maternal.html
OPINION
MATERNAL AND INFANT HEALTH IS PROTECTED BY ANTIRETROVIRAL DRUG STRATEGIES THAT PRESERVE BREASTFEEDING BY HIV-POSITIVE WOMEN
Louise Kuhn,
PhD
Gertrude H Sergievsky Center, College of Physicians
and Surgeons; and Department of Epidemiology, Mailman School of Public
Health, Columbia University, New York, USA
The South African Department of Health is justified in withdrawing support for free infant formula. By so doing, it recognises
that any intervention that might detract from breast feeding poses a
serious threat to infant survival. Since evidence is now strong that
antiretroviral drugs used during lactation prevent transmission of
infection from a seropositive mother, strategies that promote breastfeeding can now be recommended for enhancing the health of mothers and infants.
The Tshwane Declaration of Support for Breastfeeding in South Africa
was recently championed by the national Department of Health as a
concrete step to improving maternal and child health in the country.
Saloojee, Gray and McIntyre (in the December 2011 edition of this
journal) state they are not opposed to this declaration, and welcome
the greater support for application of baby-friendly principles in the
health services, strengthening community-based programmes to support
breastfeeding, and stricter legislation to protect the rights of
breastfeeding mothers. They objected to only one item concerning the
withdrawal of free formula for HIV-positive women, and lamented that
there has been hardly any response from clinicians, health
professionals or civil society groups to this decision. Aside from
their objections, the overwhelming response to the Tshwane Declaration
from clinicians, health professionals and civil society groups has been
enthusiastic support. Moreover, the Tshwane Declaration itself was a
culmination of more than two years of consultation between the
Department of Health and clinicians, health professionals, civil
society groups, including activists and women living with HIV, and
Saloojee et al. themselves.
The latter authors state that the evidence base for withdrawal of formula is inadequate. In this paper,
I present the extensive evidence base supporting the new South African
government policies. The evidence is strong that provision of free
infant formula is dangerous and that antiretroviral drugs (ARVs) work. I also discuss whether withdrawal of free formula could be considered unconstitutional – a very important accusation, and one which requires thoughtful consideration.
BREASTFEEDING SAVES LIVES
Saloojee et al. assert
that to withdraw support for free formula is a luxury that South Africa
can ill afford unless there is ‘substantial evidence that the
strategy is either ineffective or results in major harm’
[emphasis added]. While these are reasonable criteria on which to make
any decision about public health, it is extraordinary that they appear
to disregard the overwhelming evidence from around the African
continent, including countries in southern Africa, that formula feeding
is associated with significantly higher mortality in young infants. It
is precisely the accumulation of substantial evidence that provision of
infant formula is either futile or results in major harm that informed
the international recommendations released by the World Health
Organization to guide national ministries of health.1
Human breast milk is exquisitely regulated, containing not only
nutrients but also immunologically active components to protect
newborns against disease and support the maturation of their own immune
system.2 Medical research
dating back to the Middle Ages identified that orphans and abandoned
infants would die unless human breast milk were provided.3
An experiment was undertaken in the 1970s by formula manufacturers,
confident in their ‘modern’ product, who began marketing it
in African countries. Provision of infant formula correlated with
infant deaths.4 Fortunately,
these deaths also sparked effective pro-breastfeeding advocacy that has
helped to shape global public health initiatives. There are extensive
biological, clinical, epidemiological and programmatic data indicating
that infant formula results in major harm to infants and their mothers.
Consequently, it is a falsehood to say that evidence showing the major
harm associated with provision of formula is ‘simply
lacking’. There is overwhelming evidence of the harmful effects
of formula feeding in the general population in southern Africa and
elsewhere for decades. Until recently, there was indeed a lack of
evidence of any comparable effect among HIV-infected mothers and their
exposed but uninfected infants. Yet there is now substantial evidence
in better- and less-resourced settings, including the better-resourced
settings of South Africa and Botswana, that formula feeding results in
elevated death rates among children who would otherwise be
HIV-uninfected and alive. The serious threat to infant survival is the
most important justification for the withdrawal of Department of Health
support for infant formula.
