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Food and Nu Tri Tion Tech Ni Cal Assistance
Food and Nu Tri Tion Tech Ni Cal Assistance
NUTRITION
TECH NI CAL
ASSISTANCE
Interactions between antiretroviral therapy (ART) and food and nutrition can
technicalnotes
This technical note provides information and guidance about the food and nutri-
tion implications of ART and how to manage the effects of these implications
in resource limited settings. The purpose of the document is to assist program
planners, groups developing guidance on care and support, service providers,
and networks of people living with HIV/AIDS to understand and address ART
interactions with food and nutrition. The information presented here can also
help managers of programs that include ART components to incorporate food
and nutrition counseling and other interventions as needed. While this docu-
ment is not designed for direct use by community-level health workers, it can be
used to support the development of communication materials such as counsel-
ing aids, as well as training materials.
Acknowledgements
Technical input from the following people
contributed to this technical note: Robert
Mwadime, Regional Centre for Quality of
Health Care; Patricia Bonnard, Paige Har-
rigan, Annette Sheckler, FANTA/AED;
Eunyong Chung, USAID; Victor Masbayi,
USAID/REDSO; Ellen Piwoz, Dorcas Lwanga,
Youssef Tawfik, SARA/AED; Marlou Bijlmsa,
University of Zimbabwe; Cade Fields-Gard-
ner, The Cutting Edge; Roy Kennedy, Medical
University of Southern Africa; Vivica Kraak,
The Cutting Edge; Andrew Thorne Lyman,
World Food Program; and Daniel Raiten,
National Institutes of Health.
2 LIST OF ACRONYMS
When HIV infects a cell, the viral RNA This is referred to as combination therapy
converts to viral DNA and is copied into or highly active antiretroviral therapy
the host cell’s DNA by an enzyme called (HAART). Inclusion of two or more drugs
reverse transcriptase. Then the viral DNA in a single pill is referred to as a fixed dose
instructs the cell to make copies of HIV combination (FDC), and inclusion of two
genetic material. The protease enzyme or more pills containing different drugs in
assembles this copied viral genetic mate- the same blister pack is referred to as a co-
4
rial into new viruses, after which they are blister combination (CBC). WHO recom-
released from the cell to infect other cells. mends four first-line HAART regimens for
adults and adolescents in resource limited
The first class of ARV, reverse transcriptase settings.5
inhibitors, operates early in the HIV life cy-
cle to stop viral replication after HIV has in-
fected a cell. Two types of these drugs exist: Table 2: First-Line ARV Regimens
non-nucleoside reverse transcriptase inhib- Recommended by WHO for Resource
itors (NNRTIs) and nucleoside/nucleotide Limited Settings
reverse transcriptase inhibitors (NRTIs),
also called nucleoside analogues. NNRTIs 1. stavudine + lamivudine + nevirapine
bind onto the reverse transcriptase enzyme
and prevent the HIV RNA from converting 2. zidovudine + lamivudine + nevirapine
into DNA, thereby preventing it from being
copied into the cell’s DNA. NRTIs incorpo- 3. stavudine + lamivudine + efavirenz
rate into the viral DNA and prevent it from
4. zidovudine + lamivudine + efavirenz
producing copies of the virus.
The second class of ARV, protease inhibi- Source: WHO. Scaling Up Antiretroviral Therapy in
tors (PIs), operates later in the life cycle of Resource-Limited Settings: Treatment Guidelines for
HIV. These drugs stop the protease enzyme a Public Health Approach. 2003 Revision. Geneva,
December 2003.
from assembling the new HIV material to
be released to infect other cells.
ing enables effective management of these U.S. Food and Drug Agency
In addition to ARVs, PLWHA often take website: www.fda.gov
interactions to maintain nutritional status
other drugs to treat opportunistic infec-
and to improve drug efficacy, tolerance, Fields-Gardner C., C. Thom-
tions, such as tuberculosis, thrush, pneumo- son, and S. Rhodes.
safety, and adherence.
nia, and intestinal infections, which occur A Clinicians Guide to Nutrition
as a result of weakened immune systems. in HIV and AIDS. American
The examples of specific ARVs’ food inter- Dietetic Association, 1997.
PLWHA also take drugs to treat other
actions given here are intended to illustrate
common diseases, such as malaria. While Pronsky, Z., S.A. Meyer, and C.
the different types of drug-food interac- Fields-Gardner. HIV Medica-
this technical note focuses on ARVs, nutri-
tions. When planning management of drug- tions Food Interactions. Second
tion is a critical factor in the safety and effi-
food interactions, it is important to obtain Edition. Birchrunville, PA: 2001.
cacy of many other medications commonly
complete and up-to-date information from
taken by PLWHA. Many of the principles Zeman F. Clinical
drug product information, medical facilities, Nutrition and Dietetics. Second
and processes described below for ARVs
publications, or other sources. Table 3 pro- Edition. New York: Macmillan,
can be used to identify and manage the 1991.
vides information about food implications
food and nutrition interactions of other
of the 13 ARVs included in WHO’s ARV
drugs. 6
guidelines. 7
ARV Interactions with Food and
1) Food can affect medication absorption,
Nutrition
metabolism, distribution, excretion.
ARVs can interact with food and nutri- Certain foods affect the efficacy of certain 5
tion in a variety of ways, resulting in both ARVs by affecting their absorption, me-
7
positive and negative outcomes. Figure 1 tabolism, distribution, or excretion. Food WHO. Scaling Up Antiretrovi-
ral Therapy in Resource-Limited
depicts the four main types of interactions enhances the efficacy of some ARVs and Settings: Treatment Guidelines
that can occur between drugs and food and inhibits the efficacy of others. For example, for a Public Health Approach.
nutrition. Because different ARVs interact a high energy, high fat, high protein meal 2003 Revision. Geneva, De-
with food and nutrition differently, it is criti- decreases absorption of the PI indinavir. 8 A cember 2003.
cal to understand the specific nutritional high fat meal increases the bioavailability of
8
interactions and implications of the par- the NRTI tenofovir. 9 Pronsky, Z., S.A. Meyer,
and C. Fields-Gardner. HIV
Medications Food Interactions.
Second Edition. Birchrunville,
PA: 2001, p. 81.
Figure 1: Interactions between Medications and Food/Nutrition
9
ibid. p. 126.
1) FOOD MEDICATION ABSORPTION,
(Affects) METABOLISM, DISTRIBUTION,
EXCRETION
NNRTI
ARV Class: REVERSE TRANSCRIPTASE INHIBITORS Carr, A., and D. Cooper.
ARV Type: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) “Adverse Effects of Anti-
retroviral Therapy.” The
Lancet. 2000. 356: 1423-30.
Medication Food Avoid Possible Side Effects
Generic Name Recommendations [Nutritional management of side effects is Fellay, J, et al. “Prevalence of
(abbreviation) given in Table 4.] Adverse Events Associated
with Potent Antiretroviral
efavirenz Can be taken without Alcohol. Elevated blood cholesterol levels, el- Treatment: Swiss HIV Cohort
(EFZ) regard to meals, except evated triglyceride levels, rash, dizziness, Study.” The Lancet. 2001. 358:
do not take with a high anorexia, nausea, vomiting, diarrhea, 1322-27.
fat meal. (A high fat dyspepsia, abdominal pain, flatulence. Pronsky, Meyer, Fields-Gard-
meal increases drug ner, op.cit.
absorption.)
nevirapine Can be taken without St. John’s wort. Nausea, vomiting, rash, fever headache,
(NVP) regard to food. skin reactions, fatigue, stomatitis, abdomi-
nal pain, drowsiness, paresthesia. High
hepatotoxicity.
stavudine Can be taken without Limit the Nausea, vomiting, diarrhea, peripheral
(d4T) regard to food. consumption of neuropathy, chills and fever, anorexia,
alcohol. stomatitis, anemia, headaches, rash, bone
marrow suppression, pancreatitis. May
increase the risk of lipodystrophy.
tenofovir Take with a meal. Abdominal pain, headache, fatigue, dizzi-
(TDF) ness.
zidovudine Better to take without Alcohol. Anorexia, anemia, nausea, vomiting, bone
(ZDV/AZT) food, but if it causes marrow suppression, headache, fatigue,
nausea or stomach constipation, dyspepsia, fever, dizziness,
problems, take with a dyspnea, insomnia, muscle pain, rash.
low-fat meal. Do not
take with a high-fat
meal.
ARV Class: PROTEASE INHIBITORS
PI
Medication Food Possible Side Effects
Avoid
Generic Name Recommendations [Nutritional management of side effects
(abbreviation) is given in Table 4.]
Sources: Pronsky, Z., S.A. Meyer, and C. Fields-Gardner, HIV Medications Food Interactions, 2001.
Nerad, J., M. Romeyn, E. Silverman, J. Allen-Reid, D. Dietrich, J. Merchant,V. Pelletier, D. Tinnerello, and M. Fenton,
“General Nutrition Management in Patients Infected with Human Immunodeficiency Virus.” Clinical Infectious
Diseases. 2003:36.
“Optimizing Anti-HIV Medications,” The Cutting Edge, 2001. [www.tceconsult.org]
WHO. Scaling Up Antiretroviral Therapy in Resource-Limited Settings: Treatment Guidelines for a Public Health Approach.
2003 Revision. Geneva, December 2003.
Table 4: Nutritional Management of Common ARV Side Effects
In some cases, the food interactions of ARV • Certain ARVs cause side effects that
combinations are different from those of affect food consumption, and some side
the individual drugs. For example, as men- effects can be managed by specific food
tioned above, taking the PI indinavir with responses.
a high energy, high fat, high protein meal
reduces its absorption; studies have shown Because of this variation, ARV-food
a 77% reduction in absorption of indinavir management must be drug-specific.
when taken with such a meal. But when
indinavir is taken in combination with the
PI ritonavir, then food has no effect on the
absorption of indinavir, and it may be taken
with or without food.18
All of the recommended combination ARV interactions between drugs and food and
regimens have food and nutrition implica- nutrition. The box below gives an example
tions, though the specifics and the severity of dietary recommendations for a combina-
of ARV-food interactions vary among the tion ARV regimen.
different regimens. Management of the
food and nutrition implications of a par- Furthermore, multiple medications taken
ticular regimen requires consideration of at the same time can interact with each
the food and nutrition interactions of each other, which may enhance or inhibit drug
drug in the regimen, as well as any interac- efficacy and may aggravate side effects. For
tions that may be different due to the drug example, didanosine can interact with ant-
combination (such as the indinavir/ritonavir acids containing magnesium or aluminum,
example described previously). The box leading to increased side effects.19 Hence,
below gives an example of dietary recom- it is important to account for all of the dif-
mendations for a combination ARV regi- ferent drugs being taken – ARVs and others
men. – when planning drug and food consump-
tion.
In addition to combinations of ARVs, other
drugs PLWHA take to treat opportunistic The need to consider drug-drug interac-
infections, malaria, and other diseases may tions applies to traditional therapies as well
also have food and nutrition interactions as modern medications. Many PLWHA use
10 that need to be considered when managing traditional therapies to treat opportunistic
Abacavir has been associated with fatal hypersensitivity reactions, so people who develop
a rash, fever, respiratory symptoms or GI problems should stop taking the combination
regimen and be checked for hypersensitivity. Continuation of the regimen with dietary
management of side effects is only recommended if hypersensitivity has been ruled out.
Sources: WHO. Scaling Up Antiretroviral Therapy in Resource-Limited Settings: Treatment Guidelines for a Public Health
Approach. 2003 Revision. Geneva, December 2003.
