Professional Documents
Culture Documents
Prevention of Mother-to-Child
Transmission of HIV Infection
Michael A. Tolle, MD, MPH
Daniel Dewey, MD
Objectives
Key Points
1. A growing proportion of HIV-infected individuals
worldwide, particularly in southern Africa, are young
women of reproductive age.
2. Infants are infected with HIV through the perinatal
route: in utero, during labor and delivery, or
postpartum through breast milk.
3. Risk factors for mother-to-child transmission of HIV
include maternal, obstetric, and postnatal factors,
including choice of infant feeding strategy.
4. In a breastfeeding population, as much as 40% of
total mother-to-child transmission of HIV may take
place during breastfeeding.
5. Mixed feeding carries a higher risk of motherto-child transmission than does either exclusive
breastfeeding or exclusive formula feeding. With
proper assessment, counseling, and support,
mothers can successfully avoid mixed feeding.
Introduction
At the end of November 2009, UNAIDS released the
latest data on the number and distribution of persons
living with human immunodeficiency virus (HIV)/AIDS
worldwide. Estimates are that of the more than 33 million
persons living worldwide with HIV/AIDS, a growing
proportion are young women of reproductive age. And
as the World Health Organization (WHO) and UNICEF
detail in the Guidance to Global Scale-up of the Prevention of
90
96
97
HIV Transmission
to the Baby at
6 Weeks of Life
HIV Transmission
to the Baby at
18 Months of Life
A. ZDV+3TC starting
at 36 weeks of
gestation, oral
intrapartum dosing,
and 7 days postpartum
dosing of mothers
and infants
5.7%
15%
B. ZDV+3TC starting
with oral intrapartum
dosing and 7 days
postpartum dosing of
mothers and infants
8.9%
18%
C. ZDV+3TC oral
intrapartum doses only
14.2%
20%
D. No intervention
15.3%
22%
103
105
Table 3. ARV-prophylaxis options recommended for HIV-infected pregnant women who do not need
treatment for their own health
Option A - Maternal ZDV
Mother
Antepartum ZDV (from as early as 14 weeks
gestation)*
sd-NVP at onset of labor*
ZDV+3TC during labor and delivery*
ZDV+3TC for 7 days postpartum*
Mother
Triple ARV from 14 weeks until one week after all exposure
to breast milk has ended:
ZDV+3TC+LPV/r
ZDV+3TC+ABC
ZDV+3TC+EFV
ZDV+3TC (or FTC) + EFV
Infant
Breastfeeding infant
Daily NVP from birth until one week after all exposure
to breast milk has ended
Infant
Breastfeeding infant
Daily NVP from birth to 6 weeks
Non-breastfeeding infant
ZDV or NVP daily for 6 weeks
Non-breastfeeding infant
ZDV or NVP daily for 6 weeks
106
Infant Feeding
Implementing a package of PMTCT measures can
generate HIV transmission rates at birth of 1%-2% in
both high-income and resource-limited settings. And yet
these impressive rates of PMTCT are not sustained in
a breastfeeding population, where breastfeeding is the
cause of up to 40% of overall transmission, and absolute
risk approaches 15% if women carry out prolonged
breastfeeding to 2 years.
Several factors increase the risk of breastfeeding trans
mission, including advanced maternal clinical stage,
low maternal CD4 count, high maternal viral load,
mastitis, and mixed feeding. The highest risk of HIV-1
transmission during breastfeeding is believed to be during
early lactation; colostrum contains higher viral loads than
milk produced later in lactation.
Yet transmission risk from breastfeeding is not restricted
to the early lactation period. The Breastfeeding and
HIV International Transmission Study (BHITS) metaanalysis has shown the risk to continue throughout the
breastfeeding period. In BHITS, the risk of postnatal HIV
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109
Mashi Trial
Conducted in Botswana, the Mashi trial was a
randomized 2 2 factorial clinical trial for HIV-infected
pregnant women and their infants. It was designed to
compare interventions for both preventing perinatal
HIV transmission and reducing postnatal HIV infection
and mortality. The postnatal portion of Mashi compared
the efficacy and safety of breastfeeding plus infant ZDV
prophylaxis for 6 months to formula feeding from birth
plus 1 month of infant ZDV. A total of 1179 infants were
studied, and points evaluated were HIV infection by
age 7 months and HIV-free survival by 18 months. The
study also evaluated safety in the form of occurrence of
infant adverse events by 7 months of age. The 7-month
Vitamin Supplementation
Maternal nutritional factors may play a role in MTCT.