IS HIV IN SOUTH AFRICA THE EXCEPTION?
Saloojee et al. do not
appear to be aware of this expanse of biological, clinical,
epidemiological and programatic research. It seems that their position
can only be held if they subscribe to two types of
‘exceptionalism’: (i) HIV exceptionalism and (ii) South African exceptionalism.
Postnatal transmission of HIV through breastfeeding is indeed a
special case that requires cautious and courageous consideration of
appropriate infant feeding policy. HIV transmission can occur
throughout the period of breastfeeding, therefore complete abstention
from breastfeeding will obviously not permit any transmission to occur
via this route. Abstention from breastfeeding will not, however,
prevent intrauterine or intrapartum transmission. In the absence of
interventions, most (~70%) infants born to and breastfed by
HIV-positive mothers will remain uninfected. When HIV-positive women
avoid breastfeeding with the goal of preventing the proportion of
vertical transmission attributable to breastfeeding, they place their
infants at risk of malnutrition, pneumonia and diarrhoeal morbidity and
mortality as well as increasing the child’s risk of developmental
and cognitive delays. This is the nub of the dilemma, and provision of
free formula is not a solution; instead, it’s part of the dilemma
that the HIV epidemic has made us face.
In the era prior to the demonstration that ARVs used during
lactation can provide a constructive solution to the infant-feeding
dilemma, two wish-fulfillment strategies were used instead: Either deny
that HIV is transmitted through breastfeeding or deny that there are
substantial risks of death and other serious outcomes from formula
feeding. Study after study clearly showed that HIV is transmitted to
infants through breastfeeding. Denial of the dangers of formula became
the more popular position. In 2000, the WHO recommended that
HIV-infected women provide formula feeds to their infants as a means of
preventing HIV infection. This guidance was based on the premise and
intention that public health programmes could be set up that would
eliminate the risks associated with handing out formula feeds. This
strategy was very powerful because it was able to mobilise resources to
buy formula for programmes and for research. But the strategy set aside
the large body of breastfeeding research that had been conducted among
non-HIV-infected women that had described and quantified the excess
risk of death associated with formula feeds; it called for new research
and evidence to record the experiences and measure the effects of using
formula feeds by HIV-infected mothers.
For better or worse, several groups, including my own, bought into
this notion and conducted studies to test whether complete avoidance of
breastfeeding, or shortening the duration of breastfeeding, would have
adverse consequences for infants born to HIV-positive mothers. Sadly,
they did. These well-conducted, rigorous research studies with results
that have been reviewed by peer scientists prior to publication in
leading medical journals were conducted in a wide range of settings in
Africa, including better-resourced settings such as Botswana and South
Africa. For example, in a clinical trial in urban Botswana where women
were randomised either to formula from birth or breastfeeding for 6
months, a doubled risk of death was observed among uninfected infants
born to HIV-infected mothers.5
In this study, participants were carefully screened to ensure all had
access to clean water and adequate sanitation, formula was provided
free, counselling and support around formula feeding was extensive, and
there was a well-functioning health service safety net. In another
example in a well-resourced area in rural Uganda, with a sophisticated
health service, women were counselled about infant feeding options
following AFASS (affordable, feasible, acceptable, sustainable and safe
– the acronym summarising the criteria that were proposed at that
time as the requirement for formula feeding to be the better choice)
and a 6-times greater risk of infant mortality was observed among women
who selected formula feeding because they felt it was
‘AFASS’ for themselves.6 There are several other studies, including numerous studies from South Africa.7
The consistency of the findings across diverse settings, across
different study designs and with established biological processes makes
it highly unlikely that the dangers of formula can be explained away as
part of the vagaries of clinical research methodology. The findings of
these studies, in conjunction with research findings demonstrating the
efficacy of ARVs to significantly reduce the risk of HIV infection
through breastfeeding, iteratively led the WHO to revise its
recommendations from a position of recommending formula feeds as the
default feeding practice for HIV-infected mothers, to recommending
breastfeeding with ARVs.
