St Mary's and Great Ormond Street Hospital's, London, United Kingdom, patients between 1995 and 2007 were included. Associations between lipids (millimoles per liter) and specific antiretroviral therapy were assessed using mixed-effects models adjusted for confounders. Children eligible for lipid-lowering management were assessed according to American Academy of Pediatric criteria [low-density lipoprotein (LDL) > 190 mg/dL or 4.9 mmol/L for children with no known cardiovascular disease risk factors or LDL > 160 mg/dL or 4.1 mmol/L for children with 2 or more cardiovascular disease risk factors]. RESULTS: Four hundred forty-nine children had median 4.5-year follow-up. On average, antiretroviral therapy-naive children had normal lipids except for low high-density lipoprotein cholesterol (HDL) (median 0.8). All cholesterol subsets were elevated for the 4 drugs assessed. Protease inhibitors had greater rises in total cholesterol with the maximal non-HDL rise for lopinavir/ritonavir at 4+ years of exposure, 0.8 (0.57-1.03). The nonnucleoside reverse transcriptase inhibitors also raised non-HDL, but this was associated with additional clinically significant increases in HDL. Nevirapine raised non-HDL by 0.38 (0.09-0.31) at 2-3 years and HDL by 0.34 (0.28-0.41). Efavirenz raised non-HDL by 0.2 (0.09-0.31) and HDL by 0.12 (0.08-0.17) at 1 year. Ten percent had LDL above the 95th percentile, but only 3 met the 4.9 cutoff for pharmacologic intervention. CONCLUSIONS: Intervention strategies (dietary and exercise advice, treatment switching, and pharmacotherapy) are required for persistent hyperlipidemia and should be assessed in randomized control trials.

Family saliva sharing behaviors and age of human herpesvirus-6B infection.

OBJECTIVE: Transmission of human herpesvirus (HHV-6) type B is hypothesized to occur via saliva. We sought to determine whether behaviors promoting saliva sharing were associated with HHV-6B infection. METHODS: Parents of young children participating in a natural history study of HHV-6B were asked to complete a questionnaire focused on family behaviors that result in saliva sharing. RESULTS: Of 111 surveys, 109 (98%) were completed. Of the 109 participants, 37 (34%) were infected with HHV-6 before 1 year of age. Having older siblings (adjusted OR 4.1, 95% CI 1.5, 11.8) and receipt of parental saliva when kissed (adjusted OR 5.1, 95% CI 1.8, 14.5) were independently associated with younger age of HHV-6 infection. Dose-response relationships were demonstrated between HHV-6 infection before 1 year and both number of siblings and the frequency that the child received parental saliva when being kissed (p=0.006 and p=0.002, respectively). CONCLUSIONS: Having older siblings and parents who shared saliva increased risk of HHV-6B acquisition in children. These data support the hypothesis that HHV-6 is transmitted primarily via saliva within families.

Polymerase chain reaction diagnosis of primary human herpesvirus-6 infection in the acute care setting.

OBJECTIVE: To evaluate the potential utility of identifying primary human herpesvirus (HHV)-6 infection in an emergency department setting by determining the frequency of HHV-6 viremia, diagnostic testing, and empiric treatment of serious bacterial infection (SBI) in HHV-6 viremic children, and concurrent SBI and HHV-6 viremia. STUDY DESIGN: Children under age 2 years and who had a blood specimen taken for evaluation of fever were tested for HHV-6 by polymerase chain reaction (PCR). HHV-6 viremia was defined as detection of HHV-6 DNA in acute plasma. RESULTS: A total of 32 of the 181 subjects (18%) had HHV-6 viremia. Children with HHV-6 viremia frequently underwent procedures for diagnosis and empiric treatment of SBI: 60% had bladder catheterizations, 6% had lumbar punctures, 47% had radiographs, 32% received empiric antibiotics, and 34% were hospitalized. Four of the 32 children with HHV-6 viremia (12.5%) were diagnosed with SBI, although none had a positive culture of blood or cerebrospinal fluid. CONCLUSIONS: Rapid diagnosis of HHV-6 viremia may not serve to adequately differentiate infants with and without SBI in acute care settings. Although no children with HHV-6 viremia had bacteremia or meningitis, it appears that additional criteria are needed to increase the specificity of HHV-6 PCR testing before withholding evaluation for SBI.

A population-based study of primary human herpesvirus 6 infection.

BACKGROUND: Serologic studies indicate that human herpesvirus 6 (HHV-6) infects 90 percent of children by two years of age. Little is known about the acquisition, virologic course, and clinical manifestations of HHV-6 infection. METHODS: We prospectively studied a cohort of 277 children from birth through the first two years of life to define the pattern of acquisition of HHV-6. The children's saliva was tested weekly for HHV-6 DNA with the use of the polymerase chain reaction. Parents maintained a daily log of signs and symptoms of illness in their children. RESULTS: Primary HHV-6 infection occurred in 130 children, with cumulative percentages of 40 percent by the age of 12 months and 77 percent by the age of 24 months. The peak age of acquisition was between 9 and 21 months. The acquisition of HHV-6 was associated with female sex (adjusted hazard ratio, 1.7; 95 percent confidence interval, 1.2 to 2.4) and having older siblings (adjusted hazard ratio, 2.1; 95 percent confidence interval, 1.4 to 2.9). Among 81 children with a well-defined time of acquisition of HHV-6, 93 percent had symptoms, and 38 percent were seen by a physician. None had seizures. As compared with children who had other illnesses, those with primary HHV-6 infection were more likely to have fever (P=0.003), fussiness (P=0.02), diarrhea (P=0.03), rash (P=0.003), and roseola (P=0.002) and were more likely to visit a physician (P=0.003). CONCLUSIONS: The acquisition of HHV-6 in infancy is usually symptomatic and often results in medical evaluation. Roseola occurs in a minority of patients, and febrile seizures are infrequently associated with primary HHV-6 infection. Older siblings appear to serve as a source of HHV-6 transmission.