Transcript HIV Disease

HIV Disease
Transmission Variables
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How easily a virus can enter the body
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Encounter rates
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Influenza and SARS enter by respiratory tract
Easy to infect
HIV is hard to enter the body. Usually needs sexual contact
The number of opportunities that an uninfected person has with
an infected person
More contacts, the higher the probability of becoming infected.
Population density
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Large populations allow epidemics to occur.
Many people die, but some people able to survive pass on their
genetics
Over time the virus becomes stable in the population but few
people die due to immunity
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Sickle Cell Anemia – Good for Malaria.
More Variables
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Percent of people with the disease in a population or
subpopulation.
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Duration of lifespan before death
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Population may be bar members, racial groups, select minority
group (MSMs) region of the country, nation, etc.
More people with HIV, the higher the risk of getting HIV if you
have sex with someone.
Rapid death, fewer people to pass on the virus
Ebola
Geographic Isolation
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If isolated, fewer people can become exposed
Difficult with global transportation SARS
Risk Behaviors
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ANY BEHAVIOR THAT RESULTS IN THE
TRANSMISSION OF BODY FLUIDS PLACES
A PERSON AT HIGH RISK FOR BBPS
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HIV
Hepatitis
STD’s
ROUTES OF TRANSMISSION
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Sexual transmission
Blood contact during needle sharing
Perinatally
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Blood Transfusions
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Mother to baby before or during delivery
Rare in US today
Higher in third world
Other
Risk Behaviors
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Anal intercourse with internal ejaculation without a condom
Vaginal intercourse with internal ejaculation without a condom or barrier
Vaginal intercourse with internal ejaculation without a condom but with spermicidal foam
Anal intercourse with a condom and withdrawing prior to ejaculation
Vaginal intercourse without spermicidal foam or condom and withdrawing prior to ejaculation
Vaginal intercourse using spermicidal foam but without a condom and withdrawing prior to
ejaculation
Sharing sex toys by more than one partner without a condom
Anal Fisting
Fisting
Anal intercourse with internal ejaculation with a condom and spermicide
Vaginal intercourse with internal ejaculation with a condom and no spermicide
Vaginal intercourse with internal ejaculation with a condom and spermicide
Anal intercourse with a condom, spermicide, and withdrawing prior to ejaculation
Vaginal intercourse with a condom, spermicide, and withdrawing prior to ejaculation
Fellatio without a condom and ejaculation in the mouth
Fellatio without a condom, placing the penis in the mouth, and withdrawing prior to ejaculation
Fellatio to orgasm with a condom
Fellatio without a condom but not putting the head of the penis inside of the mouth
Cunnilingus
Use of sex toys with condoms or not shared
Mutual masturbation with orgasm on, but not in the partner
Intercourse between the thighs
Frottage (rubbing a person for sexual pleasure)
Mutual masturbation with internal touching using finger cots or condoms
Mutual masturbation with only external touching
Deep wet kissing
Masturbation with another person but not touching one another
Hugging/massage/dry kissing
Masturbation alone
Abstinence
Shernoff, 1988
Course of HIV Disease
Overview
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Is a slow virus
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Mutates rapidly
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Uses the bodies DNA to hide
Uses other processes
Does not kill the host for a long period
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Allows the virus to pass on its genetic codes to many
people.
Not like Ebola which kills the host in a couple of
weeks
Result – From a virus standpoint, is an ideal
virus
HIV Infection Occurs
Acute Retroviral Syndrome Occurs
Antibodies Develop
Asymptomatic
Symptomatic HIV Disease
AIDS
Death
Initial Infection
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Risk depends on the type of activity
If know the person was positive, may be able to
stop the virus from replicating enough so the
immune system can destroy it.
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Use full battery of HIV drug cocktails
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Will not be used for general risk populations
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IDU’s
MSM’s
May be used for medical exposure or other reasons
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See MMWR
Needle stick
Rape
Drug cocktails do not work for other STDs or Hepatitis
Acute Retroviral Syndrome
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Usually occurs in 2-4 weeks
May occur up to 12 weeks
Symptoms
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Fever, body aches, sore throat, headache malaise
Diarrhea, swollen lymph nodes, others
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May feel like a case of the flu.
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Treat symptomatically
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ASA, bed rest, etc.
Symptoms usually last 1-2 weeks then go away
Inside the Body
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Virus is being widely disseminated
High levels of the virus initially occurred
then drop off.