Saloojee et al. dismiss
this large body of research with the claim that it comes from settings
with much higher rates of infant morbidity and mortality than those
observed in South Africa (or those parts of South Africa with more
resources). This is not true i.r.o. Botswana and other countries, such
as Zambia and Malawi, that are more economically disadvantaged, and
manifests a confusion between an absolute and a relative risk. An
absolute risk quantifies the likelihood that an event will occur in a
group; e.g. the risk of dying is 40 per 1 000. A relative risk compares
two groups: group A has an absolute risk of 40 per 1 000 and group B
has an absolute risk of 80 per 1 000, therefore the relative risk of
group B v. group A is double. Even in countries with very low absolute
rates of infant mortality, such as the USA, UK and the Netherlands,
formula increases mortality; i.e. the relative risk is elevated.15
But in countries with higher absolute infant mortality rates, the same
relative risks translate into a larger absolute number of infant
deaths. Moreover, synergy occurs: in populations with high absolute
mortality rates, relative risks of death owing to formula are also
higher; for example, water contamination, lack of access to adequate
sanitation and poor health service infrastructure exacerbate the
dangers of formula. But economic disadvantage does not create the
biological disadvantage of formula. There is no threshold below which
formula no longer causes harm. Breastfeeding saves lives in all
countries – South Africa is no exception.
Saloojee et al. misquote three studies18
as evidence that replacement feeding can be safely accomplished. These
studies do report equivalent or better outcomes with replacement
feeding; however, the outcome reported is HIV-free survival, and at a
time when ARVs were not available to prevent HIV infection through
breastfeeding. HIV-free survival is a composite endpoint defined by the
absence of either infant HIV infection or infant death. As a public
health indicator, it is useful as it reminds us that there is little
point in saving infants from HIV if they are only going to die of other
causes. However, consideration of only HIV-free survival does not
provide proof of safety of formula feeds. Equivalent
HIV-free survival means that the number of HIV infections averted has
been cancelled by the number of additional uninfected deaths caused.
These stark statistics do not resolve the question of whether
breastfeeding alone or formula feeding is the better feeding practice
for HIV-exposed infants. New data from research studies undertaken in
over 6 countries, including South Africa, completely transform the
context in which the dilemma of infant feeding by HIV-infected mothers
should be considered. ARV intervention can be used during breastfeeding
to reduce the risk of transmission.21
None of the studies referred to above used ARVs during breastfeeding;
the Kenyan study was done before even short-course perinatal
interventions became available. These studies are uninformative for the
current era when ARVs are available to prevent transmission through
breastfeeding. Saloojee and colleagues remain locked into an evidence
base and paradigm that does not recognise the potency of ARVs and the
opportunity they present to improve the health and survival of
HIV-exposed infants.
SOUTH AFRICA HAS PERSISTING INEQUITIES IN HEALTH AND WEALTH
As an argument in support of free formula, Saloojee et al.
remind us that South Africa is not a single homogenous country. This is
absolutely true. South Africa is a country is with gross disparities in
wealth, health and living conditions. This is not an argument for the
government to support formula for the better-off. To the contrary, new
government policies can serve to reduce inequities and provide highly
effective interventions to everyone and not just a number of favoured
groups; the new national policies proactively consider the needs of the
poor first – as public health policies should.
In Saloojee et al.’s
view, the government should provide free formula for women in the
wealthier provinces, such as Gauteng and Western Cape, where women are
sufficiently well-off to meet AFASS criteria but not so much as to
purchase formula themselves. Yet this contradicts the first
‘A’ of AFASS, which is ‘affordable’ – a
point which they seem to ignore. But it’s not actually the A
which is most relevant – it’s the S for safety. Back to the
first point: formula feeding is dangerous.
STUDY THE NUMBERS – THEY MATTER
It is therefore, reasonable to ask why HIV-positive women in
the United States are required to formula feed. It is imperative to pay
close attention to the actual absolute and relative risks in the South
African context. Saloojee et al. in their protest to the Mail & Guardian
claim that, since infant mortality may be as low as 25 per 1 000 in
some better-off parts of South Africa, this figure is below the
‘accepted’ threshold where formula feeding can be
considered ‘safe’. The basis for this claim is mathematical
modelling, conducted by several different groups (including myself)29
in the 1990s, calculating the competing risks of HIV transmission
associated with breastfeeding v. the increased risk of uninfected child
deaths owing to abstention from breastfeeding. A ‘safe’
threshold is the point at which the number of HIV infections averted by
formula is exactly equivalent to the number of deaths caused by formula
feeding – hardly a basis for a resounding endorsement of formula.
Nevertheless, the primary limitation of the models used by Saloojee et al.
is that they ignore the new opportunities provided by ARV strategies.
ARVs, when used throughout lactation, significantly reduce the risk of
HIV transmission via lactation.30
If one applies the new rates of HIV transmission observed when ARVs are
given, the infant mortality rate has to fall to below 10 per 1 000
before the increased number of deaths caused by formula feeding is
counterbalanced by the number of HIV infections averted. Only when the
infant mortality rate is <8 per 1 000 live births, is formula able
to save one child per 1 000. If transmission rates are lower than
assumed in the model, and are as low as observed in clinical trials,
such as the trial in Botswana,22 or risks associated with formula feeding are higher than observed in clinical trial settings,5
as is likely to occur in practice, infant mortality rates need to be
even lower before formula can be considered a desirable option (Fig.
1). The infant mortality rate is nowhere near this level in any of the
populations affected by HIV in South Africa, even in the wealthier
provinces. New government policies take into account the newest
up-to-date data, in contrast to the complaints made by Salojee et al. that rely on out-of-date data and arguments that exclude the availability of ARVs.
ANTIRETROVIRAL DRUGS PROVIDE A SOLUTION TO THE INFANT FEEDING DILEMMA
Many commentators are blithely optimistic about the safety of
formula, yet this optimism does not extend to ARV strategies. Regarding
the benefits of ARV strategies to prevent mother-to-child HIV
transmission, they state these strategies are unproven, based on
inference, and with many ‘unanswered questions’. This is
surprising, since these authors have been at the forefront of testing
ARV drug strategies and have published data showing the efficacy and
safety of drug interventions and have been highly active in supporting
their successful roll-out in Gauteng and elsewhere in South Africa.31
,
32
South African researchers have a stellar record in implementing
ARV-based programmes including demonstrating the capacity of the
routine health services to provide effective ARV strategies for
pregnant HIV-positive women.33
This is not to say that ARV programmes are easy to implement and that
they may fall short. But pessimism, and claiming that failure to
implement perfect programmes will have ‘drastic
consequences’, damages mobilisation of resources and the will to
implement these programmes. ARV drug strategies are highly effective in
reducing mother-to-child HIV transmission through all routes, including
breastfeeding, and save women’s lives. Programmes to implement
these strategies should be supported, not disparaged.
My major concern about this pessimism is that it implies that
formula is a better option than ARV drugs. This is deeply disturbing
because formula does nothing to prevent mother-to-child transmission
that can occur during pregnancy and delivery. Formula does nothing to
improve maternal health. Even if formula is provided, ARV treatment and
prophylactic regimens remain vital. Based on current criteria, a large
proportion of pregnant HIV-positive women meet criteria for ARV
treatment. They need this treatment as a matter of urgency for their
own survival and well-being, and this treatment needs to be lifelong.
To my mind, it is problematic to argue against ARV therapy because
formula is more cost-effective in preventing HIV transmission in a
select group of mothers and children. Women who meet criteria for
treatment are responsible for a large proportion of the infant
infections (>80% of postnatal infections).36
Therefore, purely implementing standard adult guidelines for provision
of ARV therapy for pregnant women who require it based on their own
health status would address the majority of postnatal HIV infections
and would also reduce maternal deaths. Choices of infant nevirapine
prophylaxis (option A), or therapeutic regimens that are stopped after
the cessation of breastfeeding (option B), are available to address the
remaining small proportion, but apply only to those asymptomatic women
with high CD4 counts. The focus of public health interventions needs to
be on reaching the women who need treatment for their own health and
who are also most likely to transmit.
