Current knowledge and future research on infant feeding in the context of HIV: basic, clinical, behavioral, and programmatic perspectives.
ABSTRACT In 2008, between 129,000 and 194,000 of the 430,000 pediatric HIV infections worldwide were attributable to breastfeeding. Yet in many settings, the health, economic, and social consequences of not breastfeeding would have dire consequences for many more children. In the first part of this review we provide an overview of current knowledge about infant feeding in the context of HIV. Namely, we describe the benefits and risks of breastmilk, the evolution of recommended infant feeding modalities in high-income and low-income countries in the last two decades, and contextualize the recently revised guidelines for infant feeding in the context of HIV current knowledge. In the second section, we suggest areas for future research on the postnatal prevention of mother-to-child transmission of HIV (PMTCT) in developing and industrialized countries. We suggest two shifts in perspective. The first is to evaluate PMTCT interventions more holistically, to include the psychosocial and economic consequences as well as the biomedical ones. The second shift in perspective should be one that contextualizes postnatal PMTCT efforts in the cascade of maternal health services. We conclude by discussing basic, clinical, behavioral, and programmatic research questions pertaining to a number of PMTCT efforts, including extended postnatal ARV prophylaxis, exclusive breastfeeding promotion, counseling, breast milk pasteurization, breast milk banking, novel techniques for making breast milk safer, and optimal breastfeeding practices. We believe the research efforts outlined here will maximize the number of healthy, thriving, HIV-free children around the world.
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ABSTRACT: Background The prevention of mother-to-child transmission (PMTCT) program in South Africa is now successful in ensuring HIV-free survival for most HIV-exposed children, but gaps in PMTCT coverage remain. The study objective was to identify missed opportunities for prevention of mother-to-child transmission of HIV using the four PMTCT stages outlined in National Guidelines. Methods This descriptive study enrolled HIV-exposed children who were below the age of 7 years and therefore born during the South African PMTCT era. The study site was in Gauteng, South Africa and enrolment was from June 2009 to May 2010. The clinical history was obtained through a structured caregiver interview and review of medical records and included socio-demographic data, medical history, HIV interventions, infant feeding information and HIV results. The study group was divided into the "single dose nevirapine" ("sdNVP") and "dual-therapy" (nevirapine & zidovudine) groups due to PMTCT program change in February 2008, with subsequent comparison between the groups regarding PMTCT steps during the preconception stage, antenatal care, labor and delivery and postpartum care. Results Two-hundred-and-one HIV-exposed children were enrolled: 137 (68%) children were HIV infected and 64 (32%) were HIV uninfected. All children were born between 2002 and 2009, with 78 (39%) in the "sdNVP" and 123 (61%) in the "dual-therapy" groups. The results demonstrate significant improvements in antenatal HIV testing and PMTCT enrolment, known maternal HIV diagnosis at delivery, mother-infant antiretroviral interventions and infant HIV-diagnosis and cotrimoxazole prophylaxis. Missed opportunities without improvement include pre-conceptual HIV-services and family planning, tuberculosis screening, HIV disclosure, psychosocial support and postnatal care. Not receiving consistent infant feeding messaging was the only PMTCT component that worsened over time. Conclusions Multiple missed opportunities for optimal PMTCT were identified, which collectively increase children's risk of HIV acquisition. Although HIV-testing and antiretroviral interventions improved, all PMTCT components need to be optimized to reach the goal of total pediatric HIV elimination.BMC Public Health 12/2014; · 2.32 Impact Factor
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ABSTRACT: Abstract Introduction: Poor infant feeding practices are common in Africa, resulting in physical and intellectual developmental impairments. Good feeding practices are crucial, especially in the first year of growth. HIV/AIDS has worsened the clinical and nutritional status of both mothers and their children, exacerbating high rates of malnutrition. The aim of this study was to assess by participative approach, the nutritional status of infants from mothers tested positive to HIV in the health district of Dschang. Methods: This is a cross sectional study with a period of recruitment of 2 years (2010-2012). Data Collection was done by the aim of a personal slip followed by training to strengthen the nutritional and hygienic capacity of targeted parents. Height and weight of infants were measured and body mass index (BMI) calculated. Results: Significant difference (p ≤ 0.05) was noticed in height-for-age z-score (HAZ) of girls aged between 1 to 2 years compared to 1-year old girls as well as to boys of all ages, defining them as stunted. Furthermore, the weight-for-age z-score (WAZ) results indicate that both girls and boys of all age are in moderate state of malnutrition. The results of BMI thinness classified according to gender and age groups, indicates that most infants (68/130, 52.3%) showed grade 2 thinness predominantly in 2-years old both boys and girls. However, no participants fall within the normal category for age and sex, as well as overweight and obesity categories. Conclusion: Undernutrition exists among infants from mothers tested positive to HIV residing in Dschang, as most of the infants are underweight, and malnourished.The Pan African Medical Journal - ISSN 1937-8688. 05/2014; 18(91).
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ABSTRACT: Guidelines for prevention of mother-to-child transmission of HIV have developed rapidly, yet little is known about how outcomes of HIV-exposed infants have changed over time. We describe HIV-exposed infant outcomes in Kinshasa, Democratic Republic of Congo, between 2007 and 2013.AIDS (London, England) 07/2014; 28 Suppl 3:S301-S311. · 6.56 Impact Factor
Current Knowledge and Future Research on Infant
Feeding in the Context of HIV: Basic, Clinical,
Behavioral, and Programmatic Perspectives1,2
Sera L. Young,3,4* Mduduzi N. N. Mbuya,5Caroline J. Chantry,6Eveline P. Geubbels,7Kiersten Israel-Ballard,8
Deborah Cohan,3Stephen A. Vosti,9and Michael C. Latham4
3Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94110;4Division of Nutritional
Sciences, Cornell University, Ithaca, NY 14853;5Zvitambo Project, Harare, Zimbabwe;6Department of Pediatrics, University of California Davis
Medical Center, Sacramento, CA, 95817;7Ifakara Health Institute, Dar es Salaam, Tanzania;8PATH, Seattle, WA, 98109; and9Department of
Agricultural and Resource Economics, University of California, Davis, CA 95616
In 2008, between 129,000 and 194,000 of the 430,000 pediatric HIV infections worldwide were attributable to breastfeeding. Yet in many settings,
the health, economic, and social consequences of not breastfeeding would have dire consequences for many more children. In the first part of
this review we provide an overview of current knowledge about infant feeding in the context of HIV. Namely, we describe the benefits and risks
of breastmilk, the evolution of recommended infant feeding modalities in high-income and low-income countries in the last two decades, and
contextualize the recently revised guidelines for infant feeding in the context of HIV current knowledge. In the second section, we suggest areas
for future research on the postnatal prevention of mother-to-child transmission of HIV (PMTCT) in developing and industrialized countries. We
suggest two shifts in perspective. The first is to evaluate PMTCT interventions more holistically, to include the psychosocial and economic
consequences as well as the biomedical ones. The second shift in perspective should be one that contextualizes postnatal PMTCT efforts in the
cascade of maternal health services. We conclude by discussing basic, clinical, behavioral, and programmatic research questions pertaining to a
number of PMTCT efforts, including extended postnatal ARV prophylaxis, exclusive breastfeeding promotion, counseling, breast milk
pasteurization, breast milk banking, novel techniques for making breast milk safer, and optimal breastfeeding practices. We believe the research
efforts outlined here will maximize the number of healthy, thriving, HIV-free children around the world. Adv. Nutr. 2: 225–243, 2011.
Breastfeeding is a pillar of child survival; it reduces mor-
bidity and mortality in children worldwide (1). However,
since the early 1980s when it was discovered that HIV could
be transmitted to infants through human milk, the healthful-
ness of breastfeeding has been questioned, because of the risk
of mother-to-child transmission of HIV (MTCT).10[A note
on terminology: The International AIDS Society has been ad-
vised, in particular by networks of women living with HIV,
that the term “prevention of vertical transmission” should be
used instead of “preventing mother-to-child transmission
(PMTCT)” (3). The concern is that “PMTCT” can sound
stigmatizing in that it assigns blame to the mother. When
the term PMTCT is used by UN agencies, it is understood
to describe 4 pillars of preventing vertical transmission
(3). In this paper, we use the terms PMTCT and MTCT in
this broad sense of prevention and without any implication
of culpability]. Indeed, scientists, policymakers, and pro-
gram managers have spent the last several decades struggling
to characterize the proportion of risk of MTCTattributable
to breast milk and to develop appropriate and feasible guide-
lines on infant feeding in settings where HIVis present (4,5).
For this reason, it has been said that the HIV pandemic has
threatened to “knock breastfeeding off its pedestal as a pillar
of child survival” (6).
The aim of this paper is to presentan overview of current
knowledge of infant feeding in the context of HIV and to
10Abbreviations used: AFASS, acceptable, feasible, affordable, sustainable, and safe; ARV,
antiretroviral; EBF, exclusive breastfeeding, exclusively breastfed; HAART, highly activated
antiretroviral therapy; MTCT, mother-to-child transmission of HIV; PMTCT, prevention of
mother-to-child transmission of HIV; sdNVP, single-dose nevirapine.
*To whom correspondence should be addressed. E-mail: email@example.com.
1Supported by NIH/National Institutes of Allergies and Infectious Diseases 5T32AI065388-04 to
S.L.Y. M.N.N.M. was supported by UK Department for International Development/Zimbabwe
grant no. AG 201 854-101.
2Author disclosures: S. L. Young, M. N. N. Mbuya, C. J. Chantry, E. P. Geubbels, K.
Israel-Ballard, D. Cohan, S. A. Vosti, and M. C. Latham, no conflicts of interest.
ã2011 American Society for Nutrition. Adv. Nutr. 2: 225–243, 2011; doi:10.3945/an.110.000224.
by guest on May 18, 2011
highlight areas in which research is most urgently needed.
Such a review is timely given the WHO’s recent revision of
the guidelines on infant feeding and HIV (7). We first pre-
sent a discussion of the health benefits and risks of breast
milk, followed bya short,chronological reviewof the history
of infant feeding modalities that have been recommended in
the context of HIV in the past several decades. We then con-
textualize the 2010 recommendations bydiscussing biomed-
ical, social, and economic issues surrounding their current
implementation. In the second part of this paper, we suggest
areas for future research in infant feeding and related pre-
vention of MTCT (PMTCT), recommendations that we
think could have the biggest effect on improving the health
of HIV-exposed infants. Basic, clinical, behavioral, and pro-
grammatic research questions are outlined for each area. It
should not be forgotten, however, that infant feeding behav-
iors are only one aspect of vertical transmission and that the
prevention of vertical transmission, in turn, is only 1 of the
4 components of the WHO’s comprehensive strategic ap-
proach to the prevention of HIV infection in infants and
young children (8). Eradication of vertical transmission of
HIV must include the prevention of infection among women
of reproductive age, prevention of unintended pregnancies
among HIV-infected women, and provision of adequate
treatment, care, and support to HIV-infected women and
their families. In this review, however, we limit our discussion
to PMTCT issues, with a particular emphasis on postnatal
Current knowledge and recommendations
Risks and benefits of breast milk
Beneficial components of human milk. The short-term and
for both the mother and her infant. In the short-term, breast-
feeding decreases postpartum blood loss and promotes bond-
ing betweenmotherandchild(6,9).Longer term,for women,
it is associated with reduction in risks of breast and ovarian
cancers, retained gestational weight gain, type 2 diabetes,
myocardial infarction, and metabolic syndrome as well as
delayed resumption of menses (lactational amenorrhea),
which is important for birth spacing (9–11). For infants,
breastfeeding is unequalled in its role in reducing morbidities
and improving child growth, development, and survival in
developing (12–14) and industrialized (10,15) countries.In ad-
dition to the well-established role of breast milk in preventing
infectious diseases in infants, it reduces the risks of childhood
obesity, type 1 and type 2 diabetes, leukemia, and sudden in-
fant death syndrome (15).
The protective effects of human milk are due in part to its
optimal nutritional composition (16). Breast milk typically
provides most of the protein and energy needs of infants
even in the latter part of the first year of life as well as a ma-
jority of several critical micronutrients such as vitamins A, C,
and B-12 and folate and copper (17). These nutrients are not
easily replaced by complementary feeding in the best of cir-
cumstances and less so in low-income populations (18).
Human milk is also beneficial because of its important
and myriad immunological and antiinfective factors (19).
They include, among many others, proteins with antimicro-
bial properties such as secretory IgA, lysozyme, and lactofer-
rin; lactoferrin provides immune-modulating properties in
addition to its better-known antiinfective properties. Oligo-
saccharides in breast milk inhibit bacterial adhesion, further
protecting against pathogens, and white blood cells provide
passive immune protection. Nucleotides and cytokines also
assistwith T-cellmaturationand immunesystem modulation,
evidenced by, e.g., the more robust immune response that
breast-fed infants exhibit after vaccination (20). Breast milk
also promotes healthful gastrointestinal microbiota (21,22).
Health risks of breast milk: HIV transmission. Because
lactation is a metabolically expensive process, there was initial
concern that breastfeeding could be deleterious to HIV-
infected mothers’ health (23). Several studies have since been
unable to demonstrate any adverse consequences for mater-
nal health (24–27). Furthermore, a meta-analysis conducted
by the Breastfeeding and HIV International Transmission
Study Group indicated that mothers’ mortality during the
ing to children’s feeding modality (ever vs. never breast-fed)
(28). The apparent mortality and other health risks in HIV-
infected breastfeeding women were explained by confound-
ing. That is, HIV-infected women with lower CD4 counts
wereless likely to initiate breastfeeding and healthier women
were able to breastfeed longer. However, because greater fat
loss (29) and micronutrient deficiencies (30) have been ob-
served during lactation among HIV-infected compared to un-
infected women, some concerns remain about potentially
unmet nutritional requirements of lactating HIV-infected
women. However, in general, the major risk of breastfeeding
is vertical transmission of HIV and not adverse health effects
for the mother.
In 2008, ~430,000 (240,000–610,000) children became
infected with HIV; 90% of these were due to vertical trans-
nancy, labor, and delivery, as well as postpartum, through
breastfeeding. The risk of transmission depends on many fac-
tors, including the timing of maternal infection, maternal viral
load, immune function, nutritional status of both the woman
and baby, antiretroviral (ARV) use, breast health (nipple pa-
thology, mastitis), type of breastfeeding (exclusive, mixed, or
replacement feeding) (Table 1), duration of any breastfeeding,
and presence of oral lesions in the infant (32–37).
In the absence of interventions to prevent transmission,
5–10% of infants born to HIV-positive mothers become
infected with HIV during pregnancy and 10–20% become
infected around the time of delivery (31,33). Estimates of
the risks of HIV infection via breast milk have varied due
to the multifactorial nature of risk of transmission, includ-
ing the difficulty of quantifying the instantaneous hazard
rate of infection (38). In 1999, De Cock et al. (33) calculated
that between 5 and 20% of infants would become infected if
breastfed beyond 18 mo. A meta-analysisby the Breastfeeding
226Young et al.
by guest on May 18, 2011
and HIV International Transmission Study Group found
that 42% of infections were attributable to breast milk
(32). Kourtis et al. (39) calculated that without any interven-
tion, ~6% of HIV-negative but exposed infants would be-
come infected via breastfeeding if they were exclusively
breastfed (EBF) for 6 mo and rapidly weaned, 11% would
become infected if they weremixed fed for6 mothenrapidly
weaned, and 15% of infants would become infected if they
were breastfed for 2 y.
With currently implemented prenatal and perinatalinter-
ventions, one-third to one-half of all MTCT is estimated to
occur in the postpartum period, i.e. through breastfeeding
(40). Although the proportion of postnatal transmission at-
tributable to breastfeeding is not known exactly, it is likely
steadily increasing as prenatal and peripartum ARV prophy-
laxis continues to have increased availability and use in sub-
Saharan Africa (39,41).
Health risks of not breastfeeding: increased morbidity
and mortality. In general pediatric populations, i.e. those
not specifically HIV exposed, replacement of breastfeeding
with formulamilks, animalmilks,and otherfoods isattended
by increased mortality, morbidity, poor growth, and develop-
ment in both developing (1,14) and industrialized (42,43)
countries. Pooled analyses of data from developing countries
demonstrated that breastfeeding was strongly protective
against mortality from infectious disease (13). The OR of sur-
vival among breast-fed infants 0–1 mo old was 5.8 (CI 3.4–
9.8), 4.1 for 2–3 mo old (CI 2.7–6.4), 2.5 for 4–5 mo (CI
1.6–3.9), and 1.8 for 6–8 mo (CI 1.2–2.8). For second-year
tive effects of breastfeeding are most striking in developing
countries, but they are clear in industrialized settings as well.
Pooled analyses of mortality by breastfeeding modality in in-
dustrialized countries is not available, but postneonatal infant
mortality rates in the United States were 21% lower among
ever breast-fed infants (44).
Specifically among HIV-exposed children, multiple stud-
ies in low-income settings have documented increased mor-
bidity and mortality associated with earlier cessation of
a mean duration of any breastfeeding of 4.0 mo compared to
9.3 mo in a later trial was associated with higher rates of se-
vere gastroenteritis (8.0 vs. 3.1 episodes/1000 child-months;
P < 0.001) (45). Similarly, cessation of breastfeeding by 6 mo
of age compared to prolonged breastfeeding in Malawi re-
sulted in greater rates of hospitalization for gastroenteritis
(2.9 vs. 0.1% at 7–9 mo and 1.6 vs. 0.2% at 10–12 mo;
P < 0.001) and higher gastroenteritis related mortality
(19 vs. 7/1000 infants at 9 mo and 24 vs. 12/1000 infants
at 12 mo; P = 0.0002) (46). In Zambia, a significantly greater
decrease in weight-for-age Z-scores between 4 and 16 mo
was reported among HIV-exposed, uninfected infants who
stopped breastfeeding at 4 mo compared to those who con-
tinued (47). In Zimbabwe, infants whose mothers opted to
cease breastfeeding at 9 mo after receipt of an HIV-PCR-
negative result were fed grossly inadequate diets compared
to those who continued to receive breast milk (48). During
an outbreak of diarrhea in Botswana in 2006, HIV-exposed
infants who were receiving formula provided free of charge
were at much greater risk of death than their breast-fed peers
(49,50). In summary, not breastfeeding increases morbidity
and mortality in HIV-exposed and unexposed children in de-
veloping and industrialized countries.
