Polymorphisms in the CCR5 promoter region influence disease progression in perinatally human immunodeficiency virus type 1-infected children.

The effect of CC-chemokine receptor 5 (CCR5) promoter polymorphisms on the natural history of human immunodeficiency virus (HIV) disease was studied in 73 HIV-1-infected children. The CCR5(59338-59537) promoter haplotype, CCR5-59029A/G polymorphism, and CCR5Delta32 and CCR2-64I alterations were investigated. After exclusion of carriers of CCR5Delta32 or CCR2-64I, Kaplan-Meier analysis disclosed that children with the P1/P1(59353C,59356C,59402A) genotype progressed faster to disease than did children with other haplotypes (P=.016). When CCR2-64I carriers were included, this effect had borderline significance (P=.065) and was lost when CCR5Delta32 carriers were also considered (P=.387). The P1/P1 effect was strongest early after infection, when progression to disease was mainly associated with CCR5 coreceptor-using viruses. These results indicate that the P1/P1 genotype is predictive of rapid progression in HIV-1-infected children lacking CCR5Delta32 or CCR5-64I alleles. The observation of a linkage disequilibrium between P1 and 59029A might explain the previously reported association between 59029A homozygosity and rapid disease progression.

Vulvar carcinoma in a 12-year-old girl with vertically acquired human immunodeficiency virus infection.

We report the first case of a girl with vertically acquired human immunodeficiency virus (HIV) infection, who developed invasive squamous cell carcinoma of the vulva at 12 years of age. Lesions resembling bowenoid papulosis covered the perianal area as well. She underwent a nonmutilating surgical excision of the infiltrating lesion. More than 3 years later, her clinical condition is excellent, although dysplastic, noninfiltrating multifocal lesions persist. This case highlights the need to perform careful periodic genital examinations in all HIV-infected children and adolescents born to HIV-positive mothers.

HIV: mother to child transmission, current knowledge and on-going studies.

It is estimated that approximately 6000 women of childbearing age, mostly living in the developing world, acquire HIV infection every day. Taking into account that approximately 98% of HIV infected children have acquired HIV from the mother, during pregnancy, at delivery or through breastfeeding, therefore, prevention of mother-to-child transmission (MTCT) is a major health priority. Several studies have showed how MTCT of HIV may be prevented using antiretrovirals. Results from a study conducted in Thailand have also recently showed how a short oral zidovudine course during pregnancy and labor may reduce the risk of HIV transmission by approximately 50%. These findings represent a major challenge for the International Health Agencies and Organizations that will have the major obligation to provide HIV tests, counseling and antiviral drugs in settings with high HIV prevalence.

Increased risk of maternal-infant hepatitis C virus transmission for women coinfected with human immunodeficiency virus type 1. Italian Study Group for HCV Infection in Children.

To estimate the risk of mother-to-child transmission of hepatitis C virus (HCV) and identify correlates of transmission, 245 perinatally exposed singleton children followed prospectively beyond 18 months of age were studied. Overall, 28 (11.4%) of the 245 children acquired HCV infection. Transmission occurred in 3 of 80 children (3.7%) whose mothers had HCV infection alone and in 25 of 165 (15.1%; P < .01) whose mothers had concurrent infection with human immunodeficiency virus type 1 (HIV-1). The percentage of HIV-1-infected children was similar (22 of 165, 13.3%), but each virus was transmitted independently; only six infants (3.6%) were coinfected with HCV and HIV-1. The risk of HCV transmission was not associated with maternal HIV-1-related symptoms, intravenous drug use, prematurity, low birth weight, or breast-feeding, whereas it was lower with cesarean section than with vaginal delivery (5.6% vs. 13.9%, P = .06). This suggests that transmission occurs mainly around the time of delivery.

Persistence of antibody responses to Haemophilus influenzae type b polysaccharide conjugate vaccine in children with vertically acquired human immunodeficiency virus infection.

BACKGROUND: Recurrent bacterial sepsis is common in pediatric HIV infection and immunization against Haemophilus influenzae type b (Hib) is recommended. Long term persistence of anti-Hib antibody and the need for, or timing of, a booster dose has not been adequately studied. METHODS: Immunogenicity during a 12-month period following immunization with Hib-tetanus conjugate vaccine (ACT-HIB; Merieux) was evaluated in 48 vertically HIV-infected children and 36 uninfected children, born to HIV-positive mothers. A titer of anti-Hib polysaccharide antibody of > or = 0.15 microgram/ml was considered to indicate short term and > or = 1 microgram/ml long term protection. RESULTS: At 1 month postvaccination 36 (100%) uninfected and 42 (88%) HIV-infected children achieved titers of > or = 1 microgram/ml. However, by 1 year titers had dropped below this value in 18 (43%) infected compared with only 4 (11%) uninfected children (chi square, 9.7; P = 0.002). Although the rate of fall of antibody titer was greater in uninfected than in infected children, this was no longer the case after adjustment for the 1-month postimmunization titer. The rate of antibody titer decline was not significantly related to HIV disease status or to either the age-related CD4 count at the time of immunization or the change in age-adjusted CD4 count during the 12 months after immunization. CONCLUSIONS: Not only was the initial antibody response to Hib conjugate vaccine decreased in children with HIV infection and AIDS but also 1 year later only 57% of the initial responders had persisting titers above the level associated with long term protection. The need for reimmunization of children with HIV infection against Hib requires further evaluation.

Intracranial hypertension and cryptococcal meningitis in a girl with AIDS.

A girl with HIV infection acquired at birth by blood transfusion, was admitted at the age of 10 years for diplopia, vomiting, headache and papilledema. CT scan was negative. A lumbar puncture revealed clear CSF, protein 0.40 g/l, glucose 2 mmol/l, 5 mononuclear cells/mm3. The Indian ink preparation and the latex agglutination antigen test were positive for Cryptococcus n. Treatment with amphotericin B and flucytosine was started. After 10 days, since the in vitro susceptibility testing of the isolates showed resistence to both drugs, fluconazolo (400 mg/day) was started. Acetazolamide, furosemide and spironolactone were then added to the antifungal therapy for the persistence of severe intracranial hypertension. Diuretics were maintained for 10 weeks. The patient returned to school two and half months after the admission to the hospital. After 19 months, she is doing well and she is on maintenance of fluconazole (200 mg/day). We hypothesized that the increased intracranial pressure would be due to an impaired CSF reabsorption probably as a consequence of a direct cryptococcal infiltration of the villi.

Mode of delivery and gestational age influence perinatal HIV-1 transmission. Italian Register for HIV Infection in Children.

Some data suggest that cesarean section reduces mother-to-child HIV-1 transmission. To assess the influence of mode of delivery and other maternal and infant factors on the rate of transmission, we analyzed the data of 1,624 children prospectively followed from birth. Of these, at the last visit 1,033 were > 18 months of age or would have been had they not died of HIV-related illness. Among the 975 first singleton children, 180 [18.5%; 95% confidence limits (CL), 16.1-20.9] acquired infection, as did 8 of 56 (14.3%; 95% CL, 5.1-23.5) second-born children. Multivariate stepwise analysis showed that vaginal delivery and development of symptoms in the mother were significantly and independently associated with a higher transmission rate (vaginal delivery; odds ratio, 1.69; 95% CL, 1.14-2.5; symptoms: odds ratio, 1.61; 95% CL, 1.12-2.3). In contrast, a history of maternal drug use, birth weight, breast-feeding (only 37 infants were breast-fed), and child's sex did not have a significant impact on viral transmission. The percentage of infected children was highest (30.7%) among very premature infants (< or = 32 weeks of gestation); this significant trend subsequently decreased to 11.9% at the week 42 (p < 0.001), suggesting a parallel reduction in peripartum transmission. The reduced rate of infection observed in infants born by cesarean section underlines the urgent need for randomized controlled trials to evaluate the protective role of surgical delivery in preventing perinatal HIV-1 transmission.

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods. Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: (a) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels (> 1,000 HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; (b) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; (c) a significantly lower (> 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern. These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants.

Viral phenotype and host-cell susceptibility to HIV-1 infection as risk factors for mother-to-child HIV-1 transmission.

OBJECTIVE: To investigate the role of maternal HIV-1 isolate phenotype and a child's cell susceptibility/resistance to viral infection in mother-to-child HIV-1 transmission. PATIENTS AND METHODS: Forty-nine women were studied at the time of delivery. Primary isolates, obtained by culturing patient peripheral blood mononuclear cells (PBMC) with PBMC from healthy donors, were characterized for tropism and syncytium-inducing capability in monocyte-derived macrophages (MDM), peripheral blood lymphocytes (PBL), and in the MT-2 and MOLT-3 T-cell lines. RESULTS: Seven women transmitted HIV-1 to their children. Primary isolates were obtained from six and 28 transmitting and non-transmitting mothers, respectively. All primary isolates from transmitting mothers and their infants but only 50% of those from non-transmitting mothers replicated in MDM, regardless of their replication capacity in T-cell lines. PBL and MDM cells from six uninfected children were exposed to the corresponding maternal isolates. Polymerase chain reaction analysis of HIV-1 DNA in cells and p24 antigen assay in culture supernatants disclosed that two PBL and five MDM cultures were resistant to viral infection; two other PBL cultures, although HIV-1-infected, were negative for p24 production. Depletion of CD8+ cells only partially restored productive infection in CD4+ cell cultures. Moreover, all six PBL but only one MDM cultures were productively infected by an isolate obtained from a transmitting mother, thus suggesting that MDM resistance to HIV-1 infection is not viral isolate-restricted. CONCLUSIONS: Our findings strongly suggest that mother-to-child HIV-1 transmission is influenced by both monocyte-macrophage tropism of the maternal isolate and susceptibility of the child's target cells, in particular monocyte-macrophages, to HIV-1 infection.

The use of antibiotics in the treatment and prevention of infection in HIV-infected children.

Children with HIV infection have an unusual susceptibility to bacterial infection, related to several immune abnormalities. Selection of initial antibiotic therapy must be individualized in these children. Patients with community-acquired disease are most likely to have infection by polysaccharide-encapsulated bacterial organism, most commonly Streptococcus pneumoniae and less frequently by Haemophilus influenzae type b. If it is possible to treat the patients at home, the use of amoxicillin-clavulanic acid might be appropriate. Other authors propose management with parenteral ceftriaxone because of the better compliance and the malabsorption. In hospitalized patients, concern for Gram-negative enteric pathogens other than polysaccharide-encapsulated organisms requires initial therapy with a third-generation cephalosporine in combination with an aminoglycoside. Trimethoprim-sulfamethizole is the most common drug used in HIV-infected children because it is recommended for the initial therapy and for prophylaxis of pneumocystis carinii pneumonia, which occurs in as many as 42% of these children.

Paediatric AIDS: a new child abuse.

In relation to youth rights, a new view has been created in recent decades that is included in the fundamental law of the child: the recognition of the right to education and the chance to develop a mature personality capable of creativity and liberty. Because of HIV infection it is very important to pay particular attention to the rights of the seropositive child and children born to seropositive mothers, which may be hampered not only in developing countries but also in the industrial world. HIV-affected children and their families are becoming abused and at high risk of becoming abused and this encroaches upon youth rights. As a consequence, in 1991 the Italian Society of Paediatrics issued a "Charter for the rights of seropositive children", which became an important document for all health care and social workers who deal with HIV-affected children. In this paper, we also consider the impact of HIV infection on the three main rights of children: the right to live, the rights of security and the rights of socialization.

HIV-1 transmission through breast-milk: appraisal of risk according to duration of feeding.

OBJECTIVES: To estimate the risk of HIV-1 transmission through breast-milk in children born to infected mothers, and to determine the relationship between duration of breast-feeding and risk. DESIGN AND METHODS: The study population included 168 breast-fed and 793 bottle-fed children born to seropositive mothers. All subjects were enrolled and followed-up in the Italian Register for HIV Infection in Children; HIV sero-status was defined in all children. Multivariate analysis was performed using a logistic regression model. Independent variables included biological factors (duration of breast-feeding, gestational age, clinical condition of mother at delivery, mode of delivery, birth-weight and sex). Year of birth and age when HIV infection was diagnosed were also considered in the analysis attempting to control for possible selection biases. RESULTS: Breast-feeding increased the risk of HIV-1 transmission. The estimated adjusted odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence interval, 1.10-1.28). The infection odds ratio of breast- versus bottle-feeding increased with the natural logarithm of the duration of practice. CONCLUSIONS: These results are the first to provide an appraisal of the additional risk of HIV-1 transmission associated with a seropositive mother breast-feeding her child. Biological significance of this route of transmission was supported by demonstration of a relationship between duration of breast-feeding and risk of HIV-1 transmission.

How frequent and how early does the neurological involvement in HIV-positive children occur? Preliminary results of a prospective study.

To study the natural history of the neurological involvement in pediatric human immunodeficiency virus (HIV) infection, 77 children born to seropositive mothers have been followed up since birth. The median follow-up time has been 17.5 months. Fourteen children were classified as infected, 34 as not infected, and 21 as indeterminable. Only two children with full-blown acute immune deficiency syndrome had severe neurological manifestations. "Soft" neurological signs were found in six infected, and ten non-infected children (chi 2, P < 0.05). The mean development quotient and IQ scores in the infected and the non-infected children were 82.22, and 93.15, respectively (Mann-Whitney test, P > 0.05). These data suggest that neurological and developmental abnormalities do not occur early in the course of vertical HIV infection and that they are associated with severe immunodeficiency.