Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team.

One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.

Early cognitive and motor development among infants born to women infected with human immunodeficiency virus. Women and Infants Transmission Study Group.

OBJECTIVE: To examine the frequency, timing, and factors associated with abnormal cognitive and motor development during the first 30 months of life in infants born to women infected with human immunodeficiency virus type 1 (HIV-1). METHODS: Serial neurodevelopmental assessment was performed with 595 infants born to women infected with HIV-1 in a multicenter, prospective, natural history cohort study. Survival analysis methods were used to evaluate 6 outcome events related to abnormal cognitive and motor growth (time to confirmed drop of 1 SD, time to first score <69, and time to confirmed drop of 2 SD) in Bayley Scales of Infant Development Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores among infected (n = 114) and uninfected (n = 481) infants. Proportional hazards modeling was used to evaluate the effects of HIV infection status, prematurity, prenatal exposure to illicit drugs, maternal educational attainment, and primary language. RESULTS: HIV-1 infection was significantly associated with increased risk for all outcome events related to abnormal mental and motor growth. Differences between infected and uninfected infants were apparent by 4 months of age. Prematurity was associated with increased risk for MDI <69 and PDI <69. Maternal education of <9 completed years was associated with increased risk for MDI <69. Neither prenatal exposure to illicit drugs nor primary language other than English was associated with abnormal development. CONCLUSION: A significant proportion of infants with HIV-1 infection show early and marked cognitive and motor delays or declines that may be important early indicators of HIV disease progression. These abnormalities are independent of other risk factors for developmental delay.

Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185.

Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts /=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.

Diagnosis of infection with human immunodeficiency virus type 1 by a DNA polymerase chain reaction assay among infants enrolled in the Women and Infants' Transmission Study.

Early diagnosis of infection with human immunodeficiency virus type 1 (HIV- 1) in young infants is essential to decisions on their medical and social care. Whereas studies have suggested that polymerase chain reaction (PCR) is a sensitive and timely method of diagnosing HIV infection in children, these evaluations have been limited by the number of specimens studied. Recently, Roche Molecular Systems developed a complete HIV-1 DNA PCR testing kit (from specimen preparation to detection). In this study, use of this PCR test kit was evaluated for the detection of HIV infection in infants of seropositive mothers who were enrolled in the longitudinal, multicenter Women and Infants' Transmission Study. A total of 1209 blood specimens from 483 infants were tested and analyzed. The overall sensitivity and specificity of a single PCR test in determining HIV infection status in infants more than 1 but less than 36 months of age were 95% and 97%, respectively. For infected infants 1 to 6 months of age the sensitivity of the DNA-PCR test was 90% to 100%. In a direct comparison with coculture, the Roche DNA-PCR test was significantly more sensitive than coculture in the detection of HIV-1 in infected infants and was equivalent to coculture for the diagnosis of HIV in infants when a standardized algorithm was used to define infection status.

Early detection of human immunodeficiency virus on dried blood spot specimens: sensitivity across serial specimens. Women and Infants Transmission Study Group.

OBJECTIVE: To evaluate the use of dried blood spot (DBS) specimens and the early diagnostic value of the polymerase chain reaction (PCR) for detection of the human immunodeficiency virus (HIV) in DBS specimens collected at predefined age intervals from a large cohort of U.S. infants at risk of congenital or perinatal HIV infection. DESIGN: We assayed available DBS specimens (n = 272) obtained during the first 4 months of life from 144 infants (41 infected, 103 uninfected) born to HIV-infected mothers enrolled in the Women and Infants Transmission Study. The DBS PCR results were compared with infant HIV infection status, PCR on liquid blood, and viral culture results. Analyses also included sensitivity and specificity of assay as related to the age of the infant when the specimen was obtained. RESULTS: The DBS specimen PCR results were concordant with results from liquid blood specimens and with results from viral culture. The DBS PCR was highly specific for all age groups. Sensitivity in detecting HIV infection status rapidly increased during the first month of life, from 19% (5/26) by 1 week to 96% (25/26) by 1 month of age. Specimens obtained on the day of birth or the next day were the least likely to have detectable HIV DNA. CONCLUSIONS: The PCR assay of DBS specimens is a reliable tool for the early diagnosis of HIV infection and has important advantage over that of liquid blood DNA PCR and viral culture. These advantages include a lower volume of blood required for testing, increased safety, and ease of storage or transport of specimens. Thus DBS PCR is a useful test for clinical and epidemiologic tracking of infants at risk of HIV infection.

