International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection

doi:10.1016/S0140-6736(98)01419-6

The Lancet

Volume 352, Issue 9128, 22 August 1998, Pages 597-600

https://doi.org/10.1016/S0140-6736(98)01419-6 Get rights and content

Summary

Background

An understanding of the risk and timing of mother-to-child transmission of HIV-1 in the postnatal period is important for the development of public-health strategies. We aimed to estimate the rate and timing of late postnatal transmission of HIV-1.

Methods

We did an international multicentre pooled analysis of individual data from prospective cohort studies of children followed-up from birth born to HIV-1-infected mothers. We enrolled all uninfected children confirmed by HIV-1-DNA PCR, HIV-1 serology, or both. Late postnatal transmission was taken to have occurred if a child later became infected. We calculated duration of follow-up for non-infected children from the time of negative diagnosis to the date of the last laboratory follow-up, or for infected children to the mid-point between the date of last negative and first positive results. We stratified the analysis for breastfeeding.

Findings

Less than 5% of the 2807 children in four studies from industrialised countries (USA, Switzerland, France, and Europe) were breastfed and no HIV-1 infection was diagnosed. By contrast, late postnatal transmission occurred in 49 (5%) of 902 children in four cohorts from developing countries, in which breastfeeding was the norm (Rwanda [Butare and Kigali], Ivory Coast, Kenya), with an overall estimated risk of 3·2 per 100 child-years of breastfeeding follow-up (95% CI 3·1–3·8), with similar estimates in individual studies (p=0·10). Exact information on timing of infection and duration of breastfeeding was available for 20 of the 49 children with late postnatal transmission. We took transmission to have occurred midway between last negative and first positive HIV-1 tests. If breastfeeding had stopped at age 4 months transmission would have occurred in no infants, and in three if it had stopped at 6 months.

Interpretation

Risk of late postnatal transmission is consistently shown to be substantial for breastfed children born to HIV-1-positive mothers. This risk should be balanced against the effect of early weaning on infant mortality and morbidity and maternal fertility.

Introduction

Mother-to-child transmission of HIV-1 infection can occur during pregnancy in the intrapartum period or postnatally.¹ HIV-1 DNA is present in breastmilk² and postnatal transmission can occur through breastfeeding.3, 4 Breastfed children have a higher risk of mother-to-child transmission than those who have never been breastfed,⁵ and prospective follow-up of children born to HIV-1-infected mothers has shown that some infants become infected postnatally after loss of maternal antibodies.6, 7

Avoidance of breastfeeding by HIV-1-infected women is recommended if safe and affordable alternatives are available,⁸ a practice reinforced by WHO, UNICEF, and UNAIDS (UNAIDS website [HIV and infant feeding http://coww.unaids.org/unaids/document/epidemic/infant.html] accessed on July 28, 1998). In many developing countries, however, high expense and rates of infant morbidity and mortality are associated with alternative feeding methods and identification of HIV-1-infected pregnant women. In places where the prevalence of HIV-1 is high, postnatal acquisition of HIV-1 infection through breastfeeding remains a concern and a possible compromise would be to stop breastfeeding early.8, 9, 10

Although breastfeeding has been estimated to double the risk of vertical transmission,⁴ the exact risk and timing of transmission attributable to breastfeeding remain unclear. A randomised controlled trial of breastfeeding compared with bottle feeding is underway in Nairobi, Kenya,² which should provide a reliable estimate of the additional risk of HIV-1 transmission attributable to breastfeeding. The postnatal transmission risk of HIV-1 can also be assessed in large prospective studies with frequent laboratory followup of children born to HIV-1-infected mothers, in which postnatal transmission can be distinguished from intrapartum transmission.¹¹ In such studies, late seroconversions in breastfed children have been reported,6, 7, 12, 13, 14, 15 but the reliability of risk estimates needs to be improved.

Improved understanding of the risk and timing of postnatal transmission of HIV-1 is important for the development of strategies for infant-feeding and weaning policies.9, 16 Such understanding is especially relevant to interventions to decrease vertical transmission that are currently being developed and assessed.17, 18 We did an international multicentre pooled analysis to estimate the rate and timing of late postnatal transmission of HIV-1.

Section snippets

Methods

We gathered all published and unpublished data from completed or continuing cohort studies, in which information was available on sequential prospective laboratory follow-up (PCR, ELISA, and western blot) of children born to mothers known to be infected with HIV-1 before or at delivery. To limit the publication bias inherent to pooled analysis,¹⁹ we contacted all potential investigators through the International Working Group on Mother-To-Child Transmission of HIV-1, a large network of

Results

By October, 1997, we had gathered individual data from six cohort studies, and summary data from two other studies, including 5997 children (Table 17, 12, 14, 24, 25, 26, 27, 28). In the four cohorts from industrialised countries, 5% or less of children were ever breastfed, and laboratory follow-up included HIV-1 serology, DNA PCR, and viral culture every 3 months after birth. In the four developing-country cohorts, breastfeeding was the norm and, with the exception of Butare where only

