Effectiveness of early initiation of protease inhibitor-sparing antiretroviral regimen in human immunodeficiency virus-1 vertically infected infants.

Each of the 17 vertically infected infants born to HIV-1-infected mothers in Belgian HIV reference centers since 1996 was treated with a combination of 3 reverse transcription inhibitors as soon as the diagnosis was established. Treatment was initiated in all patients before 66 days of life. Twelve patients, including 11/13 infants treated with the combination of zidovudine, lamivudine and nevirapine, experienced a complete viral suppression (<50 copies/mL) with their first drug regimen. At last follow-up, 12 patients were asymptomatic, 2 were CDC stage A and 3 were stage B; 15 had HIV-1 RNA levels of <50 copies/mL and 14 had >or=25% CD4 lymphocytes. These results suggest that early initiation of treatment with 3 reverse transcription inhibitors is highly effective to inhibit viral replication and to prevent clinical and immunologic progression of HIV infection in vertically infected infants.

Efavirenz in human breast milk, mothers', and newborns' plasma.

BACKGROUND AND METHODS: Highly active antiretroviral therapy with efavirenz (EFV) has been prescribed to HIV-positive pregnant women in Rwanda (HIV status 1 and CD4 cell count > 350 cells/mm) during the last trimester of pregnancy and for 6 months after delivery. The EFV concentrations in maternal plasma, breast milk and in newborns' plasma of 13 women and their children between 6 weeks and 6 months post partum are reported. RESULTS: Results show a mean EFV plasma concentration of 6.55 mg/L in maternal plasma, 3.51 mg/L in skim milk, and 0.85 mg/L in infant plasma. Significant linear correlations between maternal plasma and skim milk (r = 0.8666, P < 0.0001) and between skim milk and infant plasma (r = 0.6646, P < 0.02) were found, but no significant correlation was observed between maternal and infant plasma concentrations (P > 0.05). CONCLUSIONS: After 6 months of breast-feeding, no child out of the 13 had been infected with HIV and all had good psychomotor and growth development. Our results suggest that EFV may be an alternative to nevirapine (NVP) during the third trimester of pregnancy and during the breast-feeding period. Further studies on larger groups of newborns will be necessary to get a better understanding of possible prophylactic protection of the newborns by highly active antiretroviral therapy with EFV given to the mothers.

Adolescents and HIV infection.

PURPOSE OF REVIEW: Adolescence is defined by the WHO as the period of life between 10 and 20 years of age. Following the introduction of highly active antiretroviral therapy mortality from perinatally acquired HIV has fallen dramatically with children in the developed world increasingly surviving into adolescence and adult life. Teenagers growing up with HIV/AIDS have common problems related to social difficulties and to side effects of HIV and highly active antiretroviral therapy impacting on their growth and development. RECENT FINDINGS: They start their sexual life with the very difficult challenges of HIV in relation to sex and stigmatization. Adolescents with HIV are at risk of infecting partners and children in case of pregnancy and of acquiring additional sexually transmitted infections themselves. Adherence is often not very good at this time of life and disclosure, support group and practical help will reduce virological failure and resistance mutations to highly active antiretroviral therapy. CONCLUSION: Pediatric materials exist for early disclosure to prepare infected children for adolescence. Within a multidisciplinary team we have to be ready to take care of teenagers and to prepare children for the period of transition that culminates in the transfer to adult services.

Prevalence of lipodystrophy in HIV-infected children: a cross-sectional study.

OBJECTIVE: The aim of this study was to assess the changes in body fat distribution and lipid abnormalities in a population of HIV-infected children and adolescents followed in one single centre who had been exposed, or not, to antiretroviral therapy (ART). MATERIALS AND METHODS: Patients aged between 3 and 19 years were evaluated in a cross-sectional study carried out between October and December 2002. Fat redistribution was evaluated independently by the physician and the patient. Fasting blood lipid profile, glucose, insulin and C peptide were measured. Among the 88 patients evaluated, 74 were taking ART. RESULTS: Fat redistribution was present in 20 patients, metabolic alterations alone were found in 22 children and 46 children had neither physical nor metabolic abnormalities. Patients with fat redistribution were found to have been on ART for a significantly longer period of time, with 42% of the children showing fat redistribution having been treated with antiretroviral agents for more than 5 years. These children had also been exposed to a higher number of antiretroviral agents. In contrast, metabolic alterations in the absence of fat redistribution were not related to the duration of ART nor to the number of drugs received. Treatment with stavudine or protease inhibitors was significantly associated with the presence of physical changes. CONCLUSION: Regular assessment of fat redistribution and metabolic markers should be carried out in children treated with antiretroviral agents and taken into account when adapting therapy during the long-term follow up of these children.

Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses.

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.

Older children and adolescents surviving with vertically acquired HIV infection.

This article describes the characteristics of children infected vertically with HIV surviving 10 years or more who were enrolled in the prospective European Collaborative Study. Thirty-four of 187 infected children were identified with a median age of 11.4 years (range, 10.1-15.9 years). Factors examined included clinical status, immunologic and virologic characteristics, type of antiretroviral therapy, and psychosocial characteristics. By 10 years of age, 6 (18%) children had progressed to Class A as determined by the system of the U.S. Centers for Disease Control and Prevention (CDC), 17 (52%) to class B, 7 (21%) to class C, and 3 (9%) had remained asymptomatic. At 73% (904 of 1234) of scheduled clinic visits, these children had no symptoms of HIV disease. Most children were in CDC immune categories 1 (18, 56%) or 2 (11, 34%) at their last visit. Three quarters (24 patients) were on combination therapy with three or more drugs, although 3 children had never received any antiretroviral therapy. Nineteen (56%) children were living with at least 1 parent and the mothers of 13 (38%) children had died. Most (77%) children had been told about their HIV infection. Children infected vertically with HIV who have survived their first 10 years are mainly free of serious symptoms. As they enter adolescence, additional services are needed including support with disclosure to others, therapy, and sexual health.