Antiretroviral regimens in pregnancy and breast-feeding in Botswana.

BACKGROUND: The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS: We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS: The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS: All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)

Impact of GB virus type C infection on mother-to-child HIV transmission in the Women and Infants Transmission Study Cohort.

BACKGROUND: GB virus type C (GBV-C) viraemia is associated with a beneficial outcome in HIV-infected individuals in several though not all studies. GBV-C viraemia was examined in a matched case-control study of 133 HIV-infected pregnant women who transmitted HIV to their infants ('cases') and 266 non-transmitting controls. METHODS: HIV-infected children and controls were pair-matched for high-risk delivery, race and year of delivery. GBV-C status was determined in maternal plasma samples obtained at or within 3 months of delivery. RESULTS: Pregnant women with GBV-C viraemia (11% of those studied) had lower HIV RNA levels (P=0.01) and higher CD4 percentages (P=0.0006) [corrected] than women without GBV-C. A trend towards decreased mother-to-child transmission in the multivariate analysis was observed among GBV-C viraemic women delivering after highly active antiretroviral therapy (HAART) became available [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.08-1.05; P=0.06], but not in women delivering prior to the widespread use of HAART. CONCLUSIONS: GBV-C viraemia was associated with a beneficial effect on CD4 percentage and HIV RNA level in these pregnant women, and was also associated with a trend towards reduced risk of mother-to-child HIV transmission among women after HAART became available. Further studies with larger or multiple cohorts are necessary to assess possible benefits in this population.

Reducing perinatal transmission of HIV: early diagnosis and interventions during pregnancy.

This article reviews the New York State regulations regarding expedited testing of newborns for exposure to HIV. Included is a review of statistics as well as the medical and obstetric management of HIV positive pregnant women, including route of delivery. The professional responsibility of midwives, physicians, and other clinicians regarding maternal and neonatal health care is emphasized, especially in states without expedited testing.

The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women. Women and Infants Transmission Study Group.

BACKGROUND: Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. METHODS: The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at approximately 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. RESULTS: Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 microg/ml) than among uninfected children (2.70 microg/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P > or = 0.48). The proportion of children with antibody concentrations > or = 1.0 microg/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P=0.81). CONCLUSIONS: These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued.

Neonatal hypoperistalsis associated with perinatal zidovudine administration.

OBJECTIVE: This paper presents the cases of two infants exposed to perinatal zidovudine in whom hypoperistalsis and intestinal pseudoobstruction developed. STUDY DESIGN: Clinical case reports were prepared of two infants born to women infected with human immunodeficiency virus who were treated with perinatal zidovudine at a single inner-city medical school. RESULTS: None of the previously described causes for this rare condition contributed to the symptoms in these two infants. In addition, the symptoms resolved shortly after discontinuation of zidovudine administration. CONCLUSIONS: Although a strict cause-and-effect relationship between the medication and the impairment in intestinal peristalsis was not proved, awareness of this association should be helpful for physicians caring for infants exposed to perinatal zidovudine.

Viral load and disease progression in infants infected with human immunodeficiency virus type 1. Women and Infants Transmission Study Group.

BACKGROUND: There are only limited data on human immunodeficiency virus type 1 (HIV-1) RNA in perinatally infected infants. Understanding the dynamics of HIV-1 infection and its relation to disease progression may help identify opportunities for effective antiviral treatment in infected infants. METHODS: We obtained plasma samples from 106 HIV-infected infants at birth; at 1, 2, 4, 6, 9, 12, 15, and 18 months of age; and subsequently every 6 months. HIV-1 RNA was assayed by means of a reverse-transcription polymerase chain reaction. The infants were born between 1990 and 1993, and only 21 percent of the infants' mothers received any treatment with zidovudine during pregnancy. RESULTS: Plasma HIV-1 RNA levels increased rapidly after birth, peaked at 1 to 2 months of age (median values at 1 and 2 months, 318,000 and 256,000 copies per milliliter, respectively), and then slowly declined to a median of 34,000 copies per milliliter at 24 months. Newborns with a first positive HIV-1 culture within 48 hours after birth had significantly higher HIV-1 RNA levels, although only during the first two months of life, than those with a first positive culture seven or more days after birth. Infants with a rapid progression of disease had higher peak HIV-1 RNA levels in the first two months of life than those without rapid progression (median value, 724,000 vs. 219,000 copies per milliliter; P=0.006), as well as a higher geometric mean value during the first year of life (median value, 330,000 vs. 158,000 copies per milliliter, P=0.001). CONCLUSIONS: In perinatally infected infants, HIV-1 RNA levels are high and decline only slowly during the first two years of life. Infants with very high viral loads in the first months of life are at increased risk for a rapid progression of disease, which suggests that early treatment with antiretroviral agents may be indicated for these infants.

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.

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.

Blood culture in the first 6 months of life for the diagnosis of vertically transmitted human immunodeficiency virus infection. The Women and Infants Transmission Study Group.

Serial blood cultures over the first 6 months of life in 310 infants with vertical exposure to human immunodeficiency virus (HIV) in the Women and Infants Transmission Study were analyzed to determine their value for early diagnosis of HIV infection. Cultures were done at 0-7 days and 1, 2, 4, and 6 months of age: 55 infants were infected. Blood culture sensitivity in infected children was 24% (7/29) during the first week of life and 85%, 91%, 82%, and 88%, respectively, at 1, 2, 4, and 6 months. The sensitivity, specificity, and positive and negative predictive values of a single culture between 1 and 6 months of age were, respectively, 86.9%, 99.6%, 97.9%, and 97.5%. Two negative cultures between 1 and 6 months of age defined an uninfected infant with a specificity of 99.2%-100.0%. Blood culture done between 1 and 6 months of age in children of HIV-positive mothers is a sensitive and specific test for HIV infection, with high positive and negative predictive values.