Nutrition: A Co-factor in HIV Infection/AIDS Progression

1
Nutrition A Co-factor in HIV Infection/AIDS
Progression

• Phara Jourdan
• Rosabelle Campos
• March 28, 2005

2
Outline

• Trends Prevalence
• Overview of HIV Infection/AIDS
• Application of HAART
• AIDS Wasting Syndrome
• HIV-Associated Lipodystrophy
• Nutritional Interventions
• Case Study
• Summary
• Discussion

3
HIV/AIDS Worldwide

• 38 million people live with HIV/AIDS worldwide.

• Sub-Saharan Africa is home to 70 of the people
  living with HIV.

• 2.1 million children are infected
• with HIV/AIDS in the world

4
Top HIV/AIDS-Infected Countries

1. South Africa
2. Nigeria
3. Zimbabwe
4. Tanzania
5. The Congo
6. Ethiopia
7. Kenya
8. Mozambique

9. United States 10. Russian Federation 11. Chin
a 12. Brazil 13. Thailand
Sub-Saharan Africa
Source Steinbrook R. The AIDS epidemic in 2004.
NEJM. 2004351115-117.
5
AIDS Rates reported in 2002, US
6
Proportion of AIDS Cases, by Race/Ethnicity
7
AIDS Acquired Immune Deficiency Syndrome

• Acquired - because it's a condition one must
  acquire or get infected with, not something
  transmitted through the genes
• Immune - because it affects the body's immune
  system, the part of the body which usually works
  to fight off germs such as bacteria and viruses
• Deficiency - because it makes the immune system
  deficient
• Syndrome - because someone with AIDS may
  experience a wide range of different diseases and
  opportunistic infections

8
Modes of Transmission

• Unprotected intercourse
• Injection drug use
• Other unsafe injections
• Blood transfusions
• Direct blood contact
• Mother to child

Sources 2004 Report on the global AIDS epidemic.
Geneva Joint United Nations Program on HIV/AIDS,
July 2004. Steinbrook R. The AIDS epidemic in
2004. NEJM. 2004351115-117.
9
The Human Immune Deficiency Virus
10
Pathophysiology of HIV/AIDS

• A retrovirus unknown until early 1980s
• 1.    Cannot replicate outside of living host
  cells
• 2.    Contains only RNA no DNA
• 3.    Destroys the bodys ability to fight
  infections and certain cancers
• 4. Infects CD4 cells the primary target of
  HIV infection
• Patients infected with HIV are at risk for
  illness and death from
• 1.    Opportunistic infections
• 2.    Neoplastic complications

11
CD4 Count in HIV infection

• The CD4 cell , also known as "T4" or "helper T
  cell is responsible for signaling other parts of
  the immune system to respond to an infection.
• Normal counts range from 500 to 1500 cells per
  cubic millimeter of blood
• Initially in HIV infection there is a sharp drop
  in the CD4 count and then the count levels off to
  around 500-600 cells/mm3. 
• CD4 count is a marker of likely disease
  progression. CD4 percentage tends to decline as
  HIV disease progresses.
• CD4 counts can also be used to predict the risks
  for particular conditions such as Pneumocystis
  carinii pneumonia, CMV disease or MAI disease.
• Treatment decisions are often based on Viral Load
  and CD4 count.

12
Natural History of Untreated HIV Infection
13
Opportunistic Infections
14
Manifestations of HIV Infection
Primary Infection Clinical Latency Advanced Disease
often asymptomatic or overlooked symptoms 1-6 weeks after infection viral like syndrome sore throat, fever, lymphadenopathy, rash differential includes EBV, CMV, hepatitis, toxoplasmosis antibody (ELISA, Western Blot) may not be detected usually asymptomatic lymph nodes site of ongoing viral latency massive viral production destruction of CD4 cells a decrease in lean body mass without apparent total body weight change vitamin B12 deficiency increased susceptibility to food and water-borne pathogens. Symptomatic Plasma viremia begins to rise CD4 cell count falls further A decline in nutrient status or body composition Opportunistic infections develop fever, weight loss, lymphadenopathy, thrush, diarrhea, malignancies, wasting syndrome, neurologic syndrome including dementia
15
AIDS Defined

• HIV positive with a CD4 cell count that is or has
  been less than 200 cells/mm3
• HIV positive with a CD4 percent below 14.
• HIV positive and with an AIDS defining illness
  such as PCP, toxoplasmosis, MAC, Kaposis
  Sarcoma, etc. regardless of CD4 cell count

16
Antiviral Drug Therapy
Nucleoside/ Nucleotide Analogues Nonnucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Fusion Inhibitors
Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zalcitabine Zidovudine Delavirdine Efavirenz Nevirapine Amprenavir Atazanavir Fosamprenavir Indinavir Lopinavir/Ritonavir Nelfinavir Ritonavir Saquinavir Enfuvirtide
17
How HIV Drugs Work
18
Adverse Drug Effects
Mitochondrial dysfunction Metabolic abnormalities Hematologic complications Allergic reactions
Lactic acidosis Hepatic toxicity Pancreatitis Peripheral neuropathy Lipodystrophy Fat accumulation Lipoatrophy Hyperlipidemia/ ? Premature CAD Hyperglycemia Insulin resistance/DM Bone disorders oesteoporosis and osteopenia Bone marrow suppression Hypersensitivity reactions Skin rashes
19
Medication Side Effects

• Anorexia
• Sore/dry/painful mouth
• Swallowing difficulties
• Constipation/Diarrhea
• Nausea/Vomiting/Altered Taste
• Depression/Tiredness/Lethargy

20
Pathogenesis of Malnutrition in HIV Infection
21
Malnutrition can...

• Contribute to impaired immune response
• Result in more rapid disease progression
  shortened survival
• Contribute to increased frequency and severity of
  infections
• Result in fatigue, loss of appetite, sense of
  taste and smell, and decreased quality of life
• Decrease tolerance to therapy and lessen
  medication efficacy

22
Weight Loss Independent Predictor of Mortality

• Weight loss and wasting have been predominant
  features of HIV disease progression since the
  beginning of the HIV/AIDS epidemic and have long
  been established as strong predictors of
  morbidity and mortality in patients infected with
  HIV.
• Several studies in the pre-HAART era showed that
  HIV-related wasting was strongly associated with
  more rapid disease progression and increased
  mortality in HIV-infected patients.
• With the advent of HAART and prophylaxis for
  opportunistic infections, many AIDS-defining
  illnesses that were previously frequent are now
  rarely seen in successfully treated patients.
• So the prevalence of HIV-related wasting syndrome
  has greatly diminished however, several studies
  have concluded that patients treated with HAART
  were still at risk for wasting.
• Wanke et al. found that 1/3 of HIV-infected
  patients in the NFHL study who were treated with
  HAART were still at risk for wasting. Thus
  weight loss, regardless of treatment status,
  remains a strong predictor of death.

23
The Wasting Syndrome

• The wasting syndrome is defined as weight loss
  gt10 of baseline body weight with chronic fever,
  weakness, or diarrhea in the absence of other
  related illnesses contributing to the weight
  loss.
• unexplained weight loss believed to be due to
  the HIV virus
• The wasting syndrome is so common in HIV
  infection that it is classified according to the
  Center for Disease Control (CDC 1987) as a
  diagnostic indicator of AIDS.

24
Pathophysiology AIDS Wasting
Oxidative Stress
Micronutrient Deficiency
Intestinal Parasites
Malabsorption/ Dysphagia
OpportunisticInfection
Immune Function
HIV
Dietary Intake
Pro-inflammatory Cytokines (TNF alpha)
Anorexia
Negative Energy Balance
Metabolic Rate
Endocrine Disorder
Fat Loss
Protein Loss
Skeletal Protein Breakdown
J AIDS 1988
25
Potential Mechanisms of AIDS Wasting

• Increased energy expenditure
• Decreased energy intake
• Altered metabolism
• Hormonal Alterations

26
Energy Expenditure

• A review of the literature shows
• Increased REE depending on the stage of
  immunodeficiency (denoted by the CD4 count) and
  the presence of active infectionsmeasured by
  indirect calorimetry.
• Elevated REE in asymptomatic subjects
• A direct relationship between REE and plasma HIV
  viral burden
• Compared with healthy controls, pts with AIDS and
  active infections had a 34 increase in BMR
  stable pts with AIDS were found to have 21
  increase.

Melchior JC, et al, Mulligan et al
27
Calculating Energy Needs

• BWH standard is BMR x AF x SF weight gain (if
  applicable)
• Injury/Stress Factors
• HIV 8-15
• AIDS 20-30
• AIDS with secondary infection 30
• Protein 1.2 1.8g/kg (depending on clinical
  status)

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Nutritional Problems

• Decreased appetite may result from fever, pain,
  fatigue, emotional stress, and altered sensations
  of taste and smell due to medication side
  effects.
• Lactose intolerance is an early effect of HIV on
  the intestinal tract due to the loss of lactase.
  The HIV infection changes the structure of the
  gut wall, resulting in a decreased lactase level.
  Intolerance results in fermentation causing
  abdominal cramping and a bloated feeling.
• Oral Lesions, caused by Candida albicans, herpes,
  or Kaposis sarcoma can make chewing and
  swallowing difficult and painful.

29
Nutrional Problems (cont)

• Diarrhea and malabsorption can result from direct
  HIV infection in the intestine but are more often
  caused by other pathogens such as bacteria,
  Crytosporidium, or herpes simplex that take
  advantage of the depressed immune system.
• Medications can interfere with eating by causing
  GI discomfort, nausea, vomiting, diarrhea, and
  altered taste
• Depression often leads to isolation, apathy,
  neglect of self-care, and diminished appetite
  all which can affect immunocompetence
• Socioeconomic factors play an important role in
  whether the patient can afford adequate and
  nutritious food.

30
Altered Metabolism

• Early studies documented weight loss and protein
  depletion in untreated patients
• The application of HAART has led to a decreased
  incidence of malnutrition
• Syndrome of altered body fat distribution has
  emerged (lipodystrophy) associated with PIs
• Hypertriglyceridemia, hypercholesterolemia, and
  insulin resistance are commonly seen in patients
  treated with HAART therapy.

31
HIV-Associated Lipodystrophy
Hyperlipidemia
Insulin resistance
Fat atrophy
Fat accumulation
32
What Causes Lipodystrophy?

• Syndrome most likely has a multi-factorial
  etiology
• Most patients who have lipodystrophy started
  noticing symptoms while they were on triple-drug
  therapy.
• Lipodystrophy was first reported among patients
  taking combinations of drugs that included a
  protease inhibitor (PI).
• There are also some patients who have experienced
  one or more symptoms of lipodystrophy without
  taking any anti-HIV drugs at all.
• It's still not clear what role these anti-HIV
  drugs play in the development of lipodystrophy.

33
What does Lipodystrophy look like?
34
Hormonal Factors

• Testosterone deficiency Testostereone levels
  have been found to be markedly reduced in some
  HIV-infected patients and a reduction in free
  serum testosterone levels correlates closely with
  loss of BCM.
• Growth hormone resistance or deficiency Many
  HIV-infected patients with hypogonadism or
  malnutrition display functional GH resistance.
• Anabolic/Anti-catabolic agent
• Important in maintaining protein balance and
  muscle mass

35
Nutritional Supplements in HIV Infection to
counteract AIDS Wasting

• MVI
• Glutamine
• Carnitine
• Appetite Stimulant
• Hormone Therapy
• Resistance Training

36
Role of Micronutrients in the Pathogenesis of HIV
infection

• Micronutrients play important roles in
  maintaining immune function and neutralizing the
  reactive oxygen intermediates produced by
  activated macrophages and neutrophils in their
  response to microorganism
• Micronutrient deficiencies are common among HIV
  infected persons.
• Micronutrient deficiency has been associated with
  further immunopression, oxidative stress,
  subsequent acceleration of HIV replication and
  CD4 T-cell depletion. (semba)

37
Fawzi et al.

• Study Randomized controlled trial of
  multivitamin supplementation among HIV-infected
  pregnant women in Tanzania.
• Subjects n1078, 2 yr study
• Method Compared supplementation consisting of
  multivitamins alone, vitamin A alone, or both
  with placebo
• Results Women who were randomly assigned to
  receive multivitamin supplementation were
• less likely to have progression to advance stages
  of HIV disease,
• had better preservation of CD4 T-cell counts and
  lower viral loads
• had lower HIV-related morbidity and mortality
  rates
• Vitamin A appeared to reduce the effect of
  multivitamins and, when given alone, had some
  negative effects
• Conclusion Multivitamin supplementation could
  reduce the risk of or delay HIV-associated
  disease and mortality.

New England Journal Medicine, 2004
38
Glutamine Application in HIV/AIDS

• Glutamine is the most abundant amino acid in the
  body and is considered a conditionally essential
  amino acid during periods of catabolism.
• During periods of increased metabolic stress,
  glutamine is released freely from the skeletal
  muscle, and intracellular glutamine
  concentrations fall by more than 50
• Increased de novo synthesis of glutamine in the
  skeletal muscle often results in muscle-wasting
  syndrome
• Glutamine synthesis cannot keep up with the
  higher requirements during stress.
• Individuals deficient in glutamine manifest
  changes in gut morphology including increased
  membrane permeabilitiy resulting in bacterial
  translocation, malabsorption, and diarrhea
• Lack of support to immunocytes and fibroblasts
  cause immunosuppression and impaired wound
  healing

39
Glutamine Application in HIV/AIDS (cont)

• Data suggest that glutamine supplementation
  offers the potential to limit skeletal muscle
  wasting, reduce diarrhea and malabsorption,
  enhance immune host defense, and reduce the
  incidence of opportunistic infections associated
  with HIV infection and AIDS Shabert J et al. Med
  Hypotheses. 199646252-256

40
Glutamine ?body BCM in AIDS patients with Weight
Loss

• Double-blind, placebo-controlled trial
• N26 patients with gt5 weight loss since disease
  onset
• Subjects received GLN-antioxidants (40g/d) in
  divided doses or glycine (40g/d) as the placebo
  for 12 wks.
• Result Over 3 mos, the GLN-antioxidant group
  gained 2.2kg in body weight (3.2), whereas the
  control group gained 0.3kg (0.4) P0.04 for
  difference between groups.
• The GLN-antioxidant group gained 1.8kg in body
  cell mass, whereas the control group gained 0.4kg
  (P0.007.)
• Intracellular water increased in the
  GLN-antioxidant group but not in the control
  group.
• In conclusion, GLN-antioxidant supplementation
  can increase body weight, body cell mass, and
  intracellular water when compared with placebo
  supplementation.

• Shabert J, Winslow C. et al. Nutrition
  199915860-864

41
L-Carnitine in HIV Infection

• Carnitine is a conditionally essential amino
  acid found predominantly in red meat. It is also
  found in milk (human and cows), pork, lamb,
  tempeh, and supplements.
• It is conditionally essential because the body
  can make it from lysine and methionine with
  assistance from Vitamin C and other compounds
  produced in the body.
• Carnitine is synthesized in the Kidney and stored
  in the muscles.
• Carnitines function is to shuttle long-chain
  fatty acids into the mitochondria to be utilized
  as fuel.
• HIV/AIDS is a risk factor for carnitine
  deficiency

42
Carnitine contd (Morretti, et al.)

• Small study (n11), Italy
• Pts refusing ART, normal Carnitine levels,
  stable weight, declining CD4 counts, asymptomatic
• 6 g intravenous Carnitine Qday times 150 days
• By second week, all subjects report increased
  feeling of well-being
• CD4 cell counts significantly increased by day 90
  and 150, but there was an evident
  (non-significant) positive trend at day 15 and 30
  compared to baseline.
• Overall upward trend in CD8 cell counts as well
• Only moderate changes in plasma viral load
• No toxicity was reported at this level
• Authors conclude that carnitine targets immune
  system rather than virus
• Authors propose possibility that carnitines
  antiapoptotic effect could be due to antioxidant
  activity

Morretti, et al. Effect of L-Carnitine on Human
Immunodeficiency Virus-1 Infection-Associated
Apoptosis A Pilot Study, Blood, Vol 91, No. 10,
May 15, 1998 pp 3817-3824
43
Appetite Stimulant Dronabinol

• Derived from delta-9-tetrahydrocannabinol (major
  active component of Marijuana)
• Useful in decreasing nausea and increasing
  appetite
• Insignificant gains or even loss of total BW
• May induce central nervous system events such as
  anxiety, confusion, emotional lability and
  hallucinations, possibly addictive.

• Treatment Guidelines for HIV Associated Wasting,
  Mayo Clinic Proceedings, April 2000

44
Appetite Stimulant Megestrol Acetate (Megace)

• A synthetic derivative of the natural steroid
  hormone, progesterone.
• Improved appetite in a number of studies
• Takes two weeks for effect.
• Considerable increases in BW, although mostly in
  body fat
• May be due to testosterone lowering effect, not
  reversed by supplementation w/testosterone
• May induce or exacerbate DM, cause adrenal
  insufficiency when abruptly discontinued after
  long-term use

Treatment Guidelines for HIV Associated Wasting,
Mayo Clinic Proceedings, April 2000
45
Testosterone Testosterone Analogues

• About half of men with advanced HIV have androgen
  deficiency.
• May contribute to muscle wasting.
• May be due to effects of undernutrition, chronic
  illness, or medications such as Megesterol
  acetates effect on gonadotropin secretion.
• 25 have primary hypogondadism most often
  idiopathic but may be due to OI, malignant
  infiltration of testes, or testicular effects of
  HIV infection or medication.
• Most studies have shown IM testosterone
  supplementation to result in wt gain, increased
  LBM, overall feeling of well-being.
• Studies of testosterone analogues show varied
  efficacy in improving nutritional status but may
  carry risks for hepatic toxic effects
• Nandrolone decanoate 100mg/mL IM q 2wks
  increased BW, LBM and quality of life.
• Oxymethalone 150 mg/day found to have similar
  results
• Testosterone cypionate 200mg IM q 2wks for 3 mos,
  no result except for increased quality of life.

• Treatment Guidelines for HIV Associated Wasting,
  Mayo Clinic Proceedings, April 2000

46
Growth Hormone

• AIDS pts may be growth hormone resistant. In
  studies of GH in AIDS pts, doses used are
  significantly higher than those required for
  replacement.
• GH has been shown to increase LBM and protein
  synthesis and reduce urinary nitrogen excretion.
• GH costs 18,000/yr but Medicaid has approved
  reimbursement, making this therapy more
  accessible.
• Short-term use of growth hormone (12 wks) has
  effects on wt gain that persist after therapy is
  discontinued.
• Using GH for short periods when required, rather
  than as continuous therapy will minimize costs
  while maximizing patient nutritional status.
• Indicated for use when all other methods have
  failed and pt has normal testosterone levels or
  on replacement testosterone for at least 4-6 wks.
• Contraindicated if pt has malignancy

Treatment Guidelines for HIV Associated Wasting,
Mayo Clinic Proceedings, April 2000
47
Resistance Training

• Supervised exercise training is a promising
  anabolic strategy for pts with AIDS.
• Studies of exercise training have shown increased
  muscle function, wt gain, strength, LBM.
• Effects of resistance training alone in AIDS
  wasting pts remains unknown.
• However, use of resistance training with
  testosterone and oxandralone has been shown to be
  effective in AIDS pts with AIDS wasting.

Journal of the American Medical Association,
April 14 199, Volume 281(14), pp 1282-1290. The
New England Journal of Medicine, June 3 1999
48
Resistance Training (cont)

• Strawford, et al studied 24 eugonadal men with
  HIV associated wt loss. All subjects received
  supervised progressive resistance exercise with
  physiologic IM testosterone replacement 100 mg/wk
  to suppress endogenous testosterone for 8 weeks.
• Randomization was between anabolic steroid,
  oxandralone, 20 mg/day and placebo.
• Measured LBM, nitrogen balance (10d met ward
  measure), body wt, muscle strength, and androgen
  status
• Result 22 completed the study (11per group).
  Both showed sig increase in N retention, LBM, wt,
  and strength. The mean gains were sig greater in
  oxandrolone group than in placebo, greater
  strength gains for upper/lower body muscle groups
  by max wt lifted, and dynomometry. Mean HDL
  cholesterol dropped sig in oxandrolone group.
  Protease inhibitors made no difference in
  outcome.
• Conclusion moderate androgen regimen (with
  oxandrolone) substantially increased lean tissue,
  strength gains from PRE, compared to testosterone
  replacement alone.

Journal of the American Medical Association,
April 14 1999
49
Summary

• HIV/AIDS remains an epidemic worldwide
• Malnutrition is a complication in HIV related
  morbidity and mortality
• Weight loss is an independent predictor of
  mortality
• Despite HAART, patients remain at risk for AIDS
  wasting syndrome
• Contributors of AIDS wasting syndrome include
  increased energy expenditure, decreased energy
  intake, altered metabolism, and hormonal factors
• Multivitamin supplementation could reduce the
  risk of or delay HIV-associated disease and
  mortality.
• Data suggest glutamine supplementation may help
  limit skeletal muscle wasting and increase BCM in
  patients with weight loss

50
Summary (cont)

• Pts have been found to be deficient in Carnitine,
  may benefit from supplementation since it may
  have antiapoptic effect through antioxidant
  activity.
• Appetite Stimulants may result in wt gain, but
  mostly in fat and may also have some negative
  side effects.
• Testosterone deficiency may lead to wasting,
  supplementation may be beneficial leading to
  improved sense of well being, strength, etc,
  however Testosterone analogues may be
  hepatotoxic.
• Correction of Growth Hormone resistance may help
  reverse wasting, but it is a costly intervention
  if pt does not have Medicaid. Short term use has
  been shown to be beneficial.
• Resistance training has been shown to increase wt
  and LBM, but one study found that training plus
  oxandralone was most beneficial.

51
Discussion
Questions?
52
References

• Semba RD, Tang AM. Micronutrients and the
  pathogenesis of human immunodeficiency virus
  infection. Br J Nutrition 199981181-9.
• Fawzi WW, Msamanga GI, Spiegelman D, et al. A
  randomized trial of multivitamin supplements and
  HIV disease progression and mortality. N Engl J
  Medicine 200435123-32.
• Melchior JC, Niyongabo T, Henzel D, et al.
  Malnutrition and wasting, immunodepression, and
  chronic inflammation as independent predictors of
  survival in HIV-infected patients. Nutrition
  1999 15865-9
• Suttmann U, Ockenga J, Selberg O, et al.
  Incidence and prognostic value of malnutrition
  and wasting in human immunodeficiency
  virus-infected outpatients. J Acquir Immune
  Defic Syndrome Hum Retrovirol 19958239-46.
• Silva M. Skolnik PR, Gorbach Sl, et al. The
  effect of protease inhibitors on weight and body
  composition n HIV-infected patients. AIDS 1998
  121645-51.
• Wanke CA, Silva M, Knox TA, et al. Weight loss
  and wasting remain common complications in
  individuals infected with human immunodeficiency
  virus in the era of highly active antiretroviral
  therapy. Clin Infect Dis 2000 31803-5
• Tang, Alice M. et al. Weight loss and survival in
  HIV-Positive Patients in the Era of Highly Active
  Antiretroviral Therapy. JAIDS 200231230-236
• Mittendorfer B, Gore D, Herndon D, et al.
  Accelerated glutamine synthesis in critically ill
  patients cannot maintain normal intramuscular
  free glutamine concentration. J Parenter Enteral
  Nutri. 199923243-252.

53
References

• Kotler, Donald P. Nutritional Alterations
  Associated with HIV infection. JAIDS
  20002581-87
• Ott M, Lambke B, Fischer H, et al. Early changes
  of body composition in human immunodeficiency
  virus-infected patients tetrapolar body
  impedance analysis indicates significant
  malnutrition. Am J Clin Nutr 19935715-19
• Melchior JC, Salmon D, Rigaud D, et al. Resting
  energy expenditure is increased in stable,
  malnourished HIV-infected patients. AM J Clin
  Nutr 199153437-41
• Rivera S, Briggs W, Qian D, et al. HIV RNA
  levels correlate with prior weight loss.
• Mulligan k, Tai VW, Schambelan M. Energy
  expenditure in human immunodeficiency virus
  infection. N engl J Med 1997 33670-1.
• HIV Prevalence in the United States, 2000. 9th
  Conference on Retroviruses and Opportunistic
  Infections, Seattle, Wash., Feb. 24-28, 2002.
  Abstract 11.
• Centers for Disease Control and Prevention (CDC).
  HIV and AIDS - United States, 1981-2001. MMWR
  200150430-434.4
• Centers for Disease Control and Prevention (CDC).
  HIV Prevention Strategic Plan Through 2005.
  January 2001.5.
• Centers for Disease Control and Prevention (CDC).
  HIV/AIDS Surveillance Report 2002141-40.
• Gerrior, Jul. Nutritional Challenges in HIV
  Infection. Tufts University School of Medicine
  Nutrition Infection Unit

54
References

• Morretti, et al. Effect of L-Carnitine on Human
  Immunodeficiency Virus-1 Infection-Associated
  Apoptosis A Pilot Study, Blood, Vol 91, No. 10,
  May 15, 1998 pp 3817-3824
• Treatment Guidelines for HIV Associated Wasting,
  Mayo Clinic Proceedings, April 2000, Volume
  75(4), pp 386-394.
• Drug Therapy Treatments for Wasting in Patients
  with the Acquired Immunodefeciency Syndrome, The
  New England Journal of Medicine, June 3 1999,
  Volume 340(22), pp 1740-50.
• Strawford, et al. Resistance Exercise and
  Supraphisilogic Androgen Thearpy in Eugonadal Men
  with HIV-Related Weight Loss A Randomized
  Controlled Trial, Journal of the American Medical
  Association, April 14 1999, Volume 281(14), pp
  1282-1290.
• Shabert J, Winslow C, Lacey JM. Wilmore DW.
  Glutamine-antioxidant supplementation increases
  body cell mass in AIDS patients with weight loss
  a randomized, double-blind controlled trial.
  Nutrition 199915860-864.
• Shabert JK, Wilmore DW. Glutamine deficiency as a
  cause of human immunodeficiency virus wasting.
  Med Hypotheses 199646252-256.