Nerad, J., M. Romeyn, E. Silverman, J. Allen-Reid, D. Dietrich, J. Merchant,V. Pelletier, D. Tinnerello, and M. Fenton.
“General Nutrition Management in Patients Infected with Human Immunodeficiency Virus.” Clinical Infectious
Diseases. 2003:36.
“Trizivir brand abacavir + zidovudine + lamivudine (ABC + AZT + 3TC).” AIDSmeds.com.
infections, and some traditional therapies and dietary restrictions can be a significant
can interact with certain ARVs. For exam- obstacle to adherence to ARV regimens.
ple, studies have shown that the blood con- Enabling proper management of ARV-food 20
Piscitelli, S.C., A.H.
centration of the PI saquinavir decreases by interactions is a critical component of en- Burstein, N. Welden, K.D.
50% in the presence of a garlic supplement, suring adherence to ARV regimens. Gallicano, and J. Falloon. “The
Effect of Garlic Supplements
which is sometimes taken as a traditional on the Pharmacokinetics of
therapy to boost the immune system.20 Management of Interactions between Saquinavir.” Clinical Infectious
Diseases. 2002. 34: 234-8.
Because many traditional therapies exist ARVs and Food and Nutrition
and the contents are often unknown, it can
Management of interactions between ARVs
be difficult to understand the interactions
and food and nutrition involves developing
between these therapies and drugs.
and communicating information about the
interactions, identifying and implementing
Adherence to Drug Regimens
appropriate food and nutrition responses,
In addition to direct effects on medication and addressing food security constraints.
efficacy, nutrient absorption, and food-re-
lated side effects, food and nutrition inter- 1) Information
actions with ARVs can also affect PLWHA’s Nutritional implications for ARVs cannot
adherence to drug regimens. Non-adher- be generalized. Given the different types
ence to drug regimens involves failure to of drug-food interactions and the variation
follow drug schedules, taking incorrect among ARVs, it is critical to be drug-specific
11
doses, failure to follow other drug direc- when managing ARV-food interactions. The
tions, or stopping consumption of the drug specific food and nutrition requirements of
altogether. Because ART usually involves a the specific drugs people are taking need
lengthy period of treatment and because to be understood, based upon which ap-
side effects are common, the risk of non- propriate responses can be planned. Con-
adherence to ARV regimens is high. fusion between the food interactions of
different medications may lead to reduced
Non-adherence can have serious nega- efficacy of the medication or to aggravation
tive implications at both the individual of side effects.
and collective levels. For an HIV-infected
individual, interrupting ART or taking it in- Because information about drug-food inter-
correctly may lead to a substantial decline actions continues to evolve, it is important
in health, increased frequency of opportu- to remain up-to-date as new ARVs become
nistic infections, and faster progression of available in a particular context or as new
the disease. Non-adherence may also lead information emerges about existing ARVs.
to development of drug-resistant strains of Three critical steps in this process are: 1)
HIV. The spread of drug-resistant strains of identifying sources of current information
HIV to others creates a greater number of about ARV-food interactions; 2) adapting in-
PLWHA who cannot be effectively treated formation into forms easily understood by
for HIV. PLWHA and caregivers; and 3) identifying
existing communication channels and de-
Failure to effectively manage ARV-food veloping new channels as needed to ensure
interactions can result in non-adherence. that this information reaches PLWHA and
For example, side effects that create sig- caregivers.
nificant discomfort or inhibit eating may
lead PLWHA to interrupt or terminate Websites that contain information about
their drug regimens. Even in developed ARV-food interactions are listed at the end
countries, where PLWHA have greater ac- of this document. Other possible sources of
cess to nutritious foods than in developing information include drug product informa-
countries, food and nutrition side effects tion, medical or nutrition journals, Ministry
of Health facilities and services, pharmaceu- munities to help them understand and
tical services, HIV/AIDS or health resource anticipate the implications of ARVs on food
centers, and books and publications. Com- and nutrition, identify options, and manage
munication channels depend on the specific the economic, social and other constraints.
context and programming environment It is critical for providers to follow up with
but may include existing community-based PLWHA, elicit feedback about what has
or home-based counseling opportunities, been effective and feasible, and facilitate
programs and facilities that provide ARV adjustments as needed. Food and nutri-
services, and mass media campaigns. tion needs and drug-food interactions can
vary between individuals, and appropriate
2) Food and Nutrition Responses responses must be designed to address
Based on information about the specific individual experiences. Opportunities for
food and nutrition interactions of the ARVs such support may exist through home-
and other drugs that an individual is taking, based care, programs and facilities that
an appropriate diet should be identified and provide ARVs, health and nutrition counsel-
a drug and meal timetable planned. This ing sessions, health care services, PLWHA
may involve: networks, or other interventions work-
ing with PLWHA and HIV/AIDS-affected
• adjusting the timing of drug and food
households.
consumption to enable specific drugs to be
taken with or without food as required;
12 Some side effects of ARVs are similar to
• increasing or decreasing consumption of symptoms of opportunistic infections, such
certain foods (or supplements) to compen- as diarrhea. Therefore, while nutritional
sate for drug effects on nutrient absorp- management of drug side effects is im-
tion; portant, one must continue to be alert to
recognize symptoms of opportunistic infec-
• changing the pattern or content of meals
tions and to treat these infections appro-
to address drug side effects;
priately. Nutritional management of a given
• avoiding certain foods contraindicated by symptom is generally the same, whether it
a drug; is caused by a medication side effect or by
• other responses as required by the food an opportunistic infection, but additional
and nutrition interactions of the specific treatment will be required if an underlying
drugs the PLWHA is taking and the indi- infection or condition exists.
vidual PLWHA’s needs and reactions.
The special nutritional needs that HIV and
It is necessary to develop and adhere to a opportunistic infections generate, combined
drug and meal plan that meets the food and with the food consumption constraints that
nutrition requirements of the drugs being symptoms create, make proper nutritional
used and that is feasible and sustainable for intake challenging for many PLWHA irre-
the individual PLWHA. Planning options spective of ART, especially in resource lim-
and diets must account for the obstacles ited settings. ARVs can significantly improve
that constrain PLWHA and households the health of those taking them but can also
from adopting recommended practices. create additional food and nutrition needs
Food insecurity, psychosocial issues, stigma, and constraints for PLWHA.
and intra-household decision-making pro-
cesses are factors that can prevent PLWHA 3) Food Security Constraints to
from following appropriate diets and suit- Management of Food-Drug Interactions
able drug and meal timetables. People living with HIV/AIDS in resource lim-
ited settings may often be unable to follow
Service providers, counselors, and home- optimal food and nutrition recommenda-
based care providers can work with tions for ARVs due to lack of access to the
PLWHA, household members, and com- foods required. For example, PLWHA may
Suggested Steps for Service Providers to Support Dietary Management
of Interactions between ARVs and Food and Nutrition
3. Plan a diet and a drug and meal timetable that address the drug-
food interactions and that meet the PLWHA’s overall nutritional needs.
The plan should account for food security and other constraints faced by 13
the household and the PLWHA. Involve the PLWHA and caregiver in
this planning process.
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AIDS Info
www.aidsinfo.nih.gov
AIDSMeds.Com
www.aidsmeds.com Food and Nutrition
Technical Assistance Project
American Medical Association Academy for Educational
www.ama-assn.org Development
1825 Connecticut Ave., NW
Washington, DC 20009-5721
Association of Nutrition Services Agencies (ANSA)
Tel: 202-884-8000
www.aidsnutrition.org Fax: 202-884-8432
E-mail: fanta@aed.org
Clinical Infectious Diseases http://www.fantaproject.org
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