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Published on 1 May 2006

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Interventions to reduce postnatal HIV transmission

teaser

Louise Kuhn
PhD
Associate Professor of Epidemiology
Department of Epidemiology
Mailman School of Public Health
Columbia University
New York, NY
USA
E:lk24@columbia.edu

Short courses of antiretroviral drugs are capable of reducing mother-to-child HIV transmission. However, these courses typically cover the perinatal period, preventing only transmission that occurs during late pregnancy or delivery.(1,2) If a mother elects to breastfeed, then the child remains at risk of postnatal HIV for the duration of breastfeeding. Although infection is not inevitable and rates of transmission are surprisingly low (approximately 10%) considering that the child consumes many litres of HIV-containing milk over many months, these infections cause substantial infant and child morbidity and mortality, reversing decades of improvement in child survival in some of the poorest countries in the world. The areas of the world, notably sub-Saharan Africa, most affected by the HIV/AIDS pandemic are also the areas where breastfeeding is common and of long duration.

Avoidance of all breastfeeding
This might seem like the simplest solution and is clearly an effective option: no exposure, no infection. However, replacing human milk, even with ­nutritionally adequate infant formula, introduces other problems. Foremost, those children lucky enough to have escaped HIV are now placed at risk of other infections such diarrhoea and pneumonia. Ordinarily, immunologically active components of breast milk would have afforded them some protection against these infections.(3) Thus, benefits of avoiding postnatal HIV infections by not breastfeeding have to be weighed against benefits of avoiding other fatal infant infections by breastfeeding.

Depending on assumptions made, the magnitudes of the risks due to avoiding breastfeeding versus practising breastfeeding are quite similar.(4) Hence, the balance is very fine and the right choice uncertain. Neither, without modification, offers an acceptable solution. Risks of formula feeding are greatest for children living in impoverished economic conditions where lack of clean water, adequate sanitation and household food security in homes exacerbate ­underlying risks. Hence, international guidelines conclude that avoidance of breastfeeding can only be recommended when breast milk substitutes are acceptable, feasible, affordable, sustainable and safe.

Infant formula is unaffordable for most ­mothers living with HIV in low-resource settings, so programmes have to provide for it to be a ­genuine option. With this comes the obligation to offer ­unbiased counselling in order to guide new mothers to informed decisions. Programmes need to ensure sustained supply and accessible distribution and provide effective education for correct and safe use. In some settings, mothers have been reluctant to avail themselves of programme-provided formula. Where breastfeeding is the norm, formula feeding may be stigmatising and result in undesired disclosure of a mother’s HIV status.

Exclusive breastfeeding
This has garnered a lot of attention as an intervention to reduce postnatal HIV transmission. At first glance, this claim may seem counterintuitive. How can more (breastfeeding) be less (transmission)? However, two large, well-conducted studies in South Africa and Zimbabwe have observed that HIV-infected mothers who fed their infants only breast milk were less likely to transmit HIV than mothers who gave other liquids and solids to complement breastfeeding.(5,6) It is hypothesised that pathogens and allogens introduced to the immature gastrointestinal system may cause inflammation, facilitating infection.

Standard lactation counselling routinely promotes exclusive breastfeeding for the first six months as the practice healthiest for mothers and babies as part of an educational package that promotes initiation of breastfeeding shortly after delivery, on-demand feeding and early identification and prevention of breast problems. Duration of exclusive ­breastfeeding increases with higher-quality lactation support programmes.(7) It is possible that reduced HIV transmission observed among exclusively ­breastfeeding mothers may be a consequence of fewer breast problems, such as mastitis. Breast problems increase the chances of transmission.(8) Exclusive ­breastfeeding may help normalise the physiological processes that regulate establishment and maintenance of milk. Mammary gland permeability is high in the early postpartum period as breastfeeding is established and increases with weaning or sudden changes in the amount of milk produced. Sodium in milk partially tracks the extent of permeability and tends to predict the quantity of virus in milk.(9) High-quality lactation may help improve the quality of breastfeeding, ­lessening periods of permeability.

Use of antiretroviral drugs
Use of these drugs over the duration of breastfeeding may prove to be the best option to reduce HIV transmission via this route. Several studies are currently underway to test longer courses of antiretroviral drugs given either to the mother or to the child. These studies need to be viewed in light of the current unprecedented global mobilisation to make HIV treatment more accessible in low-resource settings.

Any cohort of HIV-infected mothers will include some mothers whose infection is severe enough to warrant initiation of antiretroviral drugs and other mothers who do not yet need it. Mothers with advanced HIV infection (low CD4+ T-cell counts and high viral load) are also most likely to transmit to their child. Thus, lifesaving treatment for ­mothers may be lifesaving for infants too by preventing infection.

For mothers who do not yet need treatment (and this group may be large), combinations of ­antiretroviral drugs could be given for the full duration of breastfeeding and then stopped. Such an approach requires first evaluating whether regimens will, in fact, be efficacious to block transmission. There is lingering doubt because, although antiretroviral drugs rapidly reduce the amount of free virus detectable in breast milk, cell-associated virus is slower to be cleared.(10) If efficacious, risk-benefit analyses will need to consider drug side-effects for both mother and child (drug concentrations in breast milk may be high). Longer drug regimens also present major challenges for acceptability and adherence. They also require more complex healthcare infrastructures and resources than exist in many of the low-resource settings with major HIV epidemics. An effective vaccine would offer the best intervention to reduce breastfeeding transmission, but this requires a breakthrough in scientific understanding of HIV immunity. Although none of the currently available interventions is optimal for all circumstances, the challenge for service providers is to improve coverage with these imperfect interventions. Many women still do not have access to HIV testing, antiretroviral drugs or basic infant feeding information. The challenge for researchers is to improve these interventions so that breastfeeding, a practice crucial for other aspects of child development, might be made safer.

References

  1. Jackson JB, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet 2003;362:859-68.
  2. Leroy V, Karon JM, Alioum A, et al. Postnatal transmission of HIV-1 after a maternal short-course zidovudine peripartum regimen in West Africa. AIDS 2003;17:1493-501.
  3. WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. Lancet 2000;355:451-5.
  4. Kuhn L, Stein Z. Infant survival, HIV infection and feeding alternatives in less developed countries. Am J Public Health 1997;87:926-31.
  5. Iliff P, Piwoz E, Tavengwa N, et al. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 ­transmission and increases HIV-free survival. AIDS 2005;19:699-708.
  6. Coutsoudis A, Pillay K, Kuhn L, Spooner E, Tsai WY, Coovadia HM. Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001;15:379-87.
  7. Kramer MS, Chalmers B, Hodnett E, et al. Promotion of Breastfeeding Intervention Trial (PROBIT), a randomized trial in the Republic of Belarus. JAMA 2001;285:413-20.
  8. John GC, Nduati RW, Mbori-Ngacha DA, et al. Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections. J Infect Dis 2001;183:206-12.
  9. Semba RD, Kumwenda N, Hoover DR, et al. Human immunodeficiency virus load in breast milk, mastitis, and mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 1999;180:93-8.
  10. Shapiro RL, Ndung’u T, Lockman S, et al. Highly active antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1 RNA, but not DNA, in breast milk. J Infect Dis 2005;192:713-9.

Resources
World Health Organization website on HIV and Infant Feeding
W:www.who.int/child-adolescent-health/NUTRITION/HIV_infant.htm
UNICEF website on Baby Friendly Hospital Initiative
W:www.unicef.org/programme/breastfeeding/baby.htm
International Code of Marketing of Breast-milk Substitutes
W:www.who.int/nut/documents/code_english.PDF



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