HIV-free survival. Given that on one hand, breast milk can
be a vector for HIV, but on the other hand, infants, particu-
larly those in low-income settings, are at increased risk of
malnutrition, diarrhea, acute respiratory infection, and death
if they are not breastfed, any treatment of the issue of infant
feeding and HIV must necessarily address the concept of bal-
anced risks. The concept of HIV-free survival is one that cap-
tures the risks of both outcomes and is therefore a more
balanced metric of success (safety) of an infant feeding mo-
dality. In using this concept, it is important to emphasize,
however, that it reflects the desired outcome of a baby staying
HIV-negative and alive. It does not imply that an HIV infec-
tion is equivalent to a death (38). One disadvantage to using
this measurement is that it can “stack the deck in favor of in-
terventions that prevent HIV transmission and neglect the
range of other nonfatal, but potentially serious, adverse out-
ically report HIV-free survival to 18 mo (7; Annex 2), with
some reporting up to 24 mo of age (51).
Because of the limitations of the concept of HIV-free sur-
vival, the health of a population might better be measured in
terms of HIV-free “thrival” (survival + thriving), which is a
more comprehensive metric, because it captures not just if
the child is alive,but howwell she or he is doing. In this con-
text, thriving could be operationalized as normal growth, i.e.
no stunting or wasting. Thus, thrival measures some of the
outcomes that may be associated with recurrent illnesses or
malnutrition arising from early cessation of breastfeeding
and is therefore not biased toward interventions that simply
Table 1. Explanation of use of infant feeding terms1
Infant feeding terms
EBF is defined as the receipt of only breast milk (either directly from the
breast or expressed); only oral rehydration solution, drops, and syrups
(vitamins, minerals, or medicines) are permitted (207).
Mixed feeding is the receipt of both breast milk and other solids or
liquids, including water and nonhuman milks, before 6 mo of
age (208). Mixed feeding in the setting of HIV is often used
interchangeably with non-EBF and even complementary feeding.
Complementary feeding is used prescriptively to mean the appropriate
addition of other solids, semisolids, and liquids to a breastfeeding
infant’s diet at w6 mo of age and thereafter (206).
Replacement feeding indicates that the infant receives no breast milk
but is fed with formula or other breast milk substitutes (56).
“Human milk” is a more specific term than breast milk, as milk from all
species is produced by the breast (3). We use “human milk” and
“breast milk” interchangeably, noting that “human milk” is more
accurate whereas “breast milk” is more conventional.
1There are many terms used in the field of infant feeding, some of which have been
used interchangeably or inconsistently (209). We have made explicit our use of the
most common infant feeding terms in this manuscript; however, debate remains
about what terms should and do mean.
Infant feeding and HIV 227
by guest on May 18, 2011
prevent death or HIV infection, as is the concept “HIV-free
Evolution of strategies for risk mitigation
Replacement feeding. The WHO has long championed the
importance of breastfeeding. This is evidenced in numerous
publications and consensus statements, e.g. the Innocenti
Declaration, the Baby-Friendly Hospital Initiative, and the
International Code of Marketing of Breastmilk Substitutes.
In the early 1990s, great emphasis became placed on avoid-
ing MTCT through breastfeeding. To that end, in 1998,
WHO, UNICEF, and UNAIDS issued a series of documents
stating that replacement-fed, HIV-exposed infants were less
at risk of illness and death so long as they had “uninter-
rupted access to nutritionally adequate breast milk substi-
tutes that are safely prepared and fed to them” (52).
Although the importance of breastfeeding was underscored
in the absence of satisfactory substitutes, these guidelines,
together with the plans to conduct several trials of formula
feeding among HIV-exposed infants, were perceived by
many to be a major shift in WHO policy from the decades
of promotion of “breast is best” (53,54).
The WHO introduced the acceptable, feasible, affordable,
sustainable, and safe (AFASS) criteria into their infant feed-
ing guidelines in 2001 (55). They recommended that all
breastfeeding by HIV-infected mothers should be avoided
when replacement feeding was considered to be AFASS. It
was recommended that each mother, with appropriate coun-
criteriawere met (52).Intheabsence ofAFASS, itwas recom-
mended that infants should be EBF “for the first months of
life;” a time at which EBF or any breastfeeding should cease
was not specified.
The 2010 recommendations did not use the AFASS lan-
guage but instead defined in more detail the environmental
(personal, household, and health service) conditions that
make replacement feeding safer (7). They also shift decision-
making away from counselors and mothers. They state that
national health authorities should decide which infant feed-
ing practice will be primarily promoted and supported by
Maternal and Child Health services but that information
about other practices should be made available.
Modified animal milk. Atthe time the 1998recommendation
was issued, the 2 main replacement milks were modified an-
imal milks and commercial infant formula. Modified animal
milk is typically powdered or fresh cow or buffalo milk to
which water, sugar, and micronutrients are added (56). It is,
however, no longer recommended for feeding infants < 6 mo
because of insufficient macro- and micronutrient content,
concerns about the safety of storage, and occult bleeding
that nonhuman milks can cause (7,57). Indeed, data from
the main study of replacement feeding with nonformula
modified animal milks indicated that Indian infants who
were primarily fed modified animal milks had a greatly in-
creased rate of hospital admission than those who were
Commercial infant formula. Commercial infant formula has
been the most frequently discussed and provisioned replace-
ment milk. It has been made available to HIV-positive
mothers for free as part of government PMTCT policy [e.g.
South Africa (59), Botswana (60)], through nongovern-
mental organizations [e.g. Partners in Health programs in
Haiti, Rwanda, Lesotho; UNICEF in 8 African countries (61)]
and as part of numerous research studies.
In industrialized countries, replacement feeding has been
AFASS formost HIV-positive women,and it is nowstandard
practice for women there to feed their infants formula. In-
deed, in the United States, the CDC has recommended since
1985 that HIV-positive women not breastfeed (62), which
they reiterated in 2010 (63). Replacement feeding, together
with ARV medicines and other intensive obstetric prevention
strategies for infected mothers, has undoubtedly contributed
to the very low rates of PMTCT in high-income countries
(64,65). Replacement feeding in low- and middle-income
countries, however, has not yielded the same positive health
outcomes as it has in high-income countries.
Indeed, replacement feeding ensures that HIV is not
transmitted to the infant via breast milk and an initial study
suggested that HIV-free survival was improved with replace-
ment feeding (66). However, the analytical strategy was prob-
lematic, including the assignment of mixed feeders to the
breastfeeding group (67,68) and the results have not been
More recent data from 9 studies in sub-Saharan Africa
suggest that reductions in HIV transmission achieved with
formula feeding are offset by increases in HIV-unrelated
mortality (Table 1 in 69). In short, current data suggests
there is no net benefit of replacement feeding with formula
to HIV-free survival in sub-Saharan Africa, even when for-
mula is provided for free.
Furthermore, the promotion of replacement feeding can
have negative health consequences for infants who are not at
risk of vertical transmission. Because there is no (further)
risk of vertical transmission, HIV-positive babies should
not be fed replacement milks. However, the promotion of
replacement feeding to HIV-positive mothers can result in
HIV-infected infants not receiving breast milk (38). As for
HIV-unexposed infants, the promotion of replacement feed-
ing has led some women who do not know their status to
opt not to breastfeed for fear of infecting their infant (70);
this has been termed the spillover effect (71; M. Latham
and P. Kisanga, unpublished data).
In addition to detrimental health consequences, replace-
mentfeeding has had negativeeconomic, social,and reproduc-
tive consequences for some infants and mothers. A major
burden of replacement feeding is the expense. In 2009, a 6-mo
supply of formula had an estimated cost of $174; this figure
does not include the cost of clean, safe water or the time to
prepare it (7; Annex 8). This expense is beyond the reach of
the many individuals and governments in the areas where
the majority of MTCToccurs, namely sub-Saharan Africa.
The social consequences of replacement feeding have also
been staggering. In places where breastfeeding is common
228Young et al.
by guest on May 18, 2011
and expected, a woman’s use of other feeding modalities fre-
quently flags her as HIV-positive to both family members
and the community at large (72–74). This can have serious
consequences for the mother-infant dyad, e.g. divorce, os-
tracization, and abandonment of the child. All of these po-
tential consequences, in turn, can dramatically change the
economic calculus associated with decisions related to child
feeding and care, e.g. ostracized women may lose traditional
employment options or their asset bases and hence may
choose not to participate in PMTCT programs, perhaps to
safeguard the futures of children not affected by HIV. Re-
placementfeeding has also had unintended reproductive con-
sequences, because the absence of lactational amenorrhea can
lead to unintended pregnancies (9,11,43) and consequently
an increased number of HIV-exposed infants (60,75).
In conclusion, formula feeding in low-income settings
often leads to serious negative health, economic, and social
consequences for both child and mother and when formula
has been provided in real-world conditions, HIV-free sur-
vival rates have generally been worse (38).
Breastfeeding. EBF. In 1999, Coutsoudis et al. (76) re-
ported the striking finding that the risk of MTCT transmis-
sion with EBF was significantly lower than that associated
with mixed feeding. In 2001 they reported that cumulative
probability of HIV detection in infants was similar for babies
never breastfed and those EBF (0.194), whereas the risk of
HIV infection in infants fed breast milk and other foods
was much higher (0.261) (77). The greatly elevated risk of
MTCTassociated with mixed feeding and the protective ben-
efits of EBF were subsequently demonstrated in other studies
(35,51,78–80). Furthermore, lower non-HIV morbidity and
mortality rates are observed among HIV-exposed, EBF in-
fants compared to their mixed fed counterparts (79,81).
The mechanisms by which EBF is associated with lower
MTCT are not fully understood. They are likely numerous
and have been described at length elsewhere (35,82). Briefly,
EBF may promote maintenance of the integrity of the in-
fant’s gastrointestinal barrier, which is thought to be the
primary mode of infection. The immunological factors in
breast milk likely reduce viral activity in human milk. Addi-
tionally, EBF maintains the integrity of the mammary epi-
thelial lining and promotes overall breast health. For all these
reasons, the 2010 Guidelines recommend 6 mo of EBF in
the absence of AFASS replacement feeding.
Abrupt cessation of breastfeeding. Because of the relatively
low risk of HIV transmission during EBF compared to mixed
feeding, it was thought that abrupt cessation of breastfeeding
might offer infants the maximum health benefit with mini-
mum risk. However, the sole randomized trial to investigate
the effects of abrupt weaning (defined as “as soon as possi-
ble;” 68.8% weaned within 2 d) indicated that the health
risks of rapid weaning (e.g. higher viral load in milk with
abrupt weaning, inadequate nutritional intake thereafter,
death) outweighed the health benefits of PMTCT (51,83,84).
Data from a number of other studies also support these
findings (45,46). Women are now advised to stop breast-
feeding gradually within a month (7).
Another change in the 2010 guidelines is the recommen-
ded duration of breastfeeding in the absence of AFASS con-
ditions. The recommended duration of breastfeeding for
HIV-exposed infants is slowly approaching that for the gen-
eral population. Women are now encouraged to breastfeed
for a minimum of 12 mo and breastfeeding “should then
only stop once a nutritionally adequate and safe diet without
breastmilk can be provided” (85). Although the risk of HIV
transmission continues for as long as breastfeeding con-
tinues (32), HIV-free survival of HIV-exposed infants who
breastfed beyond 6 mo was similar to that of infants who
received no breast milk after 6 mo (86,87). Infants given re-
placement foods after a period of breastfeeding also suf-
fered increased serious infections, including diarrhea and
pneumonia, growth faltering, and death (45–47,50,51,58).
The importance placed on maximizing an infant’s continued
access to breast milk in the 2010 recommendations reflects
the immunological benefits of breast milk as well as the im-
portance of breast milk in providing adequate nutrition to
infants > 6 mo of age.
Wet nurses. Previous iterations of infant feeding guidelines
have discussed 3 modalities by which HIV-exposed infants
may be fed HIV-free breast milk: wet nurses, milk banks,
and mother’s own expressed, heat-treated breast milk (88).
Although wet nursing can ensure that an infant receives fresh
breast milk, it presents challenges of its own, including mak-
ing certain that the wet nurse remains HIV-negative and is
available to feed the infant on demand. Presumptively, be-
cause of these challenges, wet nurses are not discussed in
the 2010 guidelines. Wet nurses are extremely rare (89) and
there is little evidence of HIV-positive women using them
in high- or low-income countries.
Human milk banks. Human milk banks have provided donor
milk for infants for over 100 y; the first milk bank was estab-
lished in Vienna in 1909 (90). Milk banks have long been an
important source of safe breast milk for vulnerable infants,
such as those who are preterm, low birthweight, severely mal-
nourished, orphaned, or born to HIV-positive mothers (91).
When HIV was discovered in breast milk in the early 1980s,
the safety and acceptability of human milk banking was
questioned (92). However, human milk banks use Holder
pasteurization (62.58C for 30 min) to eliminate viral and bac-
teriological contaminants (93) such that there is little risk of
HIV infection from banked milk. Indeed, the health benefits
and long-term cost effectiveness of providing donor milk for
vulnerable infants have been well characterized (94,95).
The WHO endorsement of human milk banking has re-
mained consistently positive (96): “Where it is not possible
for the biological mother to breastfeed, the first alternative,
if available, should be the use of human breastmilk from
other sources. Human milk banks, therefore, should be made
available in appropriate situations.” And in 1992, the WHO in-
cluded donormilkasanacceptable feeding alternativeforHIV-
positive mothers (97,98).
Infant feeding and HIV229
by guest on May 18, 2011
Milk banking is not very common in general and it is ex-
tremely limited in most low-income countries. There is one
exception: Brazil. Human milk banking began there in 1943
and has grown to become the widest breast milk bank net-
work in the world. The Brazilian National Network of Hu-
man Milk Banks has 192 banks and is organized from the
national to the local level, even including firemen who col-
lect milk from donors’ homes (99–102). Recognized interna-
tionally as a model system, the WHO awarded the Brazilian
National Network of Human Milk Banks the Sasakawa Health
proving their nation’s health and reducing infant mortality
In high-income countries, some HIV-positive mothers
feed their infants with banked human milk. Although banked
human milk is more expensive than formula [e.g. ~$3/oz
(29.5 mL) in the US], some insurance companies, including
public insurance plans for low-income women, cover the cost if
there is a maternal or infant indication. Several Web sites also
offer breast milk of unverified safety and origin for sale or
donation. The number of HIV-positive mothers feeding
their infants human milk from either source is not known.
Breast milk pasteurization. Because of the importance of
breast milk to young children and the lack of alternatives in
low-income settings, efforts have been shifting toward miti-
gating the risk of MTCT by making a mother’s own breast
milksafer.Thereare 2methodsfordoing so thatare currently
implementable; one is breast milk pasteurization, the second
is extended ARV use (discussed in the next section).
Pasteurization can occur through a variety of techniques.
Holder pasteurization (62.58C for 30 min), the pasteurization
technique used by most milk banks, is not possible in most
homes, although a single-bottle Holder pasteurizer has been
developed (103). Several other pasteurization methods have
been suggested for in-home use. These include outright boil-
ing of expressed breast milk (104), Pretoria pasteurization (a
jar of expressed breast milk is placed in water that has been
brought to a boil immediately after removal from the heat
source) (105), and Flash-heat (a jar of expressed breast milk
is heated in a pan of water until the water boils and then
the jar is removed from the water and heat source) (106). Re-
inactivate HIVand bacteria in breast milk (107,108) while re-
taining the majority of its nutritional, immunological, and
antimicrobial properties (108–110). Pretoria and Flash-heat
pasteurization preserve nutritional and immunological prop-
erties of milk better than breast milk boiling does, and the
Flash-heat technique may be superior to the Pretoria method
at inactivating viral activity (106).
In the 2001 WHO guidelines, heat treatment of expressed
breast milk was one of the main options (along with EBF and
replacement feeding) to be explained in counseling sessions
with HIV-infected women. It is worth noting that the guide-
lines were never explicit about which technique to use for
heat treatment. After 2006, heat-treated breast milk was no
longer considered a main feeding option but rather one that
may only be AFASS for a select group of women. This rec-
ommendation was likely made based on the unavailability
of population-level studies of the methods. The 2010 guide-
lines listed feeding expressed, heat-treated breast milk as a
possible “interim strategy” in 4 situations: 1) for low-birth
weight or sick infants unable to suckle; 2) for mothers tem-
porarily unable to breastfeed due to illness or mastitis; 3) to
assist mothers to stop breastfeeding; and 4) in situations in
which ARVare temporarily not available (the age of infant is
not specified, i.e. it isnot clear if heat-treated breastmilk was
recommended during EBF or only once complementary
feeding had begun). Home pasteurization was not recom-
mended for extended replacement feeding.
Of the 4 situations listed in the 2010 WHO recommenda-
tions during which heat-treated breast milk can be a possible
interim strategy, the most is known about its use during the
period of transition from EBF to complementary feeding.
Field research from South Africa (111), Tanzania (112,113),
and Zimbabwe (114) has indicated that Flash-heating breast
milk is feasible, i.e. it can be accomplished by women in
low-income households in rural sub-Saharan Africa during
the transition from EBF to complementary feeding.
In Zimbabwe, withweekly home visits from nurses, HIV-
infected mothers of HIV-exposed, uninfected children 6–12 mo
old could safely express and heat-treat breast milk for long pe-
a higher proportion of energy from expressed and heat-treated
milk compared with complementary foods showed more im-
provement in weight and length (114). In a study in Tanzania,
more than one-half of HIV-infected mothers with HIV-
uninfected children that were counseled by community
health workers on the option of expressing and heat-treating
their milk upon the introduction of complementary foods
chose to do so at least once; the median volume of breast
milk pasteurized was 300 mL/d for a median duration of
9.7 wk (1 d to 12 mo) (C. J. Chantry, S. L. Young, W. Rennie,
M. Ngonyani, C. Mashio, K. Israel-Ballard, J. Peerson,
M. Nyambo, M. Matee, D. Ash, K. Dewey, and P. Koniz-
Booher, unpublished data). Furthermore, in Rwanda, a pro-
gram supported by the Ministry of Health is underway to
evaluate the inclusion of Flash-heat training and support
within a comprehensive fortified complementary foods pro-
gram for HIV-exposed infants (115). Preliminary results
from this study suggest that integration of heat treatment
counseling and support is possible at the PMTCT program-
Despite the promising laboratory and feasibility data, the
WHO expert committee declined to recommend in-home
breast milk pasteurization except as an interim strategy, cit-
ing the need for more data on scalability, sustainability,
and health system requirements for supporting breast milk
ARV prophylaxis during breastfeeding. In low-income set-
tings, ARV have been used to reduce the risk of prenatal and
peripartum transmission for more than a decade (116). The
mainstay of ARV prophylaxis for PMTCT in most countries
230 Young et al.
by guest on May 18, 2011
has been single-dose nevirapine (sdNVP), a regimen that con-
sists of a maternal dose intrapartum and an infant dose within
72 h postpartum. Indeed, the testing, counseling, and ARV
provided by these PMTCT programs are largely responsible
for the steady decrease in the incidence of pediatric (<15 y
old) HIVover the past decade from 800,000 in 2001 (117) to
period, however, is relatively new, and is an exciting area for
In the 2010 guidelines, the WHO recommended that all
pregnant, HIV-1–infected women with CD4+ T-cell counts
of #350 cells/mm3initiate lifelong, highly activated antire-
troviral therapy (HAART) for their own health (118). These
guidelines also recommended that ARV be administered
prophylactically to pregnant women with CD4+ T-cell
counts > 350 cells/mm3; the recommended regimen is either
a 2-drug regimen (antepartum azidothymidine (AZT) plus
intrapartum nevirapine) or HAART, which is a combination
of at least 3 ARV.
After delivery, it is recommended that women receiving
HAART (either for their own health or to prevent HIV
transmission) continue on ARV throughout the breastfeed-
ing period and that their infants receive nevirapine for 6 wk.
Those women on HAART for their own health should con-
tinue on ARV indefinitely. Those women on HAART as
HIV-transmission prophylaxis should continue ARV until
1 wk after weaning. Those infants born to women who re-
ceived antenatal AZT/intrapartum nevirapine should receive
daily nevirapine until 1 wk after cessation of breastfeeding.
The decision of who should receive the ARV (the mother
or the child) is left to national governments.
At the time these recommendations were written, these
recommendations are based on strong evidence from clini-
cal trials that ARVinterventions for infants and mothers sig-
nificantly reduce HIV transmission through breastfeeding
(119), with little evidence of diminished protection over
time, no evidence of significant drug-related adverse events,
and no increased adverse events with prolonged ARV
intervention. Studies in Malawi (BAN, DREAM) (120),
Mozambique (DREAM) (121), Tanzania (Mitra) (122), Kenya
(Kesho Bora) (123), and Botswana (Mma Bana) (124) have
all observed low rates (<5%) of HIV transmission (via all
routes combined, i.e. intrauterine, intrapartum, and postpar-
tum) in breastfeeding women receiving therapeutic regimens
initiated during pregnancy and then continued thereafter in
the context of a scientific study.
Datawere available on the protective effects of maternal or
infant prophylaxis up to 6 mo of age, but mathematical mod-
eling suggested 12 mo of prophylaxis provides an optimal
health risk:benefit ratio with regard to HIV-free survival,
and thus the recommendation for duration of ARV provision
was 12 mo (7). The 2 critical assumptions in making this rec-
ommendation are that the efficacy of ARV against transmis-
sion via breastfeeding continue beyond the first 6 mo of the
child’s life under “real life” conditions, and feasibility and ad-
herence with ARV intervention are possible beyond the 6-mo
period to which the clinical trials were limited.
Coverage of ARV prophylaxis. In 2009, 53% (40–79%) of
pregnant women living with HIV in low- and middle-income
countries received any ARV (either sdNVP or combination
regimens) (125). This represents an increase in coverage of
ARV from 45% (37–57%) in 2008 and 15% (12–18%) in
2005 (126). Prophylaxis coverage among the 1.4 million in-
fants born to women with HIV has also increased between
2008 and 2009, but only slightly, from 32% (26–40%) to
This steady increase in coverage represents real progress
toward the reduction of MTCT, but clearly, universal access
to ARV (defined as 80% coverage) is not available in coun-
tries with the highest rates of MTCT. Furthermore, coverage
in these statistics included those women who received
sdNVP, which, although much easier to implement in low-
income settings, is not recommended because of problems
with resistance and lower efficacy (125).
Extended regimens, such as those recommended during
breastfeeding, will be difficult to make universally accessible
given the substantial barriers to scaling up, including health-
care worker shortages and insufficient funding (127). The
difficulties of universal coverage are just one of the many
barriers to ARV prophylaxis during breastfeeding. Problems
with consistent supplies, adherence, and acceptability of
ARV use during breastfeeding mean that ARV must not be
the only approach to postnatal PMTCT.
Given the current knowledge about infant feeding and ver-
tical transmission, most policy makers have felt it is safest
for infants in industrialized countries to be replacement
fed (63). In contrast, ARV prophylaxis while breastfeeding,
6 mo of EBF, and a minimum of 12 mo of any breastfeeding
is currently considered the safest infant feeding modality in
low-income settings (7). Although these recommendations
are based on the results of several decades of enormous re-
search efforts, the fact that 430,000 new cases of pediatric
HIV occurred in 2008 suggests that there remains a great
deal of work to be done by researchers working in the bench,
clinical, behavioral, and implementation sciences. Below, we
outline 2 perspectives, contextualization and holism, that
should be applied to studies of infant feeding interventions
for more informative evaluation and effective implementa-
tion. From this foundation, we describe a variety of basic,
clinical, behavioral, and programmatic research topics that
we expect will lead to a substantial reduction in postnatal
MTCT in low-income settings.
Perspectives for future infant feeding interventions
Contextualizing infant feeding in the cascade of PMTCT
events. The entire cascade of PMTCT events is relevant to
those interested in infant feeding, because a woman who is
unaware that she is infected will not have access to PMTCT
services, including advice on prevention of postnatal MTCT.
Therefore, efforts to reduce vertical transmission must begin
well before an infant is born; they must start by maximizing
the number of infected mothers who receive comprehensive
Infant feeding and HIV 231
by guest on May 18, 2011
PMTCT services. PMTCT services involve many steps, each
of which can become a stumbling block to the reduction of
disease transmission (Table 2).Indeed, recent data has made
clear that the number of women who receive adequate
PMTCT care drops off substantially at each step (125,128).
HIV testing. The initial step in the cascade, learning one’s
HIV status, is a multi-faceted process that can fail at numer-
ous points. A woman must attend a clinic that has PMTCT
services available, be offered a test, agree to be tested, and
then receive the results. PMTCTservices are limited in cov-
erage, although they are rapidly expanding. To increase the
quantity and quality of PMTCTservices, performance-based
financing has been proposed. Performance-based financing
involves offering financial incentives that have the potential
to increase both the quantity and quality of the services that
health-care providers deliver. Performance-based financ-
ing seems to improve HIV service delivery, though data are
limited. For example, improved quantity and quality of
HIV care, treatment and prevention were documented with
performance-based financing in a pilot program supported
by the Elizabeth Glaser Pediatric AIDS Foundation in Ivory
Coast (129). Monetary factors are not the only obstacles to
availability and qualityof human resources for PMTCT; mo-
tivation is related to many aspects of the working environ-
ment (130). For this reason, human resource management
tools like job design, supervision, recognition, continuing
education, career planning, and accountability systems can
effectively increase health worker motivation and perfor-
mance. However, they are not used to their fullest potential
(131,132). Research into the improvement in care given by
the PMTCT cadre is an area that would likely have long-
term beneficial effects on the entire health system, because
PMTCT workers often care for HIV-unaffected segments
of the population as well.
In manycountries, HIV testing and subsequent ARV pro-
phylaxis for PMTCT is provided as part of the Maternal and
Newborn Child Health services and a woman thus must
have at least one antenatal care visit or deliver in the hospital
to enter PMTCTservices. Although overall antenatal care
attendance is high in most countries with the highest HIV
burden, the poorer and more rural populations have less
access to antenatal care, because they are unable to pay for
transport and user fees or cannot afford to be away from
the home for long periods (133). Interventions improving
equity, accessibility, and acceptability of Maternal and New-
born Child Health services will therefore positively affect
PMTCT as well.
With the shift from voluntary patient-initiated testing to
routine (“opt-out”), provider-initiated testing and counsel-
ing in Maternal and Newborn Child Health clinics, the up-
take of testing among pregnant women has been increasing
(132). However, coverage remains far too low to prevent pe-
diatric HIV infection (41). In 2009, only 26% of pregnant
women in low- and middle-income countries received an
HIV test (125). The rates of test coverage were higher in
sub-Saharan Africa (35%), with 50% of women in southern
and eastern Africa being tested compared to 21% in western
and central Africa (125). These numbers do not indicate if re-
sults were received. Test results must be given to the woman
in a timely manner, ideally the same day. The effort that is
typically involved in returning to the clinic several days later
means that some women never learn their status.
Prenatal and perinatal ARV use. Once a woman learns she
is infected, a variety of factors influence if she is offered,
pregnancy, delivery, and breastfeeding. First, a woman identi-
fied as HIV-infected needs to be evaluated to determine if
she is eligible for ARV therapy for her own health. Women liv-
ing with advanced HIV disease not only have an increased risk
of dying, they also have progressively higher vertical and hori-
zontal transmission rates than those with less advanced infec-
tion, because they have higher viral loads. A recent study
calculated that women with CD4 counts < 200 cells/mm3
(the previous WHO cutoff for ARTeligibility) and between
200 and 350 cells/mm3(the current WHO cutoff) had
MTCT rates of 44 and 28%, respectively, whereas MTCT
rates among women with CD4 counts between 350 and
500 cells/mm3and >500 cells/mm3were only 13 and 10%,
respectively (134). Therefore, whether a country applies the
current or the previous WHO criteria, giving a treatment-
eligible woman ARV prophylaxis instead of ARV therapy
means missing an opportunity to reduce the likelihood of
horizontal disease transmission.
Table 2. Potential barriers and motivators to the cascade of
events of PMTCT care1
EventPotential barriers and motivators
Accessibility, fear, and distrust of care
Offered test Stock-out of test supplies, broken
machinery, reliable testing methods
Agree to test Fear and distrust of clinic staff, fear of
disclosure and discrimination by
community, availability of efficacious
Receive resultsAccessibility (if necessary to return to clinic),
availability and training of testing
ARV offered to
mother and babymultiple times to collect infant
medicines), availability of medicines
by mother and babyfear, and distrust of their
efficaciousness, potential for disclosure
and subsequent discrimination, drug
effectiveness and adherence, consistent
availability of medicines
Safer feedingEducation about safest modality, local
beliefs about optimal infant feeding
practices, availability of safe replacement
feeds, support of family to EBF
Infant testedAccessibility (if necessary to return to clinic),
clinic resources, maternal permission.
Accessibility (if necessary to return to clinic
Accessibility (if necessary to return to clinic),
1Adapted with permission from (210).
232Young et al.
by guest on May 18, 2011
Assessment of eligibility for ART is often impossible to
conduct in a Maternal and Newborn Child Health clinic
setting, either because CD4 count testing is not available or
because staff are not trained to perform clinical staging.
Even in health facilities in which both PMTCT and Care
and Treatment services for HIVareoffered, linkages between
the 2 are often weak (135). These factors explain why only
about one-half of the pregnant women who tested positive
for HIV in low- and middle-income countries were assessed
for ART eligibility (133). Stock-outs or expiration of ARV
drugs may be other impediments to timely initiation of
the prophylactic or therapeutic ARV regimen (136,137).
Uptake of the infant’s ARV dose(s) is influenced by sim-
ilar availability, accessibility, and acceptability factors as
those affecting the uptake of the mother’s dose(s), but
with the added complication that in some countries only in-
fants of mothers delivering in the facility or who are brought
to the facility within 72 h after delivery get the postpartum
sdNVP dose. Because institutional delivery rates are usually
well below antenatal care attendance rates, and because re-
turning to the health facility soon after homebirth may be
uncomfortable and may also require money and careful
planning, coverage of prophylaxis is much lower for infants
than for mothers (125).
Holistic evaluations of PMTCT interventions. PMTCT
interventions, postnatal and otherwise, will be better under-
stood and therefore more effective if they are evaluated more
holistically, i.e. in terms of their psychosocial and economic
consequences as well as their biological ones. Much of the
research on postnatal PMTCT to date has focused solely
on the biomedical consequences of infant feeding modali-
ties, primarily disease transmission and survival. Yet the
spectrum of strategies for reducing MTCT has frequently
come with a range of unintended and often unmeasured
psychosocial ramifications, from unintended disclosure to
physical abuse, rejection by partners, ostracization by fami-
lies, and abandonment of infants. Thus, we recommend that
regular feedback and open-ended evaluation by study or
program participants and staff occurs throughout the course
of the intervention to gauge psychosocial consequences.
Moreover, these studies should also involve individuals who
choose not to participate in PMTCT programs.
Similarly, the magnitude and timing of private costs (in-
dividual and household-level expenses), public sector costs
(those paid for by the national government), and civil society
costs (those paid for by international organizations, nongov-
ernmental organizations, local volunteers, etc.) of interven-
tions to HIV-affected persons is another component of
PMTCT interventionsthathasfrequently beenoverlooked.In-
dividual costs include opportunity costs, such as income fore-
gone while traveling far distances to clinics or waiting in long
lines for care, as well as expenditures required to adhere to rec-
to facilities, and to buy replacement milks for infants. The
economic consequences of participating in PMTCT pro-
grams and adhering to prescribed recommendations have
also received little attention. Families may sell assets to pay
for care, HIV-positive women may engage in transactional
sex to pay for formula for their infants, and governments
may reappropriate funds from other programs to fund the
purchase of formula and medicine or the training of health
care workers. These consequences are not sufficiently docu-
mented in most analyses.
These costs will influence not only the willingness and
ability of women to participate in PMTCT programs but
also the amount of time they spend in programs and the
degree to which they adhere to program recommendations.
Therefore, we recommend that a household-level focus be
adopted for economic analyses, that careful consideration
be given to the economic and other risks to women and
to their children (HIV-positive and other) of participating
in MTCT programs, and that the likely inherent selectivity
biases associated with studying only those women who par-
ticipate in such programs be carefully addressed.
The measurement of programmatic costs (public sector
and civil society) should include the cost of the purchase
and distribution of medicines and foods and the burden
to health care personnel that increased testing and counsel-
ing on HIV, optimal infant feeding, and ARV represents.
Desmond et al.’s (138) work on infant feeding counseling
in South Africa is exemplary and rare for its cost analyses.
With data on these costs in hand, sound costing and cost-
effectiveness calculations will be possible.
In addition to evaluating what are sometimes referred to
as downstream factors or the outcomes of a program or in-
tervention, i.e. the adoption of as well as adherence to rec-
ommended behaviors, PMTCT interventions must also
pay attention to the delivery side, i.e. program coverage
and the quality and consistency of implementation (139).
It is important to ascertain the extent to which these inter-
ventions are delivered as intended, an endeavor that entails
paying attention to and measuring factors such as training
effectiveness, quality of supervision, motivational character-
istics of frontline workers, and quality of contact between
health care worker and client.
Finally, as promising interventions are developed, tested,
become recommendations, and are rolled out, it is critical to
bear in mind that the majority of MTCT occurs in sub-
Saharan Africa. Indeed, in 2008, the majority (91%) of
new infections among children occurred in sub-Saharan
Africa, with the bulk of these occurring in southern and
eastern Africa (31). It is also worth noting that transmission
isdisproportionately high, given that only 67% of people liv-
ing with HIV worldwide live in sub-Saharan Africa (31). The
unique agro-ecological and cultural circumstances of sub-
Saharan Africa must be borne in mind as interventions are
evaluated and as research priorities and public health poli-
cies are set. Although the enormous cultural diversity within
sub-Saharan Africa must not be overlooked, it is fair to ac-
knowledge the setting is distinct from middle-income coun-
tries or even other low-income regions of the world. These
circumstances include particular environmental (e.g. poor
access to adequate sanitation, limited availability of clean
Infant feeding and HIV233
by guest on May 18, 2011
water, reliance on subsistence farming), cultural (e.g. socie-
tal expectations to breastfeed, importance of extended fam-
ily in raising infant), disease (e.g. high prevalence of malaria
and intestinal parasites), and economic (e.g. cash-strapped
public health programs, high prevalence of food insecurity)
considerations, which must be taken into account when
viable interventions are considered. Because of cultural and
ecological variation, all interventions must include qualita-
tive, formative research prior to implementation, such as
that done in the BAN study in Malawi (140).
In summary, a holistic, contextualized understanding of
the biological, psychosocial, and economic consequences
of PMTCT strategies is critical for determining their real-
world implementability, effectiveness, and sustainability.
Furthermore, these consequences need to be considered
not just for the mother or the health care system but in
the context of the household and community in which the
HIV-exposed infant is raised. For example, are community
members supportive of EBF? And if not, why? How can
mothers strategically navigate barriers to EBF? Is it culturally
acceptable to give newborns nevirapine syrup for a pro-
longed period of time? Does the mother need to conceal
this behavior? Can she enlist family member support, e.g.
others reminding her to administer it or acquiring more
from the clinic? Tonwe-Gold et al.’s (141) evaluation of
family-focused HIV care in Cote d’Ivoire is exemplary in
its consideration of the family as the unit for PMTCT.
Similarly, the presence and welfare of other children in
the household must be considered. The literature to date
has tended to focus very narrowly on the infant and his or
her HIV-affected mother. Although this focus may be ap-
propriate for single-child households, it is probably inap-
propriate for households with multiple children in which
the welfare of siblings must be considered when making de-
cisions about care sought by HIV-positive mothers and the
infant feeding practices they adopt.
Given the need for a holistic evaluation, research on the
prevention of postnatal HIV transmission is an endeavor
that must engage and involve a multitude of international,
government, private, programmatic, advocacy, and research
groups. Large-scale international initiatives to prevent MTCT
include the President’s Emergency Plan for AIDS Relief, the
MTCT-Plus Initiative (Columbia University), the Global
Fund, the Call to Action project (Elizabeth Glaser Pediatric
AIDS Foundation), the UN Interagency Task Team on
MTCT, and the USAID flagship project on infant and young
child nutrition (previously the LINKAGES project, currently
IYCN). Donor support for multi-sectoral interventions,
such as those that simultaneously address infant feeding
and vertical transmission, could fuel some very effective
partnerships. Currently, such alliances are limited in their
appeal to funders. However, the Feed the Future and Global
Health Initiatives, both of which have recently been
launched by the U.S. government and aim to curb malnu-
trition and improve maternal and child health in a very
comprehensive way, suggest that attitudes toward multidis-
ciplinary interventions may be changing.
Infant feeding topics for future research
Future research into postnatal PMTCT is urgently needed in
a number of domains: extended postnatal ARV prophylaxis,
EBF, counseling, breast milk pasteurization, breast milk
banking, novel techniques for making breast milk safer, and
other optimal breastfeeding practices. There are basic, clin-
ical, behavioral, and programmatic types of questions that
need answers within each of these domains.
Extended postnatal ARV prophylaxis. The 2010 WHO
recommendations for ARV to be used prophylactically to
prevent MTCT during breastfeeding mean that research
on their use is a pressing priority. Very little is known about
the implementation or biological, economic, or social con-
sequences of extended prophylactic ARV for PMTCT in
real world settings; all data to date are from carefully con-
ducted clinical trials.
At the time of writing, only a few countries (59) have de-
termined their postnatal ARV policies in light of the 2010
recommendations, i.e. if ARV will be given to mothers or
infants, and if it is to mothers, what that regimen will be
and the duration of provision. Once the policies are imple-
mented, it will be beneficial to describe the various imple-
mentation strategies. Will ARV support be integrated into
general infant health programs? Or will it remain in
PMTCT services? Will it be rolled out by peer counselors
or by highly-trained medical staff? Will women be given
the medicines they will require postnatally prior to deliv-
ery, e.g. the Mother-Baby pack (142)? An analysis of the
strengths and weaknesses of the different implementation
approaches from biomedical, psychosocial, and economic
perspectives will help identify the most effective imple-
mentation strategies for prophylaxis during breastfeeding.
Depending on the distribution of alternative policies that
are adopted and the characteristics of programs and target
populations, a natural experiment capable of clearly iden-
tifying the most effective and cost-effective approaches
could present itself.
There is also much to learn about the biological conse-
quences of extended ARV prophylaxis. For example, there
are little available data on prophylaxis during 12 mo of
breastfeeding. And although we have 15 y of data on ARV
use in the prenatal and peripartum (to 6wkpostpartum) pe-
riods, we know very little about the safety of prolonged ex-
posure to ARVearly in life or of repeated courses of HAART
in women not requiring the medicine for their own health
(41). Also pressing are consequences for drug resistance
(41,143). Other consequences to consider are those for lac-
togenesis; to our knowledge, there has been no study of the
effect of ARVon the quality or quantity of breast milk pro-
duction. It will also be useful to compare health outcomes
for mothers and children in countries that have chosen
maternal prophylaxis with those that have chosen infant
prophylaxis. Given that available data suggest the effica-
ciousness of both regimens is comparable for rates of HIV-
free survival, major differences in maternal health outcomes
could influence subsequent recommendations.
234Young et al.
by guest on May 18, 2011
The behavioral consequences of extended ARV prophy-
laxis are currently unknown. What will adherence be? Will
it be higher in pregnant populations than in the general pop-
ulation? Will the heightened sense of smell and increase in
nausea and vomiting (morning sickness) during pregnancy
render ARV medicines intolerable? Will mothers understand
the function of prophylactic ARV? In Malawi, e.g., some
mothers thought that sdNVP protected their infant through
6 mo of breastfeeding, and others thought that co-trimoxazole
prophylaxis (an antibiotic) prevented postnatal transmission
of HIV (144). Will ARV prophylaxis make EBF seem less im-
portant with a concomitant increase in mixed feeding?
Even less is known about the social consequences of ARV
during breastfeeding. ARV prophylaxis involves a higher
number of pills being consumed more frequently, which
has implications for voluntary and involuntary disclosure
and subsequent stigma. It is also important to know if the
use of ARV prophylaxis causes any other unanticipated stigma,
e.g. HIV-exposed babies become regarded as HIV-positive
Once they no longer qualify for prophylaxis or therapeu-
tic treatment, how will mothers choose to feed their infants?
Will they continue to breastfeed from the breast? Will they
pasteurize their breast milk? What happens to the mother’s
health and her and her family’s ability to care for her child
(ren) after she stops ARV?
Finally, inadequate coverage remains a critical issue for
ARV use. Given that in 2009, only 53% of pregnant women
living with HIV in low- and middle-income countries re-
ceived any ARV (either sdNVP or combination regimens)
(125), there is a staggering amount of work to do. Both
the number of women and infants who receive ARV as
well as the duration for which they are now recommended
to receive them has greatly increased without a commensu-
rate increase in health care workers or funding.
The removal of barriers to EBF. Current rates of EBF are
well below targeted levels in both HIV-affected and unaf-
fected populations around the world. Increasing rates of
EBF is one of the most powerful interventions to save child
lives; the promotion of breastfeeding could prevent 13–15%
of child deaths in low-income countries (1). Other benefits
of the promotion of EBF include that it is also a healthful be-
havior for HIV-unexposed infants and their mothers, is
helpful for birth spacing, requires minimal preparation, is
not dependent upon outside materials, and breast milk
does not need purchased. Additionally, the fact that breast-
feeding is a common behavior means it is unlikely to flag the
mother’s HIV status.
Although there are many advantages of EBF, a woman’s
initial decision to EBF can be stymied by a range of societal,
household, and individual factors. At the individual or
household levels, poverty is a risk to EBF when women
need to return to income-generating activities (145). Percep-
tions at the community level that breastfeeding always leads
to HIV infection in the infant have dissuaded some women
from EBF (146). At the macro-level, women from across the
entire socioeconomic spectrum are thwarted in their efforts
to EBF by well-meaning community members who insist
that it is not appropriate. They may suggest that colostrum
is harmful (147), that the infant is not getting all the nutri-
ents and or liquid she needs from breast milk alone (148), or
that formula is somehow superior (149). Women themselves
may decide they are unable to EBF because of either per-
ceived or actual (which is uncommon) insufficient milk pro-
duction (148,150); in low-income settings this is frequently
associated with perceived inadequate nutritional intake
An additional barrier to EBF is misunderstanding what it
is; women may think they EBF when in fact they do not. In
Malawi, e.g., mothers did not understand that feeding warm
water to infants was in conflict with EBF; it was done to pre-
pare the infant gut “so that the intestines can open up” (144).
In summary, any efforts to increase EBF must first focus
on local community expectations about infant feeding for all
women as well as experienced and perceived barriers to EBF.
They must also consider women’s own perceptions of the
consequences of breastfeeding when infected with HIV
(144,153). Only once the reasons for not EBF are identified
should approaches to increasing rates be implemented.
There are a variety of interventions for improving rates of
EBF, from education to cash transfers to mass media mes-
sages (154); the application of these to HIV-infected popu-
lations or general populations in countries with high HIV
prevalence will be informative. Similarly, the evaluation of
the high-priority strategies for protecting, promoting, and
supporting EBF detailed in the Global Strategy for Infant
and Young Child Feeding (155) would be useful in the con-
text of HIV.
PMTCT counseling. So far, we have discussed both the
enormous health benefits and the numerous potential bar-
riers to both extended drug regimens and EBF. Serendipi-
tously, the 2 practices share a proven way to increase them:
Although counseling has been proven effective, there is a
dearth of high-quality infant feeding counseling material
(156–159) and HIV counselors (for testing or for HAART)
(160), in part because there are insufficient numbers of
health care workers, especially in sub-Saharan Africa (160,
161). Indeed, the shortage of health care workers is a major
obstacle to the scale-up of PMTCT services (127). For this
reason, increases in coverage and quality of PMTCTservices
will likely require innovative staffing strategies among health
care professionals, including shifting tasks from professional
health workers to nonprofessionals (132). Studies of the
cost-effectiveness of counseling-based strategies would also
Peer counseling, i.e. counseling by community members
who are not biomedically trained, has been demonstrated to
be highly effective at increasing the rate of EBF in both HIV-
negative (162–164) and HIV-positive (165) women through
clinic-based and home-based counseling (166). Trained
community-based treatment supporters have also increased
Infant feeding and HIV235
by guest on May 18, 2011
patient satisfaction and adherence in HIVand TB treatment
programs (167–169). Unfortunately, the role of counseling
has sometimes been overlooked as a strategy for PMTCT
(170) and as such, far less research has been done evaluating
its effectiveness in terms of health outcomes or cost than has
gone into biomedical interventions.
Indeed, very little is known about the effect of using peer
supporters, including mothers, grandmothers, traditional
birth attendants, or other people living with HIV/AIDS in
the prevention of vertical transmission. Futterman et al.
(171) concluded that in a South African program deploying
peer mentor mothers, medical follow-up visits to the
PMTCT clinic increased as did knowledge about PMTCT.
In India, the introduction of peer counselors resulted in a
6-fold increase in the percentage of HIV-positive women re-
ferred for care and more than doubled the institutional de-
livery rates (133). Additionally, promotion of infant feeding
buddies, similar to ARTadherence buddies, is currently be-
ing investigated in one South African PMTCT program as
another mechanism of providing home- or community-
based support for mothers to safely feed their infants. We
do know that there is insufficient counseling in current
PMTCT programs (136,172,173). Community supporters
may be essential in helping mothers to access services and
adhere to guidelines, especially because current PMTCTser-
vices and care are shown to be particularly poor in the post-
natal period (174,175).
Even less is known about the role of peer counselors to
support prophylactic ARV use. We do not know if women
would welcome support to take (or administer) prophylactic
ARV, and if they would, what the optimal messages and fre-
quency of contact would be. Furthermore, because there
have been no studies of the effect of peer counselors on pro-
phylactic ARVadherence, we do not know the effect of such
an intervention. Given recent efforts to respond to the 2010
guidelines, such a study would be extremely informative; the
inclusion of cost-effectiveness evaluation would be invalu-
able for program planning.
Finally, it likely would be beneficial for all counselors to
have standardized counseling materials, similar to what
the Tanzanian Ministry of Health has adopted for infant
feeding counseling in the context of HIV/AIDS (176).
Such materials may help to mitigate some of the frustration,
confusion, and misinformation that accompanies imple-
mentation of changes in guidelines (177).
The role of disclosure in adherence to PMTCT guidelines.
A woman’s social, economic, and cultural context may well
be predictive of her acceptance of PMTCT care, including ad-
herence to ARV and likely infant feeding behaviors. Many
PMTCT counselors encourage women to disclose their HIV
status to at leastone person, usually a householdmember, be-
cause of its reported benefits of reduced anxiety, more social
support, increased access to services, increased opportunities
for prevention of transmission to sexual partners, increased
ARV adherence, and better planning for the future (178,179).