Discussion

The previously reported risks of late postnatal transmission of HIV-1 infection were based on small numbers and ranged from 5% to 12%,11, 14 or a yearly incidence of 5·8 per 100 child-years of breastfeeding.¹² A study in Nairobi, Kenya, reported 40 cases of acquisition of infection though breastfeeding in children of mothers with either prevalent or incident HIV-1 infection.²⁴ We attempted to overcome difficulties of differences in definition of late postnatal transmission, laboratory methods

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This represents a first step towards the development of general immuno-epidemiological model frameworks of HIV exposure through breastfeeding and HIV persistence at the population level. There is strong evidence that the longer the duration of breastfeeding, the greater the risk of HIV transmission, i.e. the risk is cumulative (see Leroy et al. (1998); Miotti et al. (1999); Breastfeeding and HIV International Transmission Study Group et al. (2004)) with the cumulative risk of transmission through breastfeeding being 10–14% for infants aged 4–6 weeks and 22% for infants aged 18–24 months (Leroy et al. (2002); Nduati et al. (2000); The Petra study team (2002)). Several research teams have successfully designed experiments which confirm this hypothesis (see, for example, Hessell et al. (2009); Kersh et al. (2009); Van Rompay et al. (2005)).
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The past decade has seen marked improvements in the prevention and treatment of human immunodeficiency virus (HIV)/AIDS in pregnant women and children, yet significant mother-to-child transmission continues, disproportionately burdening resource-poor settings. Key areas of progress include (1) more aggressive prevention regimens for HIV-positive pregnant women including universal antiretroviral therapy (ART), (2) greater access to early testing for HIV-exposed infants, and (3) recommendations for universal ART for HIV-positive infants. This article addresses the prevention of HIV transmission to infants born to HIV-positive mothers, the care and treatment of children and adolescents infected with HIV, and the risks of HIV infection among adolescents.
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The prevalence of breastfeeding in France is one of the lowest in Europe: 65% of infants born in France in 2010 were breastfed when leaving the maternity ward. Exclusive breastfeeding allows normal growth until at least 6 months of age, and can be prolonged until the age of 2 years or more, provided that complementary feeding is started after 6 months. Breast milk contains hormones, growth factors, cytokines, immunocompetent cells, etc., and has many biological properties. The composition of breast milk is influenced by gestational and postnatal age, as well as by the moment of the feed. Breastfeeding is associated with slightly enhanced performance on tests of cognitive development. Exclusive breastfeeding for at least 3 months is associated with a lower incidence and severity of diarrhoea, otitis media and respiratory infection. Exclusive breastfeeding for at least 4 months is associated with a lower incidence of allergic disease (asthma, atopic dermatitis) during the first 2 to 3 years of life in at-risk infants (infants with at least one first-degree relative presenting with allergy). Breastfeeding is also associated with a lower incidence of obesity during childhood and adolescence, as well as with a lower blood pressure and cholesterolemia in adulthood. However, no beneficial effect of breastfeeding on cardiovascular morbidity and mortality has been shown. Maternal infection with hepatitis B and C virus is not a contraindication to breastfeeding, as opposed to HIV infection and galactosemia. A supplementation with vitamin D and K is necessary in the breastfed infant. Very few medications contraindicate breastfeeding. Premature babies can be breastfed and/or receive mother's milk and/or bank milk, provided they receive energy, protein and mineral supplements. Return to prepregnancy weight is earlier in breastfeeding mothers during the 6 months following delivery. Breastfeeding is also associated with a decreased risk of breast and ovarian cancer in the premenopausal period, and of osteoporosis in the postmenopausal period.
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ArticlesInternational multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Lancet

Lancet

J Clin Epidemiol

Lancet

Prevention of mother-to-child transmission of HIV-1 infection

AIDS

Human immunodeficiency virus type 1-infected cells in breast milk: association with immunosuppression and vitamin A deficiency

J Infect Dis

Resumption of breast-feeding in later childhood: a risk factor for mother to child human deficiency virus type 1 transmission

Pediatr Infect Dis J

Transient seroreversion in children born to HIV-1 infected mothers

Pediatr Infect Dis J

Global Programme on AIDS. Consensus statement from the WHO/UNICEF consultation on HIV transmission and breast-feeding: 30 April-1 May 1992

Wkly Epidemiol Rec

HIV and infant feeding: an interim statement

Wkly Epidemiol Rec

HIV/AIDS: the global epidemic

Wkly Epidemiol Rec

An assessment of the timing of mother-to-child transmission of HIV type-1 by means of polymerase chain reaction

J Acquir Immune Defic Syndr

HIV-1 seroconversion after 20 months of age in a cohort of breastfed children born to HIV-1-infected women in Rwanda

AIDS

Estimating the timing of mother-to-child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire

J Infect Dis

Late postnatal mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire

Lancet

Articles
International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection