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HIV Disease. Transmission Variables. How easily a virus can enter the body Influenza and SARS enter by respiratory tract Easy to infect HIV is hard to enter the body. Usually needs sexual contact Encounter rates

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transmission variables
Transmission Variables
  • How easily a virus can enter the body
    • Influenza and SARS enter by respiratory tract
    • Easy to infect
    • HIV is hard to enter the body. Usually needs sexual contact
  • Encounter rates
    • The number of opportunities that an uninfected person has with an infected person
    • More contacts, the higher the probability of becoming infected.
  • Population density
    • 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
      • Sickle Cell Anemia – Good for Malaria.
more variables
More Variables
  • Percent of people with the disease in a population or subpopulation.
    • 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.
  • Duration of lifespan before death
    • Rapid death, fewer people to pass on the virus
    • Ebola
  • Geographic Isolation
    • If isolated, fewer people can become exposed
    • Difficult with global transportation SARS
risk behaviors
Risk Behaviors
  • ANY BEHAVIOR THAT RESULTS IN THE TRANSMISSION OF BODY FLUIDS PLACES A PERSON AT HIGH RISK FOR BBPS
    • HIV
    • Hepatitis
    • STD’s
routes of transmission
ROUTES OF TRANSMISSION
  • Sexual transmission
  • Blood contact during needle sharing
  • Perinatally
    • Mother to baby before or during delivery
  • Blood Transfusions
    • Rare in US today
    • Higