Evaluation and treatment of the human immunodeficiency virus-1--exposed infant

In developed countries, care and treatment are available for pregnant women and infants that can decrease the rate of perinatal human immunodeficiency virus type 1 (HIV-1) infection to 2% or less. The pediatrician has a key role in prevention of mother-to-child transmission of HIV-1 by identifying HIV-exposed infants whose mothers' HIV infection was not diagnosed before delivery, prescribing antiretroviral prophylaxis for these infants to decrease the risk of acquiring HIV-1 infection, and promoting avoidance of HIV-1 transmission through human milk. In addition, the pediatrician can provide care for HIV-exposed infants by monitoring them for early determination of HIV-1 infection status and for possible short- and long-term toxicities of antiretroviral exposure, providing chemoprophylaxis for Pneumocystis pneumonia, and supporting families living with HIV-1 infection by providing counseling to parents or caregivers.     

Italian guidelines for antiretroviral therapy in children with human immunodeficiency virus-type 1 infection. Italian Register for HIV Infection in Children

Human immunodeficiency virus-type 1 (HIV-1) infection and its treatment are peculiar in children. Adherence and compliance must be carefully taken into account before initiating or changing therapy and in the choice of drugs. Even in the absence of paediatric-specific trial results and notwithstanding drug-labelling notations, all antiretroviral drugs should be used when indicated. A combined therapy is compulsory. Therapy is highly recommended in category C or category 3 and recommended in category B children. Indications in categories N1, N2, A1 or A2 are limited. A triple association is recommended in category C or category 3 children or in those with a high viral load, when compliance is guaranteed. A step-down strategy is not advisable. Infants'treatment should be inserted into controlled studies. Therapy should be changed when serious side effects or poor tolerance (choose drugs with a different toxicity and greater tolerance), poor compliance (individualize the motives) or treatment failure (evaluate progression and adherence) occurs.     

Reduced frequency of wheezing respiratory illness in infants with perinatal human immunodeficiency virus-type 1 infection: A model for immunologic and inflammatory mechanisms of airway obstruction?

A multivariate analysis using a logistic regression model evaluated odds ratio (OR) and 95% confidence limits (95% CL) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 (HIV-1) infection, 205 uninfected infants of HIV-1 infected mothers, and 1780 infants of HIV-1 uninfected mothers. Infants were prospectively followed-up for the first 2 years of life. Covariates were risk factors for wheezing respiratory illness (preterm delivery, low birth weight, maternal smoking, formula feeding, and neonatal respiratory disorders). Maternal use of illicit drugs in pregnancy, antiretroviral treatment in pregnancy, maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account. Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers, HIV-1 infection emerged as a protective factor [OR: 0.001 (95% CL: 0.0001–0.01); p < 0.001]. The frequency of risk factors was similarly high among infants of infected mothers, but OR was lower in HIV-1 infected than in uninfected infants of infected mothers (0.005; 95% CL: 0.0004–0.06; p < 0.001). Finally, OR was higher in uninfected infants of HIV-1 infected mothers (who evidenced a higher frequency of risk factors) than in infants of HIV-1 uninfected mothers (9.97; 95% CL: 4.87–20.40; p < 0.001). Understanding the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction.     

Early detection of IgA specific antibodies in HIV-1 infected children by peptide-ELISA and peptide time-resolved fluoro-immunoassay

The presence of specific IgA antibodies in sera from 25 infants born to HIV-1 seropositive mothers was investigated by peptide-ELISA and peptide time-resolved fluoro-immunoassay (TR-FIA). The infants had been monitored at different times after birth for clinical signs and/or symptoms of HIV-1 infection and for detection of HIV-1 in lymphocyte cultures. Serum samples had also been tested for HIV-1 IgG antibodies by commercial ELISA and Western blot and for p24 antigen. Eleven of 25 children were then identified as infected. IgA detection was performed after rProtein G treatment to remove interfering IgG. In the infected group, IgA specific antibodies to a synthetic peptide representing a highly conserved region of the transmembrane glycoprotein gp41 (env: 594–613) were detected in 27 (73%) out of 37 serum samples (9 of 11 children) by the peptide-ELISA test. IgA specific antibodies to the same peptide were found in 30 (81%) sera (9 of 11 children) by the peptide-TR-FIA. Specific HIV-1 IgA antibodies were detected as early as 2 months of age in serum samples from five out of seven children (71% sensitivity) using peptide-ELISA and from six out of seven (86% sensitivity) by peptide-TR-FIA. Conversely, IgA specific antibodies to HIV-1 were absent in two infected children as well as in the sera of all uninfected children tested during the follow up period. Since maternal IgA does not cross the placenta, IgA detection in the serum of the infant is indicative of HIV-1 infection. Indeed, the early demonstration of HIV-1 IgA antibodies in infected infants shows that both peptide-ELISA and peptide-TR-FIA can be used for an early diagnosis of HIV-1 infection.     

Dynamics of progression markers in a non-study population of human immunodeficiency virus-1 vertically infected infants with different antiretroviral treatments

Treatment with highly active antiretroviral therapy (HAART) has been shown to modify viral replication dynamics and lead to a significant recovery of CD4 + T-cells. A retrospective multicentre observational study was performed in a non-study population of 151 HIV-1-infected children, categorized into four groups according to therapy: untreated (NT), on monotherapy (MT) with a nucleoside inhibitor, on combination therapy (CT) with two nucleoside inhibitors, and on HAART, protease inhibitor containing regimens, to assess the "real-life" effectiveness of these different therapies on plasma viral load (VL) and CD4 + T-cells. VL was quantified using a standard molecular assay. CD4 + and CD8 + T-cells subsets were determined by flow cytometry. The HAART group showed the highest relative proportion (RP) of increases in 5, 10, 15 and 20% of CD4 + T-cells over baseline, and the earliest fall-off of VL (0.5, 1, 1.5 and 2 log 10 copies ml -1 ). The RP of the fall-off of 0.5, 1, 1.5 and 2 log 10 VL below baseline was 3-fold higher in HAART group than in the MT and CT groups. However, no differences were found among the groups of treated children in reaching undetectable VL.

Conclusion: A better evolution of VL and CD4 + T-cells was evident in children on HAART, indicating a positive effect on the immune system and clinical status, inhibiting HIV-1 replication and enabling the recovery of CD4 + T-cell counts.     

Vertical human immunodeficiency virus-1 infection: Involvement of the central nervous system and treatment

Involvement of the central nervous system (CNS) contributes substantially to morbidity and mortality of vertical infection with the human immunodeficiency virus (HIV)-1. The clinical spectrum ranges from minor developmental disabilities to severe and progressive encephalopathy. Progression of the disease varies considerably. Both direct viral and indirect host-related pathogenic mechanisms have been proposed. The diagnosis depends on neurological and neurodevelopmental assessments. So far, HIV-1-specific antiviral treatment has shown limited effects on neurological manifestations in symptomatic children. Thus, efforts are needed to improve prevention and treatment of CNS involvement. It is still unclear whether early use of antiretroviral agents is of benefit. Conclusion Since experience of treatment of HIV-1 infections in adults cannot easily be translated to children, paediatric clinical trials are needed to answer questions specific to the unique characteristics of children. Received: 10 March 1996ƒAccepted: 10 May 1996     

Impact of infant feeding practices on the risk of mother to child transmission of HIV-1 in Zimbabwe

OBJECTIVE: To determine the magnitude of the contribution of infant feeding practices on the risk of mother to child transmission (MTCT) of the HIV-1 infection. METHODOLOGY: Prospective data from birth until 24 months of age on 236 infants born to HIV-positive mothers in Harare, Zimbabwe was analysed for this study. However, because only a small proportion of infants (2.1%) were HIV-1 polymerase chain reaction (PCR) tested shortly after birth, the PCR results for infants at birth were not incorporated into our analyses. The contribution of infant feeding practices on the risk of MTCT of HIV-1 was assessed using Cox Proportional Hazards Regression Models. RESULTS: The incidence of HIV-1 through MTCT was greatest among breastfed (8.33 per 100 child-months) and mixed fed (8.64 per 100 child-months) infants by 3 months. After adjustment for maternal age, marital status, education and infant antibody HIV-1 status, the cumulative relative risk of MTCT of HIV-1 was 4.19 (95% confidence interval (CI) 3.44, 5.09) among breastfed and 1.10 (95% CI 0.97, 1. 25) among mixed fed infants. The overall MTCT rate of HIV-1 in this study was 40.3%. CONCLUSIONS: Breastfed infants had the greatest cumulative relative risk of MTCT of HIV-1, followed by mixed fed infants, with the highest incidences occurring within the first 3 months.     

Breast-feeding and human immunodeficiency virus

Breast-feeding provides nutritional, immunological, and psychological benefits. It protects children from mortality and morbidity associated with diarrheal diseases, pneumonia and other infections. Breast feeding has also been shown to prolong the interval between births and thereby improve child survival and maternal health. However, studies suggest that in certain populations, breast feeding may account for nearly 14% of perinatal human immunodeficiency virus type 1 (HIV-1) transmission. It is therefore important that the risk of HIV-1 infection through breast feeding be weighed against the morbidity and mortality associated with bottle feeding. This paper discusses the literature dealing with breast feeding in women with HIV-1 infection. Specifically, the review addresses the issues surrounding infant mortality in areas of different HIV-1 prevalence where breast-feeding or bottle-feeding may be employed. Analysis suggests that the benefits of breast-feeding or bottle-feeding may be employed. Analysis suggests that the benefits of breastfeeding can substantially outweigh the putative risk of HIV-1 transmission unless the prevalence of HIV-1 infection is high or the difference in mortality between breast-fed and bottle-fed infants is very low.     

Rate of mother to child transmission of HIV and factors associated among HIV exposed infants in Oromia Regional State,Ethiopia: Retrospective study

Background

Mother to Child Transmission of HIV (MTCTH) is a major public health challenge in Ethiopia. Monitoring and evaluation of the rate of HIV transmission among infants born to HIV positive mothers is the major indicator to understand the performance of a national HIV control program. However, this is not well documented in Oromia Regional State, Ethiopia.

Human Immunodeficiency Virus type 1 infection and breast milk

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV-1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose-response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast-feeding was considered as the level of exposure in 168 ever breastfed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast- versus exclusive formula-feeding was 1.19 with narrow confidence limits (1.10–1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03–6.37) was calculated in breast- versus exclusively formula-fed children. Several lines of evidence, including the above-mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast-feeding to mother-to-child HIV-1 transmission. Thus, this practice is now discouraged in HIV-1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV-1 infected mothers since 1981. It could be observed that feeding habits of at-risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth. However, women infected exclusively by the sexual route are often unconscious of being infected or even being at risk from infection and consequently their children are less frequently identified at birth than are children of women with a history of intravenous drug use. In industrialized areas, the former children remain at risk from milk-borne HIV-1 infection.     

Current guidelines for the management of UK Infants born to HIV-1 infected mothers

Transmission of the Human Immunodeficiency Virus type 1 (HIV-1) from mother to child has been associated with maternal plasma viral load and CD4 lymphocyte count, prematurity, the mode of infant delivery, length of rupture of membranes and breast feeding. Without intervention, the transmission of HIV-1 occurs in a quarter to a third of infants born to infected mothers. During the last decade, mother-to-child transmission of HIV-1 has been reduced to less than 1%, through formula feeding, prelabour Caesarean section (PLCS) and antiretroviral therapy. With such an impressive reduction in the transmission of HIV-1, attention is turning towards the minimisation of possible drug side effects both in mothers and their infants. HIV-1-infected women are increasingly choosing to conceive on combination antiretroviral therapy, hence, infants are exposed to increasing numbers, combinations and classes of drugs, often from conception. Current guidelines on the prevention of mother to child transmission of HIV-1 are discussed.     

Cytomegalovirus esophagitis in a child with human immunodeficiency virus-1 infection presenting as fever of unknown origin and stunted growth

We report a 12-year old boy with human immunodeficiency virus-1 infection and cytomegalovirus-associated esophagitis, who presented with an indolent clinical course associated with fever of an unknown origin, failure to thrive and weight loss.     

Mother-to-child HIV-1 transmission: Quantitative assessment of viral burden as a diagnostic tool and prognostic parameter in HIV-1-infected children

Polymerase chain reaction was performed in 251 infants born to HIV-1-seropositive mothers to diagnose HIV-1 infection. Assay specificity was invariably > 95%, regardless of age at testing, while sensitivity ranged from 15% in neonates (within 48 h of birth) to > 95% in infants over 1 month of age. Evaluation of viral burden in 43 infected infants by means of quantitative DNA-PCR disclosed that the number of HIV-1 proviruses ranged from 5 to 947 per 100,000 peripheral blood mononuclear cells. Clinical follow-up demonstrated that a high viral burden was associated significantly with disease onset.     

Feeding practices of HIV-1-infected mothers: the role of counsellors

In this issue of Acta Paediatrica, Chopra et al. report that voluntary counselling is central to preparing mothers for making a proper informed choice about adequate feeding practices to prevent their infants from acquiring HIV infection. The recommendations given and the way in which counselling is performed are the most important determinants of a mother's decision about how to feed her infant. In this article, we summarize the main arguments for and against breastfeeding by HIV-infected mothers. Conclusions: Further studies are needed to determine the alternatives to breastfeeding in countries where there is no access to safe formula feeding or to antiretroviral drugs. HIV-positive mothers should be made aware of the available feeding alternatives through adequate counselling from properly trained persons.     

Anthropometric indicators of human immunodeficiency virus infection in infants with early and late symptoms in the first months of life

Standardised growth indices (Z-scores of weight-for-age, WA, length-for-age, LA, weight-for-length, WL, according to the reference data of the World Health Organization) have been compared for the first 4 months of life among 119 infants born to mothers affected by the type-1 human immunodeficiency virus (HIV). Infants were subdivided according to their HIV serostatus and the clinical expression of the disease. Uninfected status (n = 92), late (≥6 months, n = 18) and early (≤3 months, n = 9) onset of symptoms among the HIV infected defined three groups. Infants with early symptoms showed the lowest median WA and LA Z-scores at all times and the LA difference with their uninfected counterparts was already significant at birth. Infants with late symptoms showed early differences in WL and then in WA also compared with the uninfected ones. A<−0.40 LA Z-score at birth gave a 5.9 relative risk (RR) to be an infant with early symptoms (95% CI = 1.2−27.4) while a negative WL Z-score at 2 months of age gave a 4.2 RR for the HIV seropositivity (95% CI = 2.1−8.3). Conclusion Linear growth is the first parameter to be negatively affected among human immunodeficiency virus seropositive infants with early symptoms. In infants with late symptoms the lack of rapid WA and WL increase found among uninfected patients may be viewed as an early anthropometric indicator of HIV status. Received: 12 January 1998 / Accepted: 2 February 1998