A longitudinal assessment of autologous neutralizing antibodies in children perinatally infected with human immunodeficiency virus type 1

The evolution of autologous neutralizing antibodies to sequential human immunodeficiency virus type 1 (HIV-1) isolates was studied in a population of 16 children who were perinatally infected with human immunodeficiency virus type 1. The cohort included seven children with rapid disease progression (RP) and nine who had nonrapid disease progression (NRP). Four of the NRP after 6 months of age harbored viruses that could be neutralized by antibodies found in autologous contemporaneous plasma (titers up to 1:640) while the majority of longitudinally collected viruses from five NRP were resistant to neutralization with contemporaneous plasma. Because of their shorter survival, only five of the RP had studies after 6 months of age; three of the five had neutralizing antibodies to contemporaneous virus isolates and the highest titers were 1:20. The highest titers in RP (up to 1:160) occurred in specimens obtained prior to 6 months of age but these were most likely of maternal origin. Most isolates that were not neutralized by contemporaneous plasma could be neutralized using noncontemporaneous plasma obtained months to years after the virus isolates. These autologous noncontemporaneous neutralizing antibodies persisted for years, had titers that were higher to viruses isolated at younger ages, and were generally more potent in children with NRP than RP. Demonstration of neutralizing antibodies to viruses previously resistant to neutralization by contemporaneous plasma suggests a continuous evolution of virus variants in vivo that are able to escape the effect of neutralizing antibodies

Cellular Tropisms and Co-receptor Usage of HIV-1 Isolates from Vertically Infected Children With Neurological Abnormalities and Rapid Disease Progression

The longitudinal evolution of HIV-1 phenotypes was studied in a cohort of six vertically infected children with early onset and rapid progression of clinical disease. Among 30 viral isolates obtained from peripheral blood, tropisms for both human blood-derived cells (macrophages, T-lymphocytes), and for human neural (brain-derived) cells (microglia, astrocytes) were determined, as was chemokine co-receptor usage. All children harbored from birth macrophage-tropic isolates using the CCR5 co-receptor. Two children later developed T-cell tropic isolates with CXCR4 and CCR3 usage. While all six patients developed neurological abnormalities, only three produced neural cell tropic isolates, which used CCR5. However, early and persistent finding of both astrocyte- and microglia-tropic isolates in one patient did associate with the most rapid progression to brain atrophy among the six patients. Viral phenotypic properties determined in cell culture did not specifically predict clinical features or course, and the development of AIDS did not coincide with, or depend on, the appearance T-tropic, syncytia-inducing viruses

Survival in Children with Perinatally Acquired Human Immunodeficiency Virus Type 1 Infection

We describe our experience at Jackson Memorial Hospital in Miami, Florida, with 172 children who were given diagnoses of perinatally acquired infection with human immunodeficiency virus type 1 (HIV-1). The 146 mothers of the children acquired HIV-1 through heterosexual contact (69 percent), intravenous drug use (30 percent), or blood transfusion (1 percent). The children presented with symptomatic disease at a median age of eight months; only 21 percent presented after the age of two years. The most common first manifestations of disease were lymphoid interstitial pneumonia (in 17 percent), encephalopathy (in 12 percent), recurrent bacterial infections (in 10 percent), and candida esophagitis (in 8 percent), for which the median survival times from diagnosis were 72, 11, 50, and 12 months, respectively. Nine percent of the children had Pneumocystis carinii pneumonia at a median age of five months and had a median survival of only one month. The median survival for all 172 children was 38 months from the time of diagnosis. Mortality was highest in the first year of life (17 percent), and by proportional-hazard analysis the probability of long-term survival is low. In multi-variate analyses, early age at diagnosis and the first identifiable pattern of clinical disease were found to be independently related to survival. We conclude that children with perinatally acquired HIV-1 infection have a very poor prognosis and that most become symptomatic before one year of age. Early diagnosis is important, since there is only a short interval in which to initiate prophylactic or antiviral treatment before progressive disease begins. (N Engl J Med 1989; 321: 1791–6.) HUMAN immunodeficiency virus type 1 (HIV-1) infection and disease have been recognized in pediatric patients since 1983. 1 2 3 The initial reports described children with nonspecific conditions, such as failure to thrive, oral candidiasis, lymphadenopathy, and hepatosplenomegaly, but recurrent infections were also noted, both bacterial and opportunistic. Subsequently, it has been recognized that HIV-1 infection in infants may involve a wide spectrum of clinical disease in multiple systems. 4 , 5 Categorizing the clinical manifestations into patterns of disease provides a means of identifying and classifying infected infants, and such categorization is the basis for the current classification system of pediatric HIV-1 infection of the . . 

Intrauterine herpes simplex virus infections

Neonatal herpessimplexvirus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterineinfection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus