G. Ferraris

Increased Risk of Maternal-Infant Hepatitis C Virus Transmission for Women Coinfected with Human Immunodeficiency Virus Type 1

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.

Features of children perinatally infected with HIV-1 surviving longer than 5 years. Italian Register for HIV Infection in Children

Children infected with HIV do not necessarily develop AIDS to a set pattern but can be divided into long-term and short-term survivors. We examined long-term survival in children perinatally infected with HIV-1. Out of a total of 624, we studied 182 children who survived longer than 5 years (long-term survivors [LTS]) and 120 children who died of HIV-1-related disease before 5 years (defined as short-term survivors [STS]). 28 (15%) LTS were symptomless (Centers for Disease Control [CDC] P-1 children). 154 (85%) had symptoms (CDC P-2). The proportion of LTS with less than 0.2 x 10(9)/CD4 cells per L was 24/116 (21%) at 61-72 months, rising to 11/26 (41%) at more than 96 months. On at least one occasion, p24 antigenaemia was observed in 112 (62%) LTS. Annual rate of CD4 cell loss was lower in LTS (25% [95% CI: 21-29]) than in STS (53% [45-60]) and in LTS symptomless or with solitary P-2A signs (17%; [13-21]) than in LTS with severe manifestations (30% [25-35]). A new outlook emerges. A substantial number of children do survive after early childhood; severe diseases; low CD4 cell numbers, and p24 antigenaemia do not necessarily preclude long-term survival. The study shows that a CD4 cell decrease early in life can be predictive of outcome.

Polymerase chain reaction, virus isolation and antigen assay in HIV-1-antibody-positive mothers and their children

Diagnosis of perinatal HIV-1 infection is complicated by the persistence of maternal antibodies and the conflicting reports on polymerase chain reaction (PCR) reactivity in children born to HIV-1-seropositive mothers. We have compared PCR with other diagnostic methods for perinatal HIV-1 infection and have attempted also to identify maternal markers which correlate with risk of transmission. PCR was the most sensitive method for early diagnosis of perinatal transmission of HIV-1, but the PCR-positive children (n = 11) developed at least one additional sign of infection. The PCR-negative children (n = 76) were clinically healthy, virus isolation negative, and their serum was HIV-1-antigen-negative. All children who had become seronegative (n = 36) were both PCR- and isolation-negative. Antigenaemia in the mothers correlated significantly with higher risk of perinatal transmission of HIV-1, while no other parameters (clinical stage, lymphocyte subsets, PCR and isolation) showed such a correlation. This indicates that the level of virus expression may be of key importance for the risk of vertical transmission of HIV-1 infection.

Features of children perinatally infected with HIV‐1 surviving longer than 5 years

ly surveillance for the occurrence of diarrhea. Stool specimens collected at the onset of diarrhea were evaluated for enteropathogens. Infants who were infected with HIV were compared with uninfected infants. Subjects: Infants born to HIV-infected women at the University of Maryland Hospital, Baltimore, were recruited at 0 to 3 months of age. This analysis included 58 infants enrolled in the cohort and followed up at least 15 months (unless death intervened) whose HIV status was established (18 HIV-infected infants and 40 HIVuninfected infants). Measurements and Results: The overall incidence of diarrhea in HIV-infected infants was 3.2 episodes per 12 child-months compared with 1.5 episodes per 12 childmonths among HIV-uninfected infants (incidence density ratio, 2.2; P < 0.05). An enteropathogen was identified in stool specimens collected during 20% of diarrhea1 episodes occurring in HIV-infected infants and during 25% of diarrhea1 episodes occurring in HIV-uninfected infants. Episodes that persisted for 14 days or longer were significantly more common among HIV-infected infants. The peak incidence of diarrhea occurred at 0 to 5 months of age for HIV-infected infants compared with 6 to 1 I months for HIV-uninfected infants. Early onset of diarrhea (< 6 months old) in HIV-infected infants was associated with the later development of persistent episodes of diarrhea, and those with persistent episodes had more severe HIV infection, characterized by a significantly higher frequency of opportunistic infections and lower CD4+ T lymphocyte counts by 1 year of age. Conclusions: Both acute and persistent episodes of diarrhea are major sources of morbidity in HIVinfected infants. Moreover, persistent diarrhea is a marker for rapid progression of HIV disease.

Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy The Italian Register for HIV Infection in Children*

OBJECTIVE To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine (ZDV) monotherapy in pregnancy. DESIGN Observational retrospective study of a prospectively recruited cohort. SETTING Italian Register for HIV Infection in Children. PATIENTS A group of 216 children perinatally infected with HIV-1, born in 1992-1997 and derived prospectively from birth: 38 children had mothers receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy. MAIN OUTCOME MEASURES The estimated probability of developing severe disease or severe immune suppression, survival probability [95% confidence interval (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatments (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral therapy before the onset of severe disease, severe immune suppression or death) were compared. RESULTS Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [57.3% (95% CI 40.9-74.3) versus 37.2% (95% CI 30.0-45.4); log-rank test 7.83, P = 0.005; adjusted hazard ratio 1.8 (95% CI 1.1-3.1)] or severe immune suppression [53.9% (95% CI 36.3-73.5) versus 37.5% (95% CI 30.0-46.2); log-rank test 5.58, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower survival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank test 4.23, P = 0.039; adjusted hazard ratio of death 1.9 (95% CI 1.1-3.6)]. CONCLUSIONS This epidemiological observation could stimulate virologic studies to elucidate whether this rapid progression depends on in utero infection or transmission of resistant virus. Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected.

Immunization in children with HIV seropositivity at birth : antibody response to polio vaccine and tetanus toxoid

ObjectiveTo evaluate the humoral response to routine childhood immunization of HIV-infected children. DesignResponse rate, antibody titres and persistence after polio and tetanus vaccination were compared in 72 children with HIV seropositivity at birth and divided according to HIV infection status as determined by clinical and laboratory tests. MethodsPolio antibodies were titred in a microneutralization test (positive titres, ≥1:4), and antibody to tetanus toxoid with a passive haemagglutination method (protective titres, ≥1:1024). ResultsThe response rates to polio and tetanus vaccination (>80 and >75%) were similar in the HIV-infected and non-infected children, as were antibody levels. In the subgroup with sera obtained some months after the last dose of vaccine, polio antibody levels decreased in all four HIV-infected and in three of the seven non-infected children; protective tetanus antitoxin levels were detected in three of the six infected and in all three non-infected children. ConclusionsThis study demonstrates the ability of children with HIV infection to respond adequately to the two vaccines considered, although tetanus antitoxin levels were inferior, compared with those in the seroreverted children. The unsatisfactory antibody levels observed in the admittedly few HIV-positive children studied some months after the last vaccination could be the result of a lower initial protective level and not necessarily an expression of severely impaired immunocompetence. The administration of booster doses in addition to the traditional immunization schedule could be useful in children with HIV infection.

Pregnancy outcome among HIV positive and negative intravenous drug users

OBJECTIVE To analyze determinants of pregnancy outcome, among HIV infected and uninfected intravenous drug users. STUDY DESIGN A total of 315 pregnant current intravenous drug users, IVDU (151 HIV infected and 164 HIV uninfected subjects) were referred to the Center for Pregnant Drug Addicts of the Mangiagalli Clinic, Milan, Italy, for internatal care and delivery between 1985 and 1993. RESULTS HIV uninfected and infected mothers did not differ significantly according to type of pregnancy, gestational age at childbirth, mode of delivery, pregnancy outcome and newborn weight, height, head circumference, sex and Apgar at 1 and 5 min. Out of 133 children (born to HIV infected mothers) for whom HIV status was available, 20 (15%) were HIV infected or developed AIDS-related signs and symptoms during a 24 months follow-up. The distribution of HIV infected and non infected infants was not significantly different as regards maternal CD4 lymphocyte count, week of gestation at birth, mode of delivery, infant weight, height, head circumference and Apgar at 1 and 5 min. CONCLUSION Our data show that HIV infected women in the early stages of HIV infection are not at a higher risk of adverse course of pregnancy than HIV uninfected women. Vertical transmission rates were not associated to newborn characteristics.

Fatty acid composition of plasma lipids in HIV-infected children. Comparison with seroreverters.

Children infected with the type‐1 human immunodeficiency virus (HIV) are at risk of nutritional deficiencies leading to an impaired polyunsaturated fatty acid (PUFA) status. The aim of the present study was to compare the PUFA composition of plasma lipid classes (total lipids, phospholipids (PL), cholesteryl esters (CE) and triglycerides) in well‐growing HIV‐infected children with an age‐matched group of HIV‐seroreverter children born to infected mothers. Eighteen HIV children, of both sexes, mean age 4.6 y, most of whom under combined antiretroviral regimen, were compared with 18 seroreverters, mean age 5.4 y, comparable for demographic, anthropometric and dietary characteristics. All children had adequate growth parameters (weight and height>3rd percentile). The plasma fatty acid content was similar in the two groups. HIV seropositive subjects showed lower linoleic acid (LA) levels in all the plasma lipid fractions, with higher 20:3n‐9 and 20:5n‐3 levels in PL and CE. The plasma PL triene/ tetraene ratio (marker of relative LA deficiency) related positively to the viral load and negatively to the blood CD4+ lymphocyte count. Compared to age‐matched seroreverter subjects, HIV‐seropositive children show a lipid fatty acid status suggestive of relative LA deficiency and increased turnover of the PUFA series.

Humoral Response to Inactivated Poliovaccine in Anti-HIV Positive Infants

The growing number of paediatric immune deficiency virus ( HIV ) infections has raised some problems about the appropriate policies for vaccinations. Some aspects must especially be pointed out: 1) the possible severe side—effects as well as disseminated infection caused by live vaccines in immunodeficient subjects; 2) the excessive stimulation of T Lymphocytes by both live and inactivated vaccines, with the possibility to accelerate the course of HIV infection; 3) the capacity of HIV-infected children to respond properly to immunisation; 4) the course of vaccine-preventable-diseases in HIV-infected children.

Low Prevalence of Selective IgA Deficiency in Infected Children Born to HIV-Seropositive Mothers: An In Vivo Model for Speculation on Selective IgA Deficiency Pathogenesis

Anecdotal reports of restored immunoglobulin production in individuals with common variable immunodeficiency after acquiring HIV infection suggest that perturbation of the immune system occurring during HIV infection may force some underlying functional defects. These findings raise intriguing questions about the pathogenesis of common variable immunodeficiency. No study has investigated the possible influence of HIV infection on the development of selective IgA deficiency, a primary immunologic defect genetically related to common variable immunodeficiency. IgA serum levels were evaluated in a large cohort of children born to HIV-infected mothers from 1985 to 2006. To avoid differences possibly due to different follow-up durations we considered only infected and non-infected children aged over 4 years at last-follow-up. The study included 1,157 non-infected children and 964 infected children, aged ≥ 4 years at last-follow-up and with availability of two or more serum IgA determinations over six months of age. No child displayed immunoglobulin values compatible with diagnosis of common variable immunodeficiency. However, 0/964 infected children vs. 5/1157 non-infected children had selective IgA deficiency (P=0.048). It may be speculated that several immunological alterations, occurring simultaneously in perinatal HIV infection, surpass the functional defect exhibited in some children with selective IgA deficiency. Our data may shed light on the pathogenesis of selective IgA deficiency.