The utility of IgA antibody to human immunodeficiency virus type 1 in early diagnosis of vertically transmitted infection. National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development Women and Infants Transmission Study Group.

OBJECTIVE: To determine the sensitivity and specificity of anti-human immunodeficiency virus (HIV) IgA in identifying infected infants at or before 6 months of age among the offspring of HIV-infected mothers. DESIGN: Prospective comparison of anti-HIV IgA measurement performed in 2 different laboratories by 2 different methods with the criterion standard of blood culture. SETTING: Five centers in the United States and Puerto Rico. PATIENTS: Population-based sample of 156 infants of HIV-infected mothers in the Women and Infants Transmission Study. MAIN OUTCOME MEASURES: Results of anti-HIV IgA test in relation to the infection status of the infants as measured by blood culture. RESULTS: Six-month plasma or serum samples were first tested in the 2 laboratories. The sensitivity and specificity of anti-HIV IgA in detecting infected infants at this age by laboratories 1 and 2 were 69% and 63% and 100% and 99%, respectively. A look-back study of samples obtained at birth, 1, 2, and 4 months was then performed on all infected children and a matched set of uninfected children. The performance of the test at birth was unsatisfactory in both laboratories (sensitivity 44% and 33%, specificity 43% and 60%), whether peripheral or cord blood was examined. At 1, 2, and 4 months, the sensitivity of the test was lower than at 6 months, but specificity was high. A modest correlation of absent anti-HIV IgA antibody and low percentage of CD4 cells in peripheral blood was seen at 6 months of age. CONCLUSIONS: The anti-HIV IgA test has moderate sensitivity and high specificity for the diagnosis of HIV infection at 6 months of age in the offspring of infected mothers.

Natural history of somatic growth in infants born to women infected by human immunodeficiency virus. Women and Infants Transmission Study Group.

OBJECTIVE: To evaluate the nature and magnitude of the effect of congenitally or perinatally acquired human immunodeficiency virus (HIV) infection on somatic growth from birth through 18 months of age. STUDY DESIGN: Anthropometry was performed serially in 282 term infants born to HIV-infected women in a multicenter prospective natural history cohort study. Repeated measures analysis was used to compare z-score anthropometric indexes of weight-for-age, length-for-age, weight-for-length, and head circumference-for-age between infected and uninfected infants, with adjustment for covariates including infant gender; maternal education; prenatal alcohol, tobacco, and/or illicit drug exposure; and mean prenatal CD4+ T-lymphocyte count. A separate repeated measures model was used to assess the effect of infant zidovudine treatment on growth. RESULTS: Infants infected with HIV were an estimated average 0.28 kg lighter and 1.64 cm shorter than uninfected infants at birth, were 0.71 kg lighter and 2.25 cm shorter by 18 months of age, and had a sustained estimated average decrement of 0.70 to 0.75 cm in head circumference. Patterns of growth were similar in male and female infants. Infected infants had a progressive decrement in body mass index from birth through 6 months of age. Infection with HIV was associated with significant decrements across all standardized growth outcome measures after adjustment for covariates. Mean z scores were lower for weight by 0.612 (p < 0.001), for length by 0.735 (p < 0.001), for weight-for-length by 0.255 (p = 0.02), and for head circumference by 0.563 (p < 0.001) SD units compared with uninfected infants. Zidovudine treatment was not associated with improved growth. CONCLUSION: The effect of congenitally or perinatally acquired HIV infection on infant growth is one of early and progressive decrements in attained linear growth and growth in mass, early and sustained decrements in head growth, and marked early decrements in body mass index.