Nutrition and HIV
Henrik Friis, University of Copenhagen, Frederiksberg, Denmark
Mette Frahm Olsen, Nordic Cochrane Centre, Copenhagen, Denmark
Suzanne Filteau, London School of Hygiene and Tropical Medicine, London, UK
2017 Elsevier Inc. All rights reserved.
This article is an updated version of the previous edition article by Henrik Friis, Stuart Gillespie, Suzanne Filteau, volume 4, pp. 572578, 2008,
Elsevier Inc.
Introduction
When rst described in Africa, the advanced stage of human
immunodeciency virus (HIV) infection acquired immune
deciency syndrome, or AIDS was called slim disease, due
to the pronounced wasting that is a cardinal manifestation,
especially in individuals with poor dietary intake before and
after being infected.
Sub-Saharan Africa continues to have the highest HIV burden
in the world with well over two-thirds of the 37 million individ-
uals living with HIV infection in 2014. Of a global 1.2 million
AIDS deaths and 2 million new HIV infections in 2014, sub-
Saharan Africa accounted for 0.8 million and 1.4 million, respec-
tively (UNAIDS, 2015). In low-income populations, nutrition
and HIV infection are closely linked at the level of the individual,
the household, and the community. The HIV epidemic is not
driven by poverty per se, but rather thrives in a context of socio-
economic inequality. However, poor individuals are much more
vulnerable to the consequences of HIV infection and its associ-
ated stigma, which may increase the risk of food insecurity.
The consequences of inadequate dietary intake in turn increase
the susceptibility to infection and the progression of disease
and reduce the effects of medical treatment. Thus, food insecu-
rity and undernutrition may be determinants as well as conse-
quences of HIV infection (Figure 1).
Even in high-income populations some patients may not
have a diet meeting the nutritional requirements. This could
be because the health system fails to provide nutritional advice
to the patient, and the patient lacks knowledge or resources to
obtain an adequate diet. Many organizations and Internet sites
provide information on the importance of diet, and people
living with HIV often take nutritional supplements, herbs, or
other complementary food-based therapies, although the
evidence for efcacy and safety is lacking.
Nutrition and Infections
Adequate intake of energy and nutrients is necessary to main-
tain health. The macronutrients (i.e., carbohydrates, protein,
and fat) provide energy and the micronutrients (i.e., vitamins
and minerals) are essential for general and specic metabolic
functions. A diet that is inadequate in energy and nutrients fails
to sustain optimal growth of children and maintain weight and
body composition of adults and impairs specic body
functions.
In low-income populations, the typical diet is often based
on a starch-rich staple, such as cereals or tubers, with legumes,
few vegetables and fruits, and little, if any, animal foods. Such
a diet has a low energy and nutrient density. The bulkiness of
International Encyclopedia of Public Health, 2nd edition, Volume 5
the diet renders it difcult to meet the energy and nutrient
requirements, particularly for children, even if the access to
food is adequate. In addition, the quality of the diet is often
low. Vitamin A, for example, is rarely available as preformed
vitamin A, found in animal foods, but mainly as provitamin
carotenoids found in plant-based foods. The conversion of
provitamin A carotenoids to vitamin A in the body is less ef-
cient than previously believed and further impaired by de-
ciency of other nutrients. Iron is mainly available as the
poorly absorbable nonheme iron from plant sources and rarely
as heme iron from animal foods. Furthermore, the staple foods
contain high levels of phytic acid and other antinutrients,
which bind essential minerals such as zinc and iron and
prevent their absorption. In addition to the low intake and
bioavailability of micronutrients, a high burden of infectious
diseases increases the requirements and considerably contrib-
utes to the high prevalence of deciencies.
Women and children are particularly vulnerable to nutri-
tional deciencies. Since women often have inadequate dietary
intake before and during pregnancy, fetal growth will be
retarded and the child born with low weight and inadequate
nutrient stores. Although exclusive breastfeeding up to
6 months of age is recommended by the WHO, many children
Food insecurityundernutrition HIV infection
al
y
old
nit
du
ivi
eh
mu
Ind
us
m
Ho
Co
Figure 1 The vicious circle due to a synergistic relationship between
human immunodeciency virus (HIV) infection and food insecurity and
undernutrition, at individual, household, and community levels. HIV
leads to nutritional deciencies in the individual and to food insecurity
in the household and community. Food insecurity increases risk of HIV
infection, and undernutrition increases progression of HIV infection.
http://dx.doi.org/10.1016/B978-0-12-803678-5.00306-4 271
272 Nutrition and HIV
receive water, tea, cows milk, porridge, and so on, from the rst
few weeks of life. The combination of early nutritional de-
ciencies and contaminated liquids and solid foods increases
the risk of diarrhea and pneumonia, which further impair the
nutritional status of the child.
Deciencies of vitamin A, iron, and zinc, as well as other
micronutrients, are widespread in low-income populations.
Lack of micronutrients may impair specic body functions,
such as cognitive functions, vision, production of red blood
cells, and immune functions. Some micronutrients have anti-
oxidant (e.g., vitamins C and E, and selenium) or prooxidant
(e.g., iron) properties, which means that they are able to either
counteract or generate, respectively, harmful oxidative stress.
Cheap and feasible public health interventions exist, whereby
the intake of micronutrients, in contrast to macronutrients,
can be increased in populations. These include dietary diversi-
cation, food fortication, food modication, and nutritional
supplementation. In addition, interventions to prevent and
treat common infections serve to prevent further increases in
requirements.
Immune Functions and Resistance to Infections
Immune suppression caused by lack of nutrients has been
called nutritionally acquired immunodeciency syndrome,
or NAIDS. Lack of zinc, of which only about 1 mg is needed
every day to replace losses, leads to virtual disappearance of
the thymus, a key immunological organ. Thus micronutrient
deciencies often increase risk and severity of infectious
diseases. Since infections also impair nutritional status, they
form a synergistic two-way relationship or a vicious circle
(Figure 1). Nevertheless, even if a specic nutritional de-
ciency impairs immunity, administration of that nutrient
may favor the pathogen more than the host especially if
unphysiological doses or routes are used and hence increase
the risk and severity of infectious diseases. For example,
parenteral and even oral administration of iron may stimulate
growth of bacteria or parasites and lead to increased
morbidity. Vitamin A is essential for a range of immune func-
tions, and large randomized trials have found that periodic
administration of vitamin A capsules to children under
5 years reduces mortality by 2330%. Vitamin A supplemen-
tation, given in large doses two or three times per year, is
therefore recommended by the WHO. Given the considerable
effect of vitamin A on mortality, the adequacy of dosing only
a couple of times per year, often in combination with national
immunization days, and the low price per capsule, makes
vitamin A supplementation one of the most cost-effective
health interventions.
Zinc supplementation may prevent diarrhea and pneu-
monia in populations with an inadequate zinc intake and
has also been shown to reduce the duration and severity of
diarrhea when given therapeutically. In contrast to vitamin A,
zinc has to be taken frequently, if not daily, since there are
no body stores. Thus, zinc supplementation may be feasible
in the treatment of children hospitalized or attending health
facilities due to diarrhea but is not a feasible intervention in
the prevention of diarrhea and pneumonia as it would have
to be given daily.
Nutrition, Food Security, and HIV Infection
The synergistic relationship between nutrition and infections is
a central component of the HIV epidemic. The risks and conse-
quences of HIV infection are closely linked through both bio-
logical and social pathways, which are elaborated below.
Nutrition Affects HIV Progression and Transmission
In HIV-infected individuals, micronutrient deciencies and iron
accumulation may accelerate progression of HIV infection, as
shown in the conceptual framework in Figure 2. Deciencies
of antioxidant vitamins and minerals and accumulation of the
prooxidant iron could lead to oxidative stress, which is known
to activate a transcription factor that increases replication of
HIV, which results in increased HIV progression. The iron
accumulation may also result in are-up of latent tuberculosis
(TB) and possibly other infections, which stimulate HIV
replication. Deciencies of micronutrients essential to
immune functions lead to NAIDS, which could contribute to
the risk of coinfections and to the decline in the number of
CD4 cells, that is, the cells infected and destroyed by HIV.
Data from laboratory and clinical studies support this
conceptual framework. Although it is possible that iron
supplementation is harmful, as it may increase HIV
progression, a recent trial providing patients starting
antiretroviral therapy (ART) with iron (one recommended
dietary allowance (RDA)) as part of a multiple micronutrient
fortied food showed no adverse effects (Filteau et al., 2015).
Iron supplementation is given routinely to pregnant women
seeking antenatal care, and occasionally to TB patients
presenting with anemia, even in settings where HIV infection
is prevalent.
Viral load
Oxidative
stress
Iron accumulation
HIV+ Infections HIV+++
MN deficiencies
NAIDS
CD4
Figure 2 Conceptual framework of the role of micronutrient (MN)
deciencies and iron loading in human immunodeciency virus (HIV)
infection. Even early HIV infection (HIV) leads to MN deciencies,
which cause oxidative stress and nutritionally acquired immunode-
ciency syndrome (NAIDS). Oxidative stress and NAIDS may increase
progression of HIV infection (HIV). Modied from Friis, H., 2006.
Micronutrient interventions and HIV infection: a review of current
evidence. Trop. Med. Int. Health 11 (12), 18491857, Blackwell
Publishers.

In contrast, data from randomized, placebo-controlled
trials document a benecial effect of supplementation with
other micronutrients during HIV infection. For example,
among HIV-infected pregnant women in Tanzania not
receiving ART, a daily supplement containing high doses of
vitamins B, C, and E was shown to increase CD4 count and
to reduce HIV load. After 2 years, those receiving the
multivitamins had 29% lower risk of progression to or
dying from AIDS (Fawzi et al., 2004). Similarly, a trial
among adult Thai men and women with HIV infection
found that a daily supplement containing approximately
one RDA of a range of micronutrients reduced mortality
(Jiamton et al., 2003).
Treatment of a HIV or TB does not eliminate the need for
nutritional support, as it is often assumed. In fact, if the infec-
tion has resulted in a growth or weight decit, then treatment,
by allowing a growth spurt or weight gain, considerably
increases nutritional requirements. If these requirements are
not met, then it is likely that the weight gain will result in
fat rather than lean body mass. It is also likely that it may exac-
erbate NAIDS and potentially worsen the outcome of the TB
infection or HIV. Thus, nutritional support providing multi-
ples of the RDA may be needed to meet the requirements
during the initial phase of medical treatment. A trial of
lipid-based nutritional supplement (LNS) fortied with vita-
mins and minerals at three RDA for about 9 weeks around
the start of ART found the vitamins and minerals increased
CD4 count and improved some anthropometric measures
(Filteau et al., 2015). Another randomized trial among HIV
patients initiating ART in Ethiopia found that 3 months
supplementation with LNS resulted in greater gains of lean
body mass, grip strength, and immune recovery, compared
to those starting ART without supplementation (Olsen et al.,
2014). Currently, nutritional assessment, advice, and support
are rarely integrated in the management of HIV infection and
TB in low-income countries.
To the extent nutritional deciency contributes to progres-
sion of HIV and increase in HIV viral load, then it is also likely
to be a determinant of infectiousness and, hence, of mother-to-
child or sexual transmission. As such, the supplement contain-
ing vitamins B, C, and E, mentioned previously, was also found
to reduce mother-to-child HIV transmission (MTCT), although
only among women with signs of poor health. Vitamin A is
essential to a range of immune functions, and initial observa-
tional data suggested that vitamin A supplementation might
reduce MTCT. However, later data from randomized,
controlled trials found no effect of vitamin A supplementation
in two trials and increased transmission in a third (Fawzi et al.,
2002). The vitamin A supplement contained both preformed
vitamin A and provitamin A carotenoids, and it is not clear
which of these compounds caused the increase in transmission,
and why it was not the case in one of the other trials using
a similar intervention (Friis, 2006).
Due to the importance of various nutrients to epithelial
integrity and mucosal immunity, it is likely that deciencies
may also affect susceptibility to infection, when exposed to
HIV. However, there are currently no data to conrm this. On
the other hand, individuals living with food insecurity may
be more prone to engage in risk behaviors which increase their
exposure to HIV.
Nutrition and HIV 273
HIV Infection Impairs Nutritional Status
HIV has direct effects on nutritional status, in addition to the
indirect effects through its impact on food security. HIV infec-
tion increases nutritional requirements by reducing absorption
and increasing utilization and loss of nutrients, and by
increasing resting energy expenditure. Yet, the intake of nutri-
ents and energy may be reduced, due to loss of appetite and
compromised food security.
It has been shown that HIV leads to a decline in muscle
function and thereby reduced work capacity. In sub-Saharan
Africa, many HIV patients are relying on labor-demanding
jobs in the informal sector with no job security or compensa-
tion for lost income if too ill to work. Maintaining physical
capacity and an adequate activity level is thus of crucial impor-
tance for their livelihoods. In addition to the physiological
impact of HIV, the infection is often accompanied by social
stigma, which may further compromise the food security of
patients, by reducing their chances of nding and retaining
work.
HIV affects the whole household when they, in addition to
losing a breadwinner, may have to stay home to look after
a sick family member and face expenses for medical treatment
and transportation. Stigma may also lead to social exclusion,
where HIV-affected households are cut off from their usual
coping strategies, such as borrowing money or food from
others in times of shortfall.
The entire community may become affected by HIV, if
many of its productive members are lost, which may in turn
lead to a decreased agricultural yield or otherwise stagnated
development. While individual supplementation may be
needed at critical points, such as initiation of ART, it is essential
to keep in mind that long-term strategies are also necessary to
protect the livelihoods and food security of people living with
HIV. There is evidence from Uganda that starting ART improves
food security of patients previously food insecure, likely by
improving their physical health so they can go back to work
(Weiser et al., 2012).
Depending on a patients dietary intake of nutrients and
energy, micronutrient status may be impaired, with fat and
particularly lean body mass lost even at early stages of the infec-
tion. With more advanced HIV infection, when opportunistic
and other infections occur, resting energy expenditure is further
increased, whereas food intake may be further reduced, due to
painful sores and infections in the mouth and esophagus. If the
additional energy requirements are not met, then weight will
be lost, unless physical activity is substantially reduced. If the
additional nutrient requirements are not met, then specic de-
ciencies will eventually occur, or existing deciencies will
become exacerbated, which will impair important body func-
tions, including maintenance of lean body mass and immune
functions. An exception is iron. Although absorption of iron
may be impaired, even early HIV infection results in anemia
of infection, which is due to suppression of the production of
red blood cells in the bone marrow. But red blood cells will
continue to age, and eventually be engulfed by white blood
cells and taken to the stores, where iron will accumulate as it
is now longer incorporated into new red blood cells.
Energy requirements are estimated to be 10% higher during
asymptomatic HIV infection to maintain body weight and
274 Nutrition and HIV
Figure 3 Time to death stratied by body mass index (BMI) among patients at antiretroviral therapy (ART) initiation (n 40 778). Modied after
Koethe, J.R., Lukusa, A., Giganti, M.J., et al., 2010. Association between weight gain and clinical outcomes among malnourished adults initiating
antiretroviral therapy in Lusaka, Zambia. J. Acquir. Immune Dec. Syndr. 53 (4), 507513.
physical activity, and they are estimated to be 30% higher
during symptomatic HIV infection (WHO, 2004). In contrast,
protein requirements do not seem to be increased. The require-
ments for most vitamins and minerals are increased, and it is
recommended that patients with HIV eat a healthy diet. In prac-
tice, many patients are advised to take a daily supplement con-
taining one RDA of the essential vitamins and minerals, except
iron. But the extent to which the requirements are increased by
HIV infection is still not clear, as it will be different for different
micronutrients and depend on the stage of HIV infection.
Nevertheless, recommendations should not only be based on
which intakes are necessary to avoid deciency, but also on
which intakes give optimal health, and prevent progression
of HIV infection.
Nutrition and Antiretroviral Treatment
The development of ART and prophylaxis for opportunistic
infections in the mid-1990s was expected to mark the end of
HIV-related weight loss. However, it has been observed that
treatment does not necessarily lead to weight recovery, even
in patients with good viral control, and weight loss continues
to be a common complication of HIV after the global scale-
up of ART.
According to current treatment guidelines, an HIV-infected
individual is only eligible for ART when CD4 counts are
below 500 cells per milliliter, but many do not come for
treatment before the CD4 count is much lower. Since poor
nutritional status is widespread, even in uninfected
individuals, and deteriorates with progression of HIV
infection, it is obvious that many HIV-infected individuals
are in a poor nutritional status at the start of treatment. Data
from large ART programs in sub-Saharan Africa indicate that
one in three patients entering ART care have a body mass
index (BMI, kg m2) below 18.5, indicating some grade of
malnutrition, and one in ten have a BMI below 16,
indicating severe malnutrition. It is likely that nutritional
deciencies will affect absorption and metabolization of one
or more of the different drugs given and hence affect either
efcacy or toxicity of the drugs. Furthermore, unsustainable
access to adequate food is known to be a barrier for
adherence to medical treatment. Indeed, low BMI has
consistently been identied as an independent predictor of
morbidity and mortality during the early phase of ART
(Gupta et al., 2011; May et al., 2010). In a cohort of 40 000
HIV patients initiating ART in Lusaka, Zambia, mild
malnutrition was associated with a twofold risk of death
within the rst 90 days of treatment, while moderate and
severe malnutrition was associated with four- and sixfold
risks, respectively (Koethe et al., 2010; Figure 3). After
90 days of treatment mortality rates became similar between
BMI groups. Other countries have reported similar increases
in mortality risk and show that these persist after controlling
for immune status.
Furthermore, it is known from high-income countries that
some of the ARV drugs affect lipid metabolism and cause mal-
distribution of fat (i.e., lipodystrophia) and metabolic
syndrome with a high risk of coronary heart disease and dia-
betes. It is unknown to what extent prior undernutrition and
inadequate diet during treatment affect the risk of lipodystro-
phia and metabolic syndrome.
Infant Feeding and HIV Infection
For virtually all infants globally, breastfeeding is the safest and
healthiest feeding practice (Figure 4). The WHO recommends
that infants are exclusively breast-fed, that is, given breast
milk and nothing else, for the rst 6 months of life. Infants
should then continue breastfeeding, while also receiving
complementary foods, into the second year of life. These
recommendations are based primarily on the greater survival
of infants in low-income countries who are fed this way, but

Figure 4 There have been rapid changes in international recommen-
dations for human immunodeciency virus (HIV)infected mothers.
Current recommendations are that they follow usual breastfeeding
recommendations for all mothers but also take antiretroviral therapy
(ART). Photo: Henrik Friis.
there is also evidence from high-income countries of improved
health and development of breastfed, compared with non-
breastfed, infants.
The HIV epidemic has called into question the universal
applicability of the WHO recommendations since there is
strong evidence that HIV can be transmitted through breast
milk. A randomized controlled trial conducted in Nairobi,
Kenya, showed an excess 16% MTCT to children allocated to
breastfeeding compared to those allocated to free formula.
However, infants who were not breast-fed in this and other
African studies were at greater risk of infections, particularly
diarrhea, and death from other causes than HIV. HIV-infected
mothers thus had the difcult problem of trying to balance
the risk of transmitting HIV through breast milk with the risk
of their non-breastfed infants dying from other infections.
In order to help these HIV-infected women, WHO and other
international agencies have kept actively in touch with
researchers and policy-makers as ongoing research claries
our understanding of risks and benets of different feeding
modes for HIV-exposed infants. This has resulted in rapid,
every few years, changes in international recommendations.
While this was done for the best of reasons to get scientic
evidence quickly into practice in order to save infant lives it
has often been difcult for health staff to keep abreast of
current recommendations and it has resulted in confusion for
both staff and HIV-infected mothers.
Several areas of research have had particular impact on the
changing WHO recommendations. One relates to the observa-
tion, originally in a study in Durban, South Africa, that early
exclusive breastfeeding was associated with a lower risk of
MTCT than was mixed feeding with breast milk plus other
foods. The mechanism for this effect has not been determined
and, since feeding mode was not randomly assigned in this or
similar observational studies, it is possible that the relationship
is not causal and that both a high risk of transmission and an
inability to breast-feed exclusively are secondary to some other
factor, for example, poor maternal health. The Zambian Exclu-
sive Breastfeeding Study tested in a randomized trial whether
Nutrition and HIV 275
abrupt weaning around 5 months, by removing the usual
period of mixed feeding breast milk and complementary foods,
would decrease MTCT. The group which weaned abruptly had
marginally less MTCT but more illness, and there was no differ-
ence in HIV-free survival at age 2 years. Messages which had
already circulated to health staff that exclusive breastfeeding
with abrupt weaning around 6 months was recommended
thus had to be changed (Kuhn et al., 2008).
Other research trials have focused on provision of different
ART regimens to mothers and infants, often including concom-
itant randomization to different infant feeding modes. The
success of ART at reducing MTCT and the increasing availability
of ART in Africa have led to the current WHO HIV and infant
feeding recommendation of usual breastfeeding practices for
all infants exclusive breastfeeding for 6 months followed by
breastfeeding plus complementary feeding into the second
year of life together with ART provision. These clear feeding
recommendations which harmonize with recommendations
for all women should reduce confusion among women and
health-care staff and also decrease stigma associated with not
breastfeeding in areas where breastfeeding is the norm.
Although there have been concerns that breastfeeding may
have adverse effects on the health of the mother, possibly as
a result of the nutritional stress of lactation, in general research
has not borne this out. As for all lactating women, HIV-infected
women should receive appropriate nutritional, medical, and
psychosocial support to enable successful breastfeeding.
Conclusion
Undernutrition and food insecurity play a pivotal role in the
global HIV/AIDS epidemic, affecting both risks of HIV trans-
mission and the subsequent AIDS-related impacts. The
response to the HIV/AIDS epidemic thus needs to be
comprehensive in focusing on broad-based approaches to
prevention, treatment and care, and mitigation, as well as
interventions to improve nutritional status and food security
globally.
See also: Community-Based Nutrition Programmes; HIV/AIDS
and Tuberculosis; HIV Prevention and Treatment in Children
and Adolescents; Infant Malnutrition: Breastfeeding.
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