However, fear of stigma, discrimination, and blame by
community or family members, partner violence, abandon-
ment, and loss of personal or household assets or of eco-
nomic opportunities may cause women to not want to
know or disclose their status and shun PMTCT services
(180–183). It stands to reason that disclosure may similarly
affect her ability to adhere to recommended infant feeding
practices, although currently very little is known about
this (184). The consequences of disclosure to community
members (i.e., those other than her partner) to achievecom-
munity support for adherence to ARV prophylaxis and in-
fant feeding practices needs further exploring (185). Lastly,
tools to identify women at higher risk for negative outcomes
of disclosure need to be developed and tested (178).
Disclosure of HIV status has generally been shown to be
beneficial to mothers who choose to do so. Although cou-
ples counseling and facilitated disclosure has been shown
to be feasible and scalable in selected areas (186,187), male
involvement has been disappointing in others (186–188).
Too little is known about what are optimal counseling
scripts, who are the most effective counseling cadres, and
what are the best places and times to assist women in dis-
closing to their partners or in improving partner involve-
ment in PMTCT (189–192).
Breast milk pasteurization. Despite the promising labora-
tory and feasibilitydata, the WHO expert committee declined
to recommend home-based breast milk pasteurization except
for as an interim strategy, citing the need for more data on
scalability, sustainability, and health system requirements
(7). Even when ARV prophylaxis is successfully implemented
for the first months of breastfeeding, MTCT can occur if
breastfeeding continues after the cessation or during inter-
ruptionofARV (193).Thissuggests that methodsto continue
able,refused,or interrupted,orfor womenwhooptto breast-
feed after prophylaxis is discontinued. As such, a large clinical
study of the scalability and of the clinical and socioeconomic
consequences of the method is overdue.
Breast milk banks. Breast milk banking is an underutilized
strategy for the production of safe breast milk. Many indus-
trialized countries have been able to provide donor milk
through intensive commercial-grade pasteurization, but
this has been limited in scope. For example, the United
States Human Milk Bank Association of North America cur-
rently has only 14 functioning milk banks. There are far
fewer milk banks in middle- and low-income countries
(with the exception of Brazil) and the development and ex-
pansion of milk banking has remained a daunting challenge.
Yet atthe same time, milk banks maybe mostneeded in low-
income settings. For example, many children orphaned by
HIV/AIDS are under the age of 5 y and at increased risk
for negative health outcomes, including malnutrition (194).
Such infants would benefit greatly from the rehabilita-
tive and immunological properties of breast milk, such as
that available from a breast milk bank. A community-based
milk bank in South Africa was recently started to provide
236Young et al.
by guest on May 18, 2011
donor milk to HIV-exposed infants in need (195). This
model may be one that could work in other low-income set-
tings; further research on the economic feasibility and sus-
tainability of milk banks in such settings would be very
useful, in part because such studies may shed light on the
role of public policy in promoting and sustaining these
Other techniques for the reduction of vertical transmission.
There are currently several types of research into novel tech-
niques for making breast milk safer. One method involves
chemical treatment of milk. There was some hope that the
antiviral properties of chloroquine might reduce breast milk
viral loads; this, however, has not been the case (196). A pre-
liminary study of treating breast milk with a microbicide,
SDS, has shown some promise in a laboratory setting (197).
To our knowledge, there have been no field studies of this
technique. Nipple shields with an insert that elutes microbi-
cide or ARVare also under development. They are currently
in prototype phase with considerable laboratory and field
studies research remaining (198). Avaccine that couldprotect
an infant from infection would make breast milk from an
HIV-positive woman safer (199). Currently, there are several
results are not yet available.
Another area of development is novel ARV delivery
mechanisms. A number of international organizations have
called for investment in innovative ARV delivery devices
(3). These include dissolvable films, transdermal patches, mi-
crotablets, and injectable ARV. Other ideas are implantable
devices in which ARV medicines are slowly released, akin to
hormonal contraceptive implants. These alternative delivery
systems may be more appropriate for pediatric formulations
and for longer term prophylactic use and would likely be wel-
comed by those using ARV.
Breastfeeding in high-income settings. As additional data
demonstrate the safety of breastfeeding with either maternal
HAARTor infant ARV prophylaxis, it is inevitable that HIV-
infected women in high-income settings will express a desire
to breastfeed their infants (200,201; D. Cohan, unpublished
observations; C. Chantry, unpublished observations). Al-
though HIV-infected mothers in such countries who choose
to breastfeed may be prevented from doing so or even be
charged with child endangerment if they persist (200), there
is growing recognition that breastfeeding may be the only
acceptable mode of infant feeding for some of these women
(202). Clinicians will need to be prepared to help women
make informed decisions about the relative risks of the vari-
ety of feeding modalities. Indeed, the UK Department of
Health advises that “Under exceptional circumstances, and
after seeking expert professional advice on reducing the
risk of transmission of HIV through breastfeeding, a highly
informed and motivated mother might be assisted to breast-
feed” (202). Currently, there isminimaldata onwomen inin-
dustrialized countries who feed infants their own breast milk
[notable exceptions include (201,203)].
It is therefore informative to follow the health status of
high-income, HIV-infected women who opt to breastfeed
their infants, together with the health of their infants. It is
also useful to characterize current infant feeding preferences
among women in high-income settings and to track how
these change as our understanding of PMTCT evolves.
Such predictors of desired infant feeding modality could in-
clude, but should not be limited to: 1) country of origin and
time since immigration; 2) HIV disclosure to partner/family
members/community; 3) time since HIV diagnosis; 4) clin-
ical disease progression; 5) infant feeding experience with
prior children; 6) access to formula/human banked milk; 7)
self-perceived community standards/expectations; 8) experi-
ence with ARV during pregnancy and/or the postpartum pe-
riod; and 9) socioeconomic characteristics of women and the
households in which they live.
Other optimal breastfeeding practices. Although the 2010
guidelines recommend continued breastfeeding to 12 mo
with extended ARV prophylaxis, the optimal duration of
breastfeeding for HIV-exposed infants, i.e. one that balances
the health risks of virus and ARV exposure with the nutri-
tional and immunologic benefits of breastfeeding, is not
yet clear. Environmental factors, such as inadequate sanita-
tion and quality of complementary feeding (204,205), are
sure to modify the risk:benefit ratio, but their effect size in
HIV-exposed populations is currently unquantified. We
also do not know what the relative risk:benefit ratio is for
HIV-positive infants who have consumed nonbreast milk
foods to initiate or resume breastfeeding from their HIV-
infected mother. The differences in risk associated with ver-
tical transmission during mixed feeding vs. complementary
feeding have also not been made clear, because in much of
the HIV literature, complementary feeding has not been dif-
ferentiated from mixed feeding (Table 1). Elucidation of the
basic science behind the mechanisms of transmission would
be immensely useful in answering these questions.
When evaluating optimal duration of breastfeeding, it
is worth considering that the 2010 recommendation of
12 mo of breastfeeding is contrary to the recommended
duration of breastfeeding in HIV-unexposed infants, which
is through the second year of life and beyond (206). The
shorter recommended period of breastfeeding duration
among HIV-positive compared to HIV-negative mothers
may trigger another spillover effect, whereby uninfected
mothers shorten the duration of breastfeeding.
The field of postnatal PMTCT-HIV is experiencing a number
of exciting breakthroughs, which present important opportu-
nities for research and programming to improve the welfare
of HIV-affected women and their children. Recently devel-
oped interventionsand methodswith demonstratedeffective-
ness have the potential to prevent HIVinfection and promote
the growth of healthy infants more effectively than was previ-
biological, psychosocial, and economic consequences. We
Infant feeding and HIV 237
by guest on May 18, 2011
therefore strongly suggest that future research focus on holis-
tic evaluations of these practices in order to help policy
makers choose the most feasible, cost-effective ways to reduce
vertical transmission and promote the development and
growth of children of HIV-positive mothers. Furthermore,
prioritization of research that will increase the coverage of
those interventions with the most promise, especially toward
increasing rates of EBF, ARV coverage, and breast milk pas-
teurization, will certainly maximize the HIV-free thrival of
the next generation of HIV-exposed infants.
This paper is dedicated to the memory and spirit of Prof.
Michael Latham, whose intellectual and humanitarian com-
mitment to the health of mothers and children will be car-
ried forth by the many who knew and loved him. We
thank Werner Schimana for his input during the formative
stages of this manuscript, Anne Williams for sharing useful
references, and Emily Wolfe-Roubatis for her comments on
an earlier draft. S. Young conceived and cowrote all sections
of the paper. M. Mbuya assisted with drafting the outline
and cowrote the sections on program evaluation and breast-
milk pasteurization. C. Chantry assisted with definitions
of breastfeeding and cowrote the sections on benefits of
HIV-free thrival, and infant feeding in high- and low-income
countries. E. Geubbels cowrote the sections on coverage of
ARV prophylaxis and on the contextualization of infant
feeding in the cascade of PMTCT events. K. Israel-Ballard
cowrote the section on breastmilk pasteurization and hu-
man milk banking. D. Cohan cowrote sections on ARV pro-
phylaxis and infant feeding inhigh-income countries. S.Vosti
cowrote sections on costs, economic and otherwise, of infant
feeding decisions. M. Latham cowrote the sections on the
spillover effect and contributed significantly to the outline.
S. Young had primary responsibility for final content. All au-
thors read and approved the final manuscript.
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