HIV IS NOT THE ONLY DISEASE FROM WHICH CHILDREN NEED TO BE PROTECTED
Saloojee et al. argue
that ‘[a]n HIV-free generation can never be achieved while
breastfeeding continues.’ This is true. But this statement could
be more properly rephrased ‘An HIV-free generation can never be
achieved while pregnancy
continues.’
Current ARV drug regimens do not result in zero transmission even in
formula-fed populations. When ARV drug regimens were started early in
pregnancy and continued through breastfeeding in a study in Botswana,
the overall transmission rate, including transmissions that occurred
during breastfeeding, was 1.1%. More than 75% of the HIV infections
were detected at birth and had occurred before delivery. Transmission
during 6 months of breastfeeding when ARV drugs were given was 0.28%.22
Eliminating breastfeeding will not eliminate HIV transmission.
Eliminating breastfeeding will, however, increase infant mortality.
BREASTFEEDING RIGHTS AND WRONGS
It was not clear from the arguments presented by Saloojee et al.
what the basis was for the charge that withdrawal of free formula was
unconstitutional. It may be the denial of the ‘opportunity to
have an HIV-uninfected child’ that will result if women are
denied access to formula despite meeting AFASS criteria. This rhetoric
is seductive but not based on fact. Formula will not guarantee that an
HIV-positive woman has an uninfected child. Without ARV drugs,
transmission will occur during pregnancy or delivery in about a quarter
of women. With adequate ARV drugs given during pregnancy and then
stopped, transmission rates would be around 2%, assuming complete
abstinence from breastfeeding. A woman may have a ‘right’
(in the broadest sense of the word) to purchase harmful commodities if
she so chooses – just as she has a ‘right’ to smoke
during pregnancy if she so chooses. However, to claim that a woman has
a constitutional right to be given harmful products by the health
services simply because they prevent HIV transmission, is wrong.
Moreover, Saloojee et al.
fail to mention children’s rights, also protected in the South
African constitution and detailed in the Convention of the Rights of
Children. This is more than just avoidance of HIV infection.
Health policies should not be decided upon by popularity contest.
National health authorities should solicit opinions on policies so that
they are sensitive to communities’ needs, but the policies
themselves need to be based on biological and public health principles
and evidence. Involvement of the HIV-infected and -affected community
is central. Children, who can be both infected and affected by HIV,
need special lobby groups to attend to their interests. The majority of
HIV-positive women care about HIV transmission to their infants and
their overall health, well-being and survival. The answer of the health
service to an HIV-positive woman’s question about how best to
feed her infant should not be a blunt ‘your choice’.
A WAY FORWARD
It is time to put aside polarising debates and conflicts, and come
together to address the fundamental public health challenges facing
South Africa. Programmes to support breastfeeding need to be
strengthened. This includes addressing the education of healthcare
workers so that correct information is conveyed to parents, as well as
activism to challenge labour and other policies that deny the rights of
breastfeeding women. HIV can be treated with ARVs, and those receiving
ARVs have a very low risk of transmitting HIV to their child or sexual
partners. We should synergise to ensure that all people living with HIV
have access to effective care and treatment. Strengthening these ARV
programmes can greatly improve maternal and child health in South
Africa.
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Fig.
1. Breastfeeding with ARVs results in better HIV-free survival when
infant mortality rates exceed 10 per 1 000. The graph shows excess
adverse outcomes (uninfected infant deaths or HIV infections) per 1 000
as a result of formula-feeding, compared with breastfeeding among
HIV-infected women in populations of varying infant mortality rates.
The models allow a transmission rate (TR) of 2% assuming ARVs are given
and a best-case scenario of 1.3%, consistent with the Botswana clinical
trial22 of which 0.3% were
due to breastfeeding acquired infections. The model assumes a relative
risk (RR) of 2 which is consistent with best-case scenario of clinical
trial-supported formula feeding in a better-off environment 5
and considers RR=3 more likely to represent the programmatic setting.
All values >0 indicate that breastfeeding results in better net
outcomes; values <0 indicate that formula-feeding results in better
net outcomes.