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Antibody production begins
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No immune response yet to combat it
Destroys lots of the virus but not all
Virus infects Thelper Lymphocytes
Virus continues to replicate in lymph tissue
Antibody Development
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Begins about 2-3 weeks
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Can be detected in about 12 days with specialized
testing which is expensive
Usually detectable within 3 months
If exposed, 99.9% of the people will be
detectable with 6 months
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Several tests
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Viral culturing
PCR Polymerase Chain Reaction
Reverse Transcriptase
Others
Asymptomatic Stage
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Median time 10 years in most people
Virus proliferates in lymphatic system
Virus also continues to replicate and
destroy immune system cells
Initially does not cause life-threatening
diseases
May experience a variety of symptoms
during this period
Symptoms can be brief or chronic
Some Symptoms
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Recurrent swollen lymph glands
Diarrhea
Fever
Weight loss
Oral and Vaginal Yeast infections
Others
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Symptoms can also result from other diseases
Bacteria
Fungus
Parasites
Behaviors
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Person may not know they have HIV
Person may suspect they have HIV but will
not get tested so they can say, “I do not
know if I have the disease.”
Sexual activity may continue, increase, or
decrease
Chronic Symptomatic HIV Disease
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Immune system is being further deteriorated
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Symptoms become more frequent
Symptoms last longer
Ultimately overwhelms lymphatic system
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T4 or CD4+ cells decrease
Large increase of virus in the bloodstream
Seems to be a marker against stopping the disease
30% of people who do not take medications
develop AIDS-Related infections in 5 years.
AIDS
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Diagnosed when the following occurs
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CD4 + T lymphocyte counts <200
cells/microliter
CD4 + T lymphocyte count <14% of total
lymphocytes
Experiences opportunistic infections
Generally, the immune system is unable to
control HIV replication.
Some Opportunistic Infections
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Pneumocystis Carinii Pneumonia
Kaposi’s sarcoma
Recurrent Pneumonia
Candidiasis
Toxoplasmosis of the Brain
Many Other Disorders as Well
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Wasting Syndrome
Candidiasis of bronchi, trachea, lungs,
esophagus
Cytomegalovirus
Encephalopathy
Histoplasmosis
Lymphoma’s
Many others
With Aids
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Immune system continues to deteriorate
Other diseases occur (TB)
Drugs may prolong lifespan
Degree of impairment varies from day to
day and week to week.
Person experiences many personal and
societal issues
Physical Issues
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Persons become debilitated by symptoms
Commonplace behaviors become difficult
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Hard to have steady employment
May have difficulty shopping for food
Hard to do chores at home
Psychological/Neurological Issues
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Progressive dementia occurs in 55%-65%
of cases
Some estimates - 90% have dementia
Pathological CNS changes found in 80% of
HIV cases
AIDS-Related Dementia
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Solely associated with AIDS
Early symptoms
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Forgetfulness
Recent memory loss
Loss of concentration
Loss of thought
Movement problems - balance
Late Symptoms
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Loss of speech
Fatigue
Bladder and bowel incontinence
Seizures
Coma
Death
Some Neurological Problems
Associated with HIV Infection
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Asymptomatic infection – no mental
impairment
AIDS Dementia Complex (ADC)
Acute Encephalitis
Aseptic Meningitis
Distal sensory neuropathy
Treatment
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PREVENTION IS THE BEST TREATMENT
After becoming infected
Keep the immune system from becoming taxed
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Your genetics is important
Good nutrition
Exercise
Counseling if necessary
Peer support network
Social Services Support
Drugs
Drugs
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Are designed to target virus replication at
different points
HIV VIRUS
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Reverse Transcriptase
ssRNA
CD4 Receptor
Reverse Transcriptase
HIV
VIUS
CXCKR-4
(fusin)
CC-CKR-5
ss DNA
Genome
RNA
ds DNA
RT
Viral RNA
Mature
HIV
MRNA
Protease
HIV Bud
Viral Proteins
CD4 Receptor
VIRUS
ss DNA
ds DNA
Genome
RNA
RT
1
Viral RNA
Mature
HIV
MRNA
Add
Protease
2
Viral Proteins
HIV Bud
Reverse Transcriptase Inhibitors
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Two groups
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Nucleoside Analogs
Non-Nucleoside Analogs
Generally are designed to interfere with the
viruses ability to replicate itself
Nucleoside Analogs’
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Called Nukes
Interferes with the virus’s ability to
replicate itself
Stops the synthesis of the DNA strand
Incorporate into the elongating strand of
viral DNA
Generally stops RT replication of HIV-DNA
Names by Year of Introduction
Zidovudine
ZDV/Retrovir
1987
AZT
Retrovir
1987
Didanosine
ddI, Videx
1991
Zalcitabine
ddC, Hivid
1994
Stavudine
d4T, Zerit
1994
Lamivudine
3TC, Epivir
1995
Abacavir
Ziagen
1998
Non Nucleoside Compounds
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Called non-Nukes
Are not structurally or chemically similar to
nucleosides
Are often used in triple-therapy regimes
Prevent the conversion of HIV RNA into HIV DNA
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Unlike Nucleoside compounds do not incorporate into
the DNA
Instead, binds directly to the RT
Names by Year
Nevirapine
Viramune
1996
Delavirdine
Rescriptor
1997
Efavirenz
Sustiva
1998
Others
Under
Development
Problem
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Initially worked
HIV resistant strains developed in weeks
Better results when used in combination
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Did not increase survival rates
Do extend the asymptomatic period
Allows you to delay the onset of Protease
Inhibitors
May interfere with oral contraceptives
Examples of Side effects
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Liver Toxicity
Rash
Nevirapine (Viramune)
Other Problems
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15% of HIV infected people cannot
tolerate nucleoside or non-nucleoside
compounds.
Both groups are time limited for
effectiveness.
Protease Inhibitors
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Newest line of defense
HIV protease generally cuts viral strands
Is essential for viral replication
PI basically stop the virus from maturing
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Blocks the binding and cutting sites for viral
protease
Result- Virus not cut – cannot replicate
Also indirectly decrease the production of RT
Names by Year
Saquinavir
Mesylate
Ritonavir
Indinavir
Nelfinavir
Saquinavir
Amprenavir
ABT-378
Others
Invirase
1995
Norvir
Crixivan
Viracept
Fortovase
Agenerase
Kaletra
Under
1996
1996
1997
1997
1999
2000
Testing
Protease Cutting Sites
Protease Cutting Proteins
Result
Different Lengths of Protein that
Perform Different Tasks
Protease Inhibitors Prevent Protease from
Entering Cleavage Sites
Result, No Cleavage
HIV Remains Immature and Cannot Replicate
Drug Resistance
Drug-Resistant Nucleoside
Analog Mutations
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RT is unable to edit or eliminate all nucleic acid
replication
Result 1-5 mutations in each new replication
cycle
Result – Each new virus is different from the
others
New virus is being reproduced 1-10 BILLION
times per day
Thus, 1-10 BILLION mutations being produced
DAILY
Protease Inhibitor Resistance
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HIV continues to mutate
Also getting cross resistance
Darwinian models are very applicable with
HIV
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Weak strains die out, stronger strains survive
and replicate.
Many mutations probably exist before a
drug is taken
Therapy Must Address
Resistance Issues
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Maximize the suppression of viral
replication.
Use combination therapies requiring HIV
to create multiple drug mutations for
resistance
Force the emergence of strains with
slower replication or decreased virulence
New Therapies
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Entry inhibitors
Designed to block the virus from entering
the cell
Fusion Inhibitors
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Pentafuside (T-20)
Integrase Inhibitors
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Prevents HIV DNA from entering human
DNA
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Zintevir (AR-177)
Zinc Finger Inhibitors
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Disrupts polyprotein formation essential
for HIV replication.
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Benzamide-Disulfide
Final Issues
Demise of Monotherapy
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Use of single drugs leads to drug resistance
Today, combinations usually include
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Two reverse transcriptase inhibitors
One Protease Inhibitor
Combination of three or more drugs called
HAART - Highly Active Anti-retroviral
Therapy
Result of HAART
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Only one RNA strand out of 1 trillion strands
caries resistance to all three drugs at the same
time.
Problem
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1-10 billion genetically different strands are produced
each day
Strands can exchange nucleotides (recombination)
Result- Resistance to HAART cocktails
Results of Resistance
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30% of newly infected individual are
carrying forms of HIV that are resistant to
at least one drug.
10% are resistant to 2 drugs used in
combination.
60% of patients experience HIV
suppression failure during first line
antiviral drug treatment
Salvage Therapy
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Is the use of drugs to suppress viral
replication when standard therapy fails.
Some patients are taking 10 of the 15
drugs at one time to SUPPRESS HIV
replication.
In USA 30-50% of individuals are in
Salvage therapy (Stein)
Problem- is not proving effective.
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70-80% experience salvage or second line
drug treatment failure.
Final Issues
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New strains from people in high risk having sex together.
Behaviors that rapidly increased HIV have returned
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Individuals in minority communities that do not identify
themselves as Gay have high-risk behavior and transmit
HIV to their heterosexual partners
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Bathhouses
Sex Clubs
Barebacking
Individuals engaging in the “Down Low”
Bug Catchers
Glorification of being “Positive
No realization of problems with being Positive
Future
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More people will get the disease
Costs to society will increase – Who pays?
Africa, Eastern Europe, Asia,
IDU’s