HIV Infection/AIDS
Progression
CLASSES FOR IGNOU
MPCE 021 – 26022012 ON HIV/AIDS
Outline
• Trends & Prevalence
• Overview of HIV Infection/AIDS
• Application of Highly Active
Antiretroviral Therapy (HAART)
• AIDS Wasting Syndrome
• HIV-Associated Lipodystrophy
• Nutritional Interventions
• Case Study
• Summary
• Discussion
CONCEPTS from IGNOU
STUDY MATERIAL
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WHAT IS THE PURPOSE OF THIS STUDY?
HIV
AIDS
CD4 CELLS <SEE Slide Natural History-17>
ELISA
WESTERN BLOT
PCR
CANDIDASIS
KAPOSI SARCOMA
CRYPTOCOCCAL MENINGITIS
CONCEPTS from IGNOU
STUDY MATERIAL
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NEURO TOXOPLASMASIS
CMV RETINITIS
PENCILLIUM MARNEFFEI
HERPES ZOSTER
DNA
RNA
PNEUNONITIS, OTTITIS, PHARYNGITIS
GENERALISED LYMPHADENOPATHY
OROPHARYNGEAL CANDIDIASIS
CONCEPTS from IGNOU
STUDY MATERIAL
• DISSEMINATED MACULO-PAPULAR
DERMATOSIS
• OPPORTUNISTIC INFECTIONS
• WINDOW PERIOD or
seroconversion
HAART<WHOLE THERAPY, all
inclusive>
HIV/AIDS Worldwide
(statistics of 2005)
• 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
Top HIV/AIDS-Infected
Countries
1. 2. Nigeria 3. Zimbabwe 10. Russian Federation
4. Tanzania 11. China
5. The Congo 12. Brazil
6. Ethiopia 13. Thailand
7. Kenya 8.
Sub-
Saharan
Africa
South Africa Mozambique
9.
United
States
Source: Steinbrook R. The AIDS epidemic in 2004. NEJM. 2004;351:115-117.
AIDS Rates reported in 2002, US
(Spanish/
+Portu.)
Proportion of AIDS Cases, by Race/Ethnicity
AIDS = Acquired
Immune Deficiency
Syndrome must
Acquired - because it's a condition one
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
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. 2004;351:115-117.
The Human Immune Deficiency
Virus
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 body’s 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
Pathophysiology of HIV/AIDS
• DNA (Deoxyribonucleic acid) the genetic material of nearly all
living organisms, which controls heridity and is located in the
cell nucleus. DNA is a nucleic acid composed of two strands
made up of units called nucleotides. The two strands are
wound around each other in to a double helix and linked
together by hydrogen bonds between the base of the
nucleotides. The genetic information of the DNA is contained
in the sequence of bases along with molecule; changes in the
DNA cause mutations. The DNA molecule can make exact
copies of itself by the process of replication, thereby passing
on the genetic information to the daughter cells when the cell
divides.
• RNA (Ribonucleic acid) a nucleic acid occurring in the nucleus
of and cytoplasm of cells, that is concerned with synthesis of
proteins. In some viruses RNA is the genetic material. The
RNA molecule is a single strand made up of units called
nucleotides.
CD4 Count in HIV infection
• T helper cells (Th cells) are a sub-group of lymphocytes, a
type of white blood cell, that play an important role In the
immune system, particularly in the adaptive immune
system.
• 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.
(inverse relation)
• CD4 counts can also be used to predict the risks for
particular conditions such as pneumonia, CMV disease etc.
• Treatment decisions are based on Viral Load & CD4 count.
CD4 Count in HIV infection
• Cytomegalovirus (from the Greek cyto-, "cell", and
-megalo-, "large") is a viral genus of the viral group
known as Herpesviridae or herpesviruses. It is
typically abbreviated as CMV: The species that
infects humans is commonly known as human CMV
(HCMV) or human herpesvirus-5 (HHV-5), and is the
most studied of all cytomegaloviruses.
• Candida is a genus of yeasts. Many species are
harmless commensals or endosymbionts of animal
hosts including humans, but other species, or
harmless species in the wrong location, can cause
disease. Candida albicans can cause infections
(candidiasis or thrush) in humans and other animals,
especially in immunocompromised patients. Many
species are found in gut flora, including C. albicans in
mammalian hosts, whereas others live as
endosymbionts in insect hosts.
Natural History of Untreated
HIV Infection
Pneumocystis pneumonia (PCP)
• Pneumocystis pneumonia (PCP or pneumocystis)
is the most common opportunistic infection in
people with HIV. Without treatment, over 85% of
people with HIV would eventually develop PCP. It
has been the major killer of people with HIV.
However, PCP is now almost entirely
preventable and treatable.
• PCP is caused by a fungus. It used to be called
pneumocystis carinii, but scientists now call it
pneumocystis jiroveci. A healthy immune
system can control the fungus. However, PCP
causes illness in children and in adults with a
weakened immune system.
• Bactrim or Septra (TMP/SMX) is the most
effective drug against PCP.
Opportunistic Infections
Giardiasis
Epidemiological, clinical and therapeutic
characteristics of giardiasis in a population
of HIV-infected patients with diarrhoic
syndrome. During the period between
1988 and 1995, 720 HIV-patients with
diarrhoic syndrome were evaluated. Fecal
specimens were submitted to
parasitological examination according to
the Ritchie formalin-ethil acetate
centrifugal sedimentation method and
stained with iodine.
HIV-1-associated lymphoma
• HIV-1-associated lymphoma was first incorporated into
the U.S. Centers for Disease Control and Prevention's
(CDC) case definition of AIDS in 1985.(1,2) Prior to the
use of effective antiretroviral therapy, HIV-1-associated
lymphomas constituted 3 to 4% of all AIDS-defining
illnesses reported to the CDC. Following the advent of
effective prophylactic regimens for common HIV-1-
associated opportunistic infections (eg, Pneumocystis
jiroveci, Toxoplasma gondii, cytomegalovirus) and the
development of antiretroviral monotherapies, the
incidence of HIV-1-associated lymphomas remained
constant at 1.6% per year.(3) In 1992, HIV-1-associated
lymphomas were estimated to comprise 8-27% of
approximately 36,000 newly diagnosed cases of
lymphoma.(4) Without effective antiretroviral therapy,
it is estimated that 5-10% of all HIV-infected individuals
will have lymphoma as either an initial or subsequent
AIDS-defining condition.(5) HIV-1-associated
lymphomas thus represent a significant clinical entity
within the spectrum of HIV-1-associated illnesses
SIGNS & SYMPTOMS OF HIV/AIDS
•Assymptomatic for 8 to 10 years
Like in other cases body produce antibodies in
the event of AIDS virus too
Window period/Silent infection = while few
weeks to few months the Window
period<Dormant, result could be negative
initially> It remain silent for 8-10 years for
manifestation of symptoms, hence Silent
infection.
So with major symptoms, tests to be repeated
for confirmation.
Even when it is positive repeat test is done.
•HIV SIGNS & to AIDS.
may lead SYMPTOMS OF HIV/AIDS
Symptoms are classified Major & Minor
Major signs:
Chronic & recurring diarrhea,
Unexplained low fever > 1 month
Dry cough, Fatigue, Progressive dementia
Progressive weight loss, Respiratory infections
recur
Minor signs:
Oral thrush
Recur. Multi dermatomes, Herpez Zoster, skin
infec.
Severe seborrhea dermatitis
Pneumonia
SIGNS & SYMPTOMS OF HIV/AIDS
Oral thrush, also known as oral candidiasis or Moniliasis is a
yeast fungi infection of the genus Candida that develops on the
mucous membranes of the mouth. It is most commonly caused
by Candida albicans, but may also be caused by Candida
glabrata or Candida tropicalis. Candidosis or Moniliasis refers to
adult oral thrush, while "oral thrush" can refer to both adults
and babies.
Oral thrush causes thick white or cream-colored deposits, most
commonly on the tongue or inner cheeks. The lesions can be
painful and may bleed slightly when they are scraped. The
infected mucosa of the mouth may appear inflamed and red.
Seborrheic dermatitis is a common, inflammatory skin
condition that causes flaky, white to yellowish scales to form
on oily areas such as the scalp or inside the ear. It can occur
with or without reddened skin.
Cradle cap is the term used when seborrheic dermatitis affects
the scalp of infants.
NACO GUIDELINES
•NACO(National AIDS Control Orgn.)
idenfications
AIDS in Children (up to 12 yrs. of age)
Positive tests ELISA > 18 months, Maternal HIV
<18 months. & Presence of at least two major
and two minor signs in the absence of known
causes of immuno-suppression.
Major causes:
A) Loss of weight
B) Chronic diarrhea (intermittant/conti.) > 1
month
C) Prolonged fever
-”-
>1
month
NACO GUIDELINES
• Major signs
• Recurrent common infections (e.g.
pneumonitis, ottitis, pharyngitis etc.)
• Generalised lymphadenopathy
• Oropharyngeal candidiasis
• Persistent cough for more than 1 month
• Disseminated maculo-papular dematosis
• CASE DEFINITION of AIDS in ADULTS (for
persons above 12 years of age)
• Two positve tests for HIV infection by ERS &
• Any of the following:
NACO GUIDELINES
• Otitis is a general term for inflammation or
infection of the ear, in both humans and other
animals.
• Lymphadenopathy is a term meaning "disease
of the lymph nodes."[1] It is, however, almost
synonymously used with "swollen/enlarged lymph
nodes". It could be due to infection, auto-immune
disease, or malignancy.
• Inflammation of a lymph node is called
lymphadenitis.[2] In practice, the distinction
between lymphadenopathy and lymphadenitis is
rarely made. (Inflammation of lymph channels is
called lymphangitis.[3])
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(A) Maculo-papular Rash Definition
Maculopapular Rash is a kind of skin disease that is
characterized by certain areas of the skin turning red.
Small lumps arise over these lumps. Sufferers of this
condition can have both papules and macules on their skin.
The term Maculopapular comes from two words –
“macules” meaning flat, small, non-elevated, discolored
regions on the skin and “papules” meaning small, swollen
bumps.
Maculopapular rashes are also referred to as
HIV rashes in medical world.
(B) Pharyngitis, yet another reccurring
complication of HIV
NACO GUIDELINES
• Major signs
• Significant weight loss (>10%) within last one
month/Cachexia = reason not known &
Chronic diarrhea (intermit. or conti.) > 1 month dur.
• Tuberculosis: Extensive pulmonary; disseminated,
miliary, extrapulmonary tuberculosis.
• Neurological impairment preventing independent daily
activities, not knownto be due to the conditions
unrelated to HIV infection (e.g. trauma)
• Candidasis of the oesophagus (diagnosable by oral
candidiasis with odynophagia)
• Clinically diagnosed life-threatening or recurrent
episodes of pneumonia, with or without etiological
confirmation
• Kaposi Sarcoma
• > Cryptococcal menigitis, Neuro Toxoplasmasis, CMV
retinitis, Pencillium marneffei, Recur. H. Zoster or multi
der.
• Disseminated miliary tuberculosis of the skin in
patients with AIDS:
• Generalized tuberculosis with hematogenous dissemination
to multiple organs including the skin. Microscopic
examination of the skin lesions revealed ill-formed or no
granulomata, extensive necrosis, and numerous acid-fast
bacilli. Mycobacterium tuberculosis was detected in the skin
lesions by cultures for three patients and by polymerase
chain reaction for one.
• Odynophagia (from the Greek roots odyno-, pain + -phagia,
from phagein, to eat[1]) is painful swallowing, in the mouth
(oropharynx) or esophagus. It can occur with or without
dysphagia, or difficult swallowing.[2]
• Odynophagia often results in inadvertent weight loss. It can
be caused by many conditions, including very hot or cold
food or drink, drugs, ulcers and mucosal destruction, upper
respiratory tract infections, immune disorders, cancers, and
motor disorders
• Kaposi's sarcoma (KS) is a tumor caused by Human
herpesvirus 8 (HHV8), also known as Kaposi's
sarcoma-associated herpesvirus (KSHV). It was
originally described by Moritz Kaposi (KA-po-she), a
Hungarian dermatologist practicing at the University
of Vienna in 1872.[1] It became more widely known
as one of the AIDS defining illnesses in the 1980s.
The viral cause for this cancer was discovered in
1994. Although KS is now well-established to be
caused by a virus infection, there is widespread lack
of awareness of this even among persons at risk for
KSHV/HHV-8 infection.[2]
• Restated, Kaposi’s sarcoma (KS) is a systemic disease
that can present with cutaneous lesions with or
without internal involvement.
• Cryptococcal meningitis is a fungal infection of the
membranes covering the brain and spinal cord
(meninges).
• Cerebral toxoplasmosis is one of the most common
causes of cerebral mass lesions in
immunocompromised patients. This is true even in the
developing world where tuberculosis is endemic and a
frequent cause of such lesions. [1] Toxoplasmosis is a
parasitic disease caused by the protozoan Toxoplasma
gondii. Toxoplasmic encephalitis usually occurs in
human immunodeficiency virus (HIV)-infected patients
with an absolute CD4 T-cell counts <100 cells/ml [2]
and if diagnosed late and left untreated could lead to
considerable morbidity and mortality.
• Cytomegalovirus (CMV) retinitis is a viral inflammation
of retina of eye.
• Causes, incidence, and risk factors
• CMV retinitis is caused by a member of a group of
herpes-type viruses. CMV is very common. Most people
are exposed to CMV in their lifetime, but typically only
those with weakened immune systems become ill from
CMV infection.
• Penicillium species are usually regarded as
unimportant in terms of causing human disease.
Penicillium marneffei, discovered in 1956, is
different. This is the only known thermally dimorphic
species of Penicillium, and it can cause a lethal
systemic infection (penicilliosis) with fever and
anaemia similar to disseminated cryptococcosis.
• The incidence of P. marneffei is increasing as HIV
spreads throughout Asia. An increase in global travel
and migration means it will be of increased
importance as an infection in AIDS sufferers.
DIAGNOSIS OF HIV/AIDS
• Detects antibody of virus or genetic material
(DNA or RNA of HIV) in blood sample.(+/-)
• Between 2 weeks to 6 months only antibodies
appear in the blood after infection.
• Period between actual infection & detection is
called “WINDOW” period or – Seroconversion.
• Even during this period, one may transmit HIV,
while detection through test is not possible.
• Hence (?) Importance of all safe practices.
TESTS for HIV/AIDS
ELISA: Enzyme-linked immunosorbent assay
Initial test, reliable, if positive done once again. If
negative, usually treated as Negative.
Western Blot: Two positive ELISA demands confirmation,
difficult to perform.
PCR: Polymerase chain reaction (to find RNA of the HIV or
the HIV DNA in while blood cells infected with the virus),
needs expertise to test & expensive. Recent infections
can be detected. Hence safe blood donations.
MISCONCEPTIONS Vs. TRUTH
HIV means y’hv So long as CD4 cells can
AIDS successfully fight, no AIDS
Usual contact Social living will not bring
brings AIDS AIDS. Blood+alleys alone!
If HIV, days are Every ind. Different.
numbered Depends on immune
system. L.E. may be even
100% thru’ med++
HIV exhibit Some may not at all
symptoms
HIV can be cured
Can only be prolonged ++
I am Spared!!
NO. Anyone may get (?)
If -ve Baby’re SURE Need not be. Medicate!!
Manifestations of HIV Infection
Primary Infection Clinical Latency
often asymptomatic or usually asymptomatic
overlooked
Advanced Disease
Symptomatic
Plasma viremia begins to
lymph nodes site of
rise
symptoms 1-6 weeks
ongoing viral latency
CD4 cell count falls
after infection
massive viral production further
destruction of CD4 cells A decline in nutrient
viral like syndrome: sore
status or body
throat, fever,
a decrease in lean body
composition
lymphadenopathy, rash
mass without apparent
Opportunistic infections
total body weight change develop:
differential includes
fever, weight loss,
EBV, CMV, hepatitis,
vitamin B12 deficiency
lymphadenopathy, thrush,
toxoplasmosis
diarrhea, malignancies,
increased susceptibility to wasting syndrome,
antibody (ELISA,
food and water-borne
neurologic syndrome
Western Blot) may not
pathogens.
including dementia
be detected
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,
Kaposi’s Sarcoma, etc. regardless of CD4
cell count
Antiviral Drug Therapy
Nucleoside/
Nucleotide
Analogues
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zalcitabine
Zidovudine
Nonnucleosi
de Reverse
Transcriptas
e Inhibitors
Delavirdine
Efavirenz
Nevirapine
Protease
Inhibitors
Amprenavir
Atazanavir
Fosamprenavir
Indinavir
Lopinavir/Ritona
vir
Nelfinavir
Ritonavir
Saquinavir
Fusion
Inhibitors
Enfuvirtide
How HIV Drugs Work
Adverse Drug Effects
Mitochondrial
dysfunctions
Metabolic
abnormalities
Pancreatitis Lipodystrophy
Fat
accumulation
Lipoatrophy
Peripheral Hyperlipidemia/
neuropathy ? Premature CAD
Lactic acidosis
Hepatic toxicity
Hyperglycemia
Insulin
resistance/DM
Bone disorders:
oesteoporosis and
osteopenia
Hematologic Allergic
complications reactions
Bone Hypersensitivity
marrow reactions
suppression
Skin rashes
Medication Side Effects
–
–
–
–
–
–
Anorexia
Sore/dry/painful mouth
Swallowing difficulties
Constipation/Diarrhea
Nausea/Vomiting/Altered Taste
Depression/Tiredness/Lethargy
Pathogenesis of
Malnutrition
in HIV Infection
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
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 (Highly Active Antiretroviral
Therapy (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.
‘The Wasting Syndrome’
• The wasting syndrome is defined as weight
loss >10% 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.
Pathophysiology AIDS
Wasting
Oxidative Stress
Micronutrient Deficiency
Immune Function
Opportunistic
Infection
Intestinal Parasites
Malabsorption/
Dysphagia
HIV
Pro-inflammatory
Cytokines (TNF alpha)
Metabolic Rate
Endocrine Disorder
Skeletal Protein Breakdown
Anorexia
Dietary Intake
Negative Energy
Balance
Fat Loss
Protein Loss
J AIDS 1988
Potential Mechanisms of
AIDS Wasting
1) Increased energy
expenditure
2) Decreased energy
intake
3) Altered metabolism
4) Hormonal Alterations
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 infections—measured 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
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
clinical status)
(depending on
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 Kaposi’s sarcoma can make chewing and
swallowing difficult and painful.
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.
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.
HIV-Associated
Lipodystrophy
Hyperlipidemia Insulin resistance
Fat Fat
accumulation atrophy
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.
Lipodystrophy
• HIV-associated lipodystrophy is a syndrome that occurs in HIV-
infected patients who are being treated with antiretroviral
medications. Although the term HIV-associated lipodystrophy
refers to abnormal central fat accumulation (lipohypertrophy) and
localized loss of fat tissue (lipoatrophy), some patients have only
lipohypertrophy, some have only lipoatrophy, and, less
commonly, a subset of patients exhibits a mixed clinical
presentation.
• Because no uniform morphologic changes occur with HIV
lipodystrophy, lipohypertrophy and lipoatrophy are considered
distinct entities, with different risk factors and metabolic
processes underlying their development. This article addresses
both lipohypertrophy and lipoatrophy, with a focus on the
morphologic changes and underlying pathophysiology of HIV-
associated lipodystrophy.
• Lipodystrophy can be disfiguring cosmetically. Involvement of the
face is most common and carries a social stigma that may reduce
the quality of life of patients with HIV disease and may pose a
barrier to treatment and reduce medical adherence
What does Lipodystrophy
look like?
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
Nutritional Supplements in
HIV Infection to counteract
AIDS Wasting
•MVI
•Glutamine
•Carnitine
•Appetite
Stimulant
•Hormone Therapy
•Resistance
Training
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)
Fawzi et al.
• Study: Randomized controlled trial of multivitamin
supplementation among HIV-infected pregnant women
in Tanzania.
• Subjects: n=1078, 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
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
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. 1996;46:252-256
Glutamine: ↑body BCM in AIDS
patients with Weight Loss
• Double-blind, placebo-controlled trial
• N=26 patients with >5% 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%) P=0.04 for difference between groups.
• The GLN-antioxidant group gained 1.8kg in body cell mass,
whereas the control group gained 0.4kg (P=0.007.)
• 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 1999;15:860-864
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 cow’s), 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.
• Carnitine’s 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
Carnitine cont’d
(Morretti, et al.)
• Small study (n=11), Italy
• Pt’s 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 carnitine’s 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
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,
possiblyGuidelines for HIV Associated Wasting, Mayo Clinic Proceedings, April 2000
Treatment addictive.
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
Testosterone & Testosterone
Analogues deficiency.
• About half of men with advanced HIV have androgen
• May contribute to muscle wasting.
• May be due to effects of undernutrition, chronic illness, or medications
such as Megesterol acetate’s 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
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
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
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
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
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.
Discussion
Question
s?
References
•
•
•
•
•
•
•
•
Semba RD, Tang AM. Micronutrients and the pathogenesis of human
immunodeficiency virus infection. Br J Nutrition 1999;81:181-9.
Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin
supplements and HIV disease progression and mortality. N Engl J Medicine
2004;351:23-32.
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; 15:865-9
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 1995;8:239-46.
Silva M. Skolnik PR, Gorbach Sl, et al. The effect of protease inhibitors on weight and
body composition n HIV-infected patients. AIDS 1998; 12:1645-51.
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; 31:803-5
Tang, Alice M. et al. Weight loss and survival in HIV-Positive Patients in the Era of
Highly Active Antiretroviral Therapy. JAIDS 2002;31:230-236
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. 1999;23:243-252.
References
•
•
•
•
•
•
•
•
•
•
Kotler, Donald P. Nutritional Alterations Associated with HIV infection.
JAIDS 2000;25:81-87
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
1993;57:15-19
Melchior JC, Salmon D, Rigaud D, et al. Resting energy expenditure is
increased in stable, malnourished HIV-infected patients. AM J Clin Nutr
1991;53:437-41
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; 336:70-1.
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 2001;50:430-434.4
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 2002;14:1-40.
Gerrior, Jul. Nutritional Challenges in HIV Infection. Tufts University School
of Medicine Nutrition Infection Unit
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 1999;15:860-864.
Shabert JK, Wilmore DW. Glutamine deficiency as a cause of
human immunodeficiency virus wasting. Med Hypotheses
1996;46:252-256.
Progression
CLASSES FOR IGNOU
MPCE 021 – 26022012 ON HIV/AIDS
Outline
• Trends & Prevalence
• Overview of HIV Infection/AIDS
• Application of Highly Active
Antiretroviral Therapy (HAART)
• AIDS Wasting Syndrome
• HIV-Associated Lipodystrophy
• Nutritional Interventions
• Case Study
• Summary
• Discussion
CONCEPTS from IGNOU
STUDY MATERIAL
•
•
•
•
•
•
•
•
•
•
WHAT IS THE PURPOSE OF THIS STUDY?
HIV
AIDS
CD4 CELLS <SEE Slide Natural History-17>
ELISA
WESTERN BLOT
PCR
CANDIDASIS
KAPOSI SARCOMA
CRYPTOCOCCAL MENINGITIS
CONCEPTS from IGNOU
STUDY MATERIAL
•
•
•
•
•
•
•
•
•
NEURO TOXOPLASMASIS
CMV RETINITIS
PENCILLIUM MARNEFFEI
HERPES ZOSTER
DNA
RNA
PNEUNONITIS, OTTITIS, PHARYNGITIS
GENERALISED LYMPHADENOPATHY
OROPHARYNGEAL CANDIDIASIS
CONCEPTS from IGNOU
STUDY MATERIAL
• DISSEMINATED MACULO-PAPULAR
DERMATOSIS
• OPPORTUNISTIC INFECTIONS
• WINDOW PERIOD or
seroconversion
HAART<WHOLE THERAPY, all
inclusive>
HIV/AIDS Worldwide
(statistics of 2005)
• 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
Top HIV/AIDS-Infected
Countries
1. 2. Nigeria 3. Zimbabwe 10. Russian Federation
4. Tanzania 11. China
5. The Congo 12. Brazil
6. Ethiopia 13. Thailand
7. Kenya 8.
Sub-
Saharan
Africa
South Africa Mozambique
9.
United
States
Source: Steinbrook R. The AIDS epidemic in 2004. NEJM. 2004;351:115-117.
AIDS Rates reported in 2002, US
(Spanish/
+Portu.)
Proportion of AIDS Cases, by Race/Ethnicity
AIDS = Acquired
Immune Deficiency
Syndrome must
Acquired - because it's a condition one
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
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. 2004;351:115-117.
The Human Immune Deficiency
Virus
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 body’s 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
Pathophysiology of HIV/AIDS
• DNA (Deoxyribonucleic acid) the genetic material of nearly all
living organisms, which controls heridity and is located in the
cell nucleus. DNA is a nucleic acid composed of two strands
made up of units called nucleotides. The two strands are
wound around each other in to a double helix and linked
together by hydrogen bonds between the base of the
nucleotides. The genetic information of the DNA is contained
in the sequence of bases along with molecule; changes in the
DNA cause mutations. The DNA molecule can make exact
copies of itself by the process of replication, thereby passing
on the genetic information to the daughter cells when the cell
divides.
• RNA (Ribonucleic acid) a nucleic acid occurring in the nucleus
of and cytoplasm of cells, that is concerned with synthesis of
proteins. In some viruses RNA is the genetic material. The
RNA molecule is a single strand made up of units called
nucleotides.
CD4 Count in HIV infection
• T helper cells (Th cells) are a sub-group of lymphocytes, a
type of white blood cell, that play an important role In the
immune system, particularly in the adaptive immune
system.
• 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.
(inverse relation)
• CD4 counts can also be used to predict the risks for
particular conditions such as pneumonia, CMV disease etc.
• Treatment decisions are based on Viral Load & CD4 count.
CD4 Count in HIV infection
• Cytomegalovirus (from the Greek cyto-, "cell", and
-megalo-, "large") is a viral genus of the viral group
known as Herpesviridae or herpesviruses. It is
typically abbreviated as CMV: The species that
infects humans is commonly known as human CMV
(HCMV) or human herpesvirus-5 (HHV-5), and is the
most studied of all cytomegaloviruses.
• Candida is a genus of yeasts. Many species are
harmless commensals or endosymbionts of animal
hosts including humans, but other species, or
harmless species in the wrong location, can cause
disease. Candida albicans can cause infections
(candidiasis or thrush) in humans and other animals,
especially in immunocompromised patients. Many
species are found in gut flora, including C. albicans in
mammalian hosts, whereas others live as
endosymbionts in insect hosts.
Natural History of Untreated
HIV Infection
Pneumocystis pneumonia (PCP)
• Pneumocystis pneumonia (PCP or pneumocystis)
is the most common opportunistic infection in
people with HIV. Without treatment, over 85% of
people with HIV would eventually develop PCP. It
has been the major killer of people with HIV.
However, PCP is now almost entirely
preventable and treatable.
• PCP is caused by a fungus. It used to be called
pneumocystis carinii, but scientists now call it
pneumocystis jiroveci. A healthy immune
system can control the fungus. However, PCP
causes illness in children and in adults with a
weakened immune system.
• Bactrim or Septra (TMP/SMX) is the most
effective drug against PCP.
Opportunistic Infections
Giardiasis
Epidemiological, clinical and therapeutic
characteristics of giardiasis in a population
of HIV-infected patients with diarrhoic
syndrome. During the period between
1988 and 1995, 720 HIV-patients with
diarrhoic syndrome were evaluated. Fecal
specimens were submitted to
parasitological examination according to
the Ritchie formalin-ethil acetate
centrifugal sedimentation method and
stained with iodine.
HIV-1-associated lymphoma
• HIV-1-associated lymphoma was first incorporated into
the U.S. Centers for Disease Control and Prevention's
(CDC) case definition of AIDS in 1985.(1,2) Prior to the
use of effective antiretroviral therapy, HIV-1-associated
lymphomas constituted 3 to 4% of all AIDS-defining
illnesses reported to the CDC. Following the advent of
effective prophylactic regimens for common HIV-1-
associated opportunistic infections (eg, Pneumocystis
jiroveci, Toxoplasma gondii, cytomegalovirus) and the
development of antiretroviral monotherapies, the
incidence of HIV-1-associated lymphomas remained
constant at 1.6% per year.(3) In 1992, HIV-1-associated
lymphomas were estimated to comprise 8-27% of
approximately 36,000 newly diagnosed cases of
lymphoma.(4) Without effective antiretroviral therapy,
it is estimated that 5-10% of all HIV-infected individuals
will have lymphoma as either an initial or subsequent
AIDS-defining condition.(5) HIV-1-associated
lymphomas thus represent a significant clinical entity
within the spectrum of HIV-1-associated illnesses
SIGNS & SYMPTOMS OF HIV/AIDS
•Assymptomatic for 8 to 10 years
Like in other cases body produce antibodies in
the event of AIDS virus too
Window period/Silent infection = while few
weeks to few months the Window
period<Dormant, result could be negative
initially> It remain silent for 8-10 years for
manifestation of symptoms, hence Silent
infection.
So with major symptoms, tests to be repeated
for confirmation.
Even when it is positive repeat test is done.
•HIV SIGNS & to AIDS.
may lead SYMPTOMS OF HIV/AIDS
Symptoms are classified Major & Minor
Major signs:
Chronic & recurring diarrhea,
Unexplained low fever > 1 month
Dry cough, Fatigue, Progressive dementia
Progressive weight loss, Respiratory infections
recur
Minor signs:
Oral thrush
Recur. Multi dermatomes, Herpez Zoster, skin
infec.
Severe seborrhea dermatitis
Pneumonia
SIGNS & SYMPTOMS OF HIV/AIDS
Oral thrush, also known as oral candidiasis or Moniliasis is a
yeast fungi infection of the genus Candida that develops on the
mucous membranes of the mouth. It is most commonly caused
by Candida albicans, but may also be caused by Candida
glabrata or Candida tropicalis. Candidosis or Moniliasis refers to
adult oral thrush, while "oral thrush" can refer to both adults
and babies.
Oral thrush causes thick white or cream-colored deposits, most
commonly on the tongue or inner cheeks. The lesions can be
painful and may bleed slightly when they are scraped. The
infected mucosa of the mouth may appear inflamed and red.
Seborrheic dermatitis is a common, inflammatory skin
condition that causes flaky, white to yellowish scales to form
on oily areas such as the scalp or inside the ear. It can occur
with or without reddened skin.
Cradle cap is the term used when seborrheic dermatitis affects
the scalp of infants.
NACO GUIDELINES
•NACO(National AIDS Control Orgn.)
idenfications
AIDS in Children (up to 12 yrs. of age)
Positive tests ELISA > 18 months, Maternal HIV
<18 months. & Presence of at least two major
and two minor signs in the absence of known
causes of immuno-suppression.
Major causes:
A) Loss of weight
B) Chronic diarrhea (intermittant/conti.) > 1
month
C) Prolonged fever
-”-
>1
month
NACO GUIDELINES
• Major signs
• Recurrent common infections (e.g.
pneumonitis, ottitis, pharyngitis etc.)
• Generalised lymphadenopathy
• Oropharyngeal candidiasis
• Persistent cough for more than 1 month
• Disseminated maculo-papular dematosis
• CASE DEFINITION of AIDS in ADULTS (for
persons above 12 years of age)
• Two positve tests for HIV infection by ERS &
• Any of the following:
NACO GUIDELINES
• Otitis is a general term for inflammation or
infection of the ear, in both humans and other
animals.
• Lymphadenopathy is a term meaning "disease
of the lymph nodes."[1] It is, however, almost
synonymously used with "swollen/enlarged lymph
nodes". It could be due to infection, auto-immune
disease, or malignancy.
• Inflammation of a lymph node is called
lymphadenitis.[2] In practice, the distinction
between lymphadenopathy and lymphadenitis is
rarely made. (Inflammation of lymph channels is
called lymphangitis.[3])
•
•
•
•
•
(A) Maculo-papular Rash Definition
Maculopapular Rash is a kind of skin disease that is
characterized by certain areas of the skin turning red.
Small lumps arise over these lumps. Sufferers of this
condition can have both papules and macules on their skin.
The term Maculopapular comes from two words –
“macules” meaning flat, small, non-elevated, discolored
regions on the skin and “papules” meaning small, swollen
bumps.
Maculopapular rashes are also referred to as
HIV rashes in medical world.
(B) Pharyngitis, yet another reccurring
complication of HIV
NACO GUIDELINES
• Major signs
• Significant weight loss (>10%) within last one
month/Cachexia = reason not known &
Chronic diarrhea (intermit. or conti.) > 1 month dur.
• Tuberculosis: Extensive pulmonary; disseminated,
miliary, extrapulmonary tuberculosis.
• Neurological impairment preventing independent daily
activities, not knownto be due to the conditions
unrelated to HIV infection (e.g. trauma)
• Candidasis of the oesophagus (diagnosable by oral
candidiasis with odynophagia)
• Clinically diagnosed life-threatening or recurrent
episodes of pneumonia, with or without etiological
confirmation
• Kaposi Sarcoma
• > Cryptococcal menigitis, Neuro Toxoplasmasis, CMV
retinitis, Pencillium marneffei, Recur. H. Zoster or multi
der.
• Disseminated miliary tuberculosis of the skin in
patients with AIDS:
• Generalized tuberculosis with hematogenous dissemination
to multiple organs including the skin. Microscopic
examination of the skin lesions revealed ill-formed or no
granulomata, extensive necrosis, and numerous acid-fast
bacilli. Mycobacterium tuberculosis was detected in the skin
lesions by cultures for three patients and by polymerase
chain reaction for one.
• Odynophagia (from the Greek roots odyno-, pain + -phagia,
from phagein, to eat[1]) is painful swallowing, in the mouth
(oropharynx) or esophagus. It can occur with or without
dysphagia, or difficult swallowing.[2]
• Odynophagia often results in inadvertent weight loss. It can
be caused by many conditions, including very hot or cold
food or drink, drugs, ulcers and mucosal destruction, upper
respiratory tract infections, immune disorders, cancers, and
motor disorders
• Kaposi's sarcoma (KS) is a tumor caused by Human
herpesvirus 8 (HHV8), also known as Kaposi's
sarcoma-associated herpesvirus (KSHV). It was
originally described by Moritz Kaposi (KA-po-she), a
Hungarian dermatologist practicing at the University
of Vienna in 1872.[1] It became more widely known
as one of the AIDS defining illnesses in the 1980s.
The viral cause for this cancer was discovered in
1994. Although KS is now well-established to be
caused by a virus infection, there is widespread lack
of awareness of this even among persons at risk for
KSHV/HHV-8 infection.[2]
• Restated, Kaposi’s sarcoma (KS) is a systemic disease
that can present with cutaneous lesions with or
without internal involvement.
• Cryptococcal meningitis is a fungal infection of the
membranes covering the brain and spinal cord
(meninges).
• Cerebral toxoplasmosis is one of the most common
causes of cerebral mass lesions in
immunocompromised patients. This is true even in the
developing world where tuberculosis is endemic and a
frequent cause of such lesions. [1] Toxoplasmosis is a
parasitic disease caused by the protozoan Toxoplasma
gondii. Toxoplasmic encephalitis usually occurs in
human immunodeficiency virus (HIV)-infected patients
with an absolute CD4 T-cell counts <100 cells/ml [2]
and if diagnosed late and left untreated could lead to
considerable morbidity and mortality.
• Cytomegalovirus (CMV) retinitis is a viral inflammation
of retina of eye.
• Causes, incidence, and risk factors
• CMV retinitis is caused by a member of a group of
herpes-type viruses. CMV is very common. Most people
are exposed to CMV in their lifetime, but typically only
those with weakened immune systems become ill from
CMV infection.
• Penicillium species are usually regarded as
unimportant in terms of causing human disease.
Penicillium marneffei, discovered in 1956, is
different. This is the only known thermally dimorphic
species of Penicillium, and it can cause a lethal
systemic infection (penicilliosis) with fever and
anaemia similar to disseminated cryptococcosis.
• The incidence of P. marneffei is increasing as HIV
spreads throughout Asia. An increase in global travel
and migration means it will be of increased
importance as an infection in AIDS sufferers.
DIAGNOSIS OF HIV/AIDS
• Detects antibody of virus or genetic material
(DNA or RNA of HIV) in blood sample.(+/-)
• Between 2 weeks to 6 months only antibodies
appear in the blood after infection.
• Period between actual infection & detection is
called “WINDOW” period or – Seroconversion.
• Even during this period, one may transmit HIV,
while detection through test is not possible.
• Hence (?) Importance of all safe practices.
TESTS for HIV/AIDS
ELISA: Enzyme-linked immunosorbent assay
Initial test, reliable, if positive done once again. If
negative, usually treated as Negative.
Western Blot: Two positive ELISA demands confirmation,
difficult to perform.
PCR: Polymerase chain reaction (to find RNA of the HIV or
the HIV DNA in while blood cells infected with the virus),
needs expertise to test & expensive. Recent infections
can be detected. Hence safe blood donations.
MISCONCEPTIONS Vs. TRUTH
HIV means y’hv So long as CD4 cells can
AIDS successfully fight, no AIDS
Usual contact Social living will not bring
brings AIDS AIDS. Blood+alleys alone!
If HIV, days are Every ind. Different.
numbered Depends on immune
system. L.E. may be even
100% thru’ med++
HIV exhibit Some may not at all
symptoms
HIV can be cured
Can only be prolonged ++
I am Spared!!
NO. Anyone may get (?)
If -ve Baby’re SURE Need not be. Medicate!!
Manifestations of HIV Infection
Primary Infection Clinical Latency
often asymptomatic or usually asymptomatic
overlooked
Advanced Disease
Symptomatic
Plasma viremia begins to
lymph nodes site of
rise
symptoms 1-6 weeks
ongoing viral latency
CD4 cell count falls
after infection
massive viral production further
destruction of CD4 cells A decline in nutrient
viral like syndrome: sore
status or body
throat, fever,
a decrease in lean body
composition
lymphadenopathy, rash
mass without apparent
Opportunistic infections
total body weight change develop:
differential includes
fever, weight loss,
EBV, CMV, hepatitis,
vitamin B12 deficiency
lymphadenopathy, thrush,
toxoplasmosis
diarrhea, malignancies,
increased susceptibility to wasting syndrome,
antibody (ELISA,
food and water-borne
neurologic syndrome
Western Blot) may not
pathogens.
including dementia
be detected
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,
Kaposi’s Sarcoma, etc. regardless of CD4
cell count
Antiviral Drug Therapy
Nucleoside/
Nucleotide
Analogues
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zalcitabine
Zidovudine
Nonnucleosi
de Reverse
Transcriptas
e Inhibitors
Delavirdine
Efavirenz
Nevirapine
Protease
Inhibitors
Amprenavir
Atazanavir
Fosamprenavir
Indinavir
Lopinavir/Ritona
vir
Nelfinavir
Ritonavir
Saquinavir
Fusion
Inhibitors
Enfuvirtide
How HIV Drugs Work
Adverse Drug Effects
Mitochondrial
dysfunctions
Metabolic
abnormalities
Pancreatitis Lipodystrophy
Fat
accumulation
Lipoatrophy
Peripheral Hyperlipidemia/
neuropathy ? Premature CAD
Lactic acidosis
Hepatic toxicity
Hyperglycemia
Insulin
resistance/DM
Bone disorders:
oesteoporosis and
osteopenia
Hematologic Allergic
complications reactions
Bone Hypersensitivity
marrow reactions
suppression
Skin rashes
Medication Side Effects
–
–
–
–
–
–
Anorexia
Sore/dry/painful mouth
Swallowing difficulties
Constipation/Diarrhea
Nausea/Vomiting/Altered Taste
Depression/Tiredness/Lethargy
Pathogenesis of
Malnutrition
in HIV Infection
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
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 (Highly Active Antiretroviral
Therapy (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.
‘The Wasting Syndrome’
• The wasting syndrome is defined as weight
loss >10% 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.
Pathophysiology AIDS
Wasting
Oxidative Stress
Micronutrient Deficiency
Immune Function
Opportunistic
Infection
Intestinal Parasites
Malabsorption/
Dysphagia
HIV
Pro-inflammatory
Cytokines (TNF alpha)
Metabolic Rate
Endocrine Disorder
Skeletal Protein Breakdown
Anorexia
Dietary Intake
Negative Energy
Balance
Fat Loss
Protein Loss
J AIDS 1988
Potential Mechanisms of
AIDS Wasting
1) Increased energy
expenditure
2) Decreased energy
intake
3) Altered metabolism
4) Hormonal Alterations
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 infections—measured 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
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
clinical status)
(depending on
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 Kaposi’s sarcoma can make chewing and
swallowing difficult and painful.
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.
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.
HIV-Associated
Lipodystrophy
Hyperlipidemia Insulin resistance
Fat Fat
accumulation atrophy
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.
Lipodystrophy
• HIV-associated lipodystrophy is a syndrome that occurs in HIV-
infected patients who are being treated with antiretroviral
medications. Although the term HIV-associated lipodystrophy
refers to abnormal central fat accumulation (lipohypertrophy) and
localized loss of fat tissue (lipoatrophy), some patients have only
lipohypertrophy, some have only lipoatrophy, and, less
commonly, a subset of patients exhibits a mixed clinical
presentation.
• Because no uniform morphologic changes occur with HIV
lipodystrophy, lipohypertrophy and lipoatrophy are considered
distinct entities, with different risk factors and metabolic
processes underlying their development. This article addresses
both lipohypertrophy and lipoatrophy, with a focus on the
morphologic changes and underlying pathophysiology of HIV-
associated lipodystrophy.
• Lipodystrophy can be disfiguring cosmetically. Involvement of the
face is most common and carries a social stigma that may reduce
the quality of life of patients with HIV disease and may pose a
barrier to treatment and reduce medical adherence
What does Lipodystrophy
look like?
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
Nutritional Supplements in
HIV Infection to counteract
AIDS Wasting
•MVI
•Glutamine
•Carnitine
•Appetite
Stimulant
•Hormone Therapy
•Resistance
Training
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)
Fawzi et al.
• Study: Randomized controlled trial of multivitamin
supplementation among HIV-infected pregnant women
in Tanzania.
• Subjects: n=1078, 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
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
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. 1996;46:252-256
Glutamine: ↑body BCM in AIDS
patients with Weight Loss
• Double-blind, placebo-controlled trial
• N=26 patients with >5% 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%) P=0.04 for difference between groups.
• The GLN-antioxidant group gained 1.8kg in body cell mass,
whereas the control group gained 0.4kg (P=0.007.)
• 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 1999;15:860-864
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 cow’s), 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.
• Carnitine’s 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
Carnitine cont’d
(Morretti, et al.)
• Small study (n=11), Italy
• Pt’s 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 carnitine’s 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
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,
possiblyGuidelines for HIV Associated Wasting, Mayo Clinic Proceedings, April 2000
Treatment addictive.
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
Testosterone & Testosterone
Analogues deficiency.
• About half of men with advanced HIV have androgen
• May contribute to muscle wasting.
• May be due to effects of undernutrition, chronic illness, or medications
such as Megesterol acetate’s 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
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
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
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
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
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.
Discussion
Question
s?
References
•
•
•
•
•
•
•
•
Semba RD, Tang AM. Micronutrients and the pathogenesis of human
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Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin
supplements and HIV disease progression and mortality. N Engl J Medicine
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Melchior JC, Niyongabo T, Henzel D, et al. Malnutrition and wasting,
immunodepression, and chronic inflammation as independent predictors of survival in
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Suttmann U, Ockenga J, Selberg O, et al. Incidence and prognostic value of
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Mittendorfer B, Gore D, Herndon D, et al. Accelerated glutamine synthesis in critically
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References
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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
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Strawford, et al. Resistance Exercise and Supraphisilogic Androgen
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controlled trial. Nutrition 1999;15:860-864.
Shabert JK, Wilmore DW. Glutamine deficiency as a cause of
human immunodeficiency virus wasting. Med Hypotheses
1996;46:252-256.
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