Several studies have evaluated the contribution of
maternal micronutrient levels, particularly vitamin
A, to transmission risk. Vitamin A plays a key role in
maintaining the surface integrity of the mucosa, and
vitamin A deficiency is associated with immunologic
alterations, including diminished CD4+ cell number and
function. A study in Durban, South Africa, examined
whether vitamin A supplementation was associated with
reduced MTCT. Women were randomized to receive either
vitamin A supplements or a placebo. The two groups
showed no difference in the risk of HIV infection by 3
months of age. There was also no difference in overall
fetal mortality. However, there were significantly fewer
preterm births in the vitamin A group than in the group
that received the placebo. Also, among the women who
had preterm deliveries, those assigned to the vitamin
A group were less likely to transmit HIV than those
assigned to the placebo group.
Two other studies from Africa, looking at either vitamin
A or multivitamin supplementation, have confirmed
these findings. None of the three studies showed that
vitamin supplementation was effective in reducing
overall MTCT. However, all three showed that vitamin
supplementation reduced adverse pregnancy outcomes.
Multivitamin supplements are inexpensive and easy
to administer and are recommended for HIV-infected
pregnant women.
In one study carried out in a periurban South African
setting, maternal multivitamin use was significantly
correlated with increased levels of HIV RNA in the
mothers breast milk. The clinical significance of this
finding is not clear, but to date there have not been
HIV-2
Throughout this chapter, when we have used the term
HIV, we have generally referred to HIV-1. HIV-1 is far
more common and geographically distributed than HIV-2,
and most study data cited here refer to HIV-1. Yet HIV-2
infection also has consequences, and PMTCT of HIV-2
deserves special commentary.
Although transmitted in the same manner as HIV-1,
data indicate HIV-2 to be much less transmissible from
mother to child. Among breastfed infants and without
any interventions, HIV-2 has rates of MTCT in the 0%4% range. HIV-2 is endemic in West Africa, where testing
for both HIV-1 and HIV-2 is recommended for PMTCT
programs. A key feature of HIV-2 as relates specifically to
PMTCT regimens recommended by the WHO for HIV-1 in
resource-limited settings is that NNRTI drugs, including
nevirapine, are not effective against HIV-2. HIV-2 may
progress to AIDS in a similar fashion to HIV-1, although
typically progression is much slower. When a woman
living with HIV-2 infection requires HAART for her
own health, a regimen of triple NRTIs is recommended
rather than an NNRTI-based regimen (using nevirapine
or efavirenz), because HIV-2 is inherently resistant to
NNRTIs. Similarly, when a pregnant woman does not
meet HAART treatment criteria for her own health she
should be provided with ARV prophylaxis against MTCT.
The recommended regimen for ARV prophylaxis against
MTCT in HIV-2-infected women is ZDV starting at 28
weeks gestation or as soon as is feasible thereafter and
ZDV during labor. Because no nevirapine is given during
labor (because of NNRTIs inherent inactivity versus
HIV-2), the mother does not need ZDV and 3TC during
labor, nor does she need the postpartum course of ZDV
plus 3TC given to HIV-1-infected mothers who receive
SD-NVP to prevent NNRTI resistance. Infants born to
HIV-2-infected mothers should receive ZDV for 7 days
after birth. WHO recommendations for infant feeding in
the presence of maternal HIV-1 infection also apply in the
presence of HIV-2 infection. In women coinfected with
both HIV-1 and HIV-2, the recommendations detailed
113
Maternal ART
indicated
Maternal ART not indicated
Mother
Scaling Up
The recently released Guidance to Global PMTCT Scaleup promotes a country-targeted approach to reaching
universal access to services. Key in the Guidance is the
above-mentioned integration of all four components
of the WHO PMTCT strategy into a comprehensive,
longitudinal model of care.
The Guidance urges international coordinating bodies, such
as WHO, UNAIDS, and UNICEF; national governments;
and integral international nongovernmental organization
partners (of which BIPAI is one) to work together in
a common strategy to realize soon universal access to
PMTCT services worldwide, on the way to an AIDS-free
generation by 2015.
The Guidance offers 10 guiding principles in this regard:
1. Urgent scaleup to achieve national coverage and
universal access
2. Country ownership and accountability
3. Emphasizing the participation of people living with
HIV and communities
4. Strong, coordinated, and sustained partnerships
5. Aiming for both effectiveness and quality
6. Delivering a comprehensive package of services
based on the United Nations four-element strategy,
including links between services and integration
with maternal, newborn, and child health services
7. Giving priority to providing ARV therapy for treating
eligible pregnant women
8. Family-centered longitudinal care
9. The importance of male involvement
10. Improving maternal and child survival
Conclusion
The benefits of PMTCT are both obvious and substantial.
Well supported with evidence and experience, PMTCT
interventions offer an opportunity to significantly reduce
the scope of the pediatric HIV pandemic. Extending the
success seen in resource-rich settings to resource-limited
locales is both a necessary and urgent ethically sound
goal. PMTCT interventions do not exist in isolation
from one another. Scaleup of the integration of all four
References
1. UNAIDS (Joint United Nations Programme on HIV/
AIDS). December 2007 AIDS epidemic update.
2. World Health Organization. Rapid advice. Use of
antiretroviral drugs for treating pregnant women
and preventing HIV infection in infants. November
2009.
3. World Health Organization. Rapid advice. HIV
and Infant Feeding. Revised principles and
recommendations. November 2009.
4. World Health Organization, UNICEF, with the
Interagency Task Team (IATT) on prevention of
HIV Infection in Pregnant Women, Mothers, and
their Children. Guidance on global scale-up of the
prevention of mother-to-child transmission of
HIVtowards universal access for women, infants
and young children and eliminating HIV and AIDS
among children. Reported at the Global Partners
Forum, Johannesburg, South Africa, 27 November
2007.
5. World Health Organization. Antiretroviral drugs
for treating pregnant women and preventing HIV
infection in infants: toward universal access
recommendations for a public health approach.
August 2006.
6. Jourdain G, Mary J, Le Coeur S, et al. Risk factors
for in utero or intrapartum mother-to-child
transmission of human immunodeficiency virus type
1 in Thailand. J. Infect. Dis. 2007;196:1629-1636.
7. Kourtis AP, Lee FK, Abrams EJ, et al. Mother-to-child
transmission of HIV-1: timing and implications for
prevention. Lancet Infect. Dis. 2006;6:726-732.
8. Taha TE, Hoover DR, Kumwenda NI, et al. Late
postnatal transmission of HIV-1 and associated
factors. J. Infect. Dis. 2007;196:10-14.
9. Guay LA, 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: HIVNET
012 randomised trial. Lancet 1999;354:795-802.
10. United States Public Health Task Force Perinatal HIV
Guidelines Working Group. Public health service
task force recommendations for use of antiretroviral
drugs in pregnant HIV-infected women for maternal
115
11.
12.
13.
14.
15.
At onset
of labor
HAART
continues
versus ART
Until 4 weeks prior prophylaxis
to delivery
regimen;
Delivery of
newborn with
safe delivery
practices
Birth to
12 months
postpartm
Start either
HAART
or ART
prophylaxis
Birth to 4 week
postpartum
28 weeks
40 weeks
24 weeks
Patient
presents
to ANC
for
volun
tary
care and
testing
and then
draw
CD4
22 weeks
20 weeks
PMTCT timeline
Postpartum
ART for
mother
and baby
Postpartum
infant
feeding
counseling
Ongoing
longitudinal
HIV/AIDS
care and
treatment
for mother
and affected
family
members
This timeline presents the ideal for PMTCT: Early recognition of HIV-positive status, early evaluation of CD4 and decision as
to HAART versus ARV prophylaxis as well as intrapartum, postpartum, and longitudinal care for mother, infant, and family.
A key message is the realization that a delay in initiating the timeline (diagnosis of HIV positive, entry of mother into PMTCT
services) delays all subsequent events. As the text of the chapter notes, ideally mothers receive at least 4 weeks of ART
prior to delivery. This goal becomes difficult to achieveand PMTCT efficacy sufferswhen the initiation of the timeline is
delayed.
116
Lifetime
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
117
54.
55.
56.
57.
58.
59.
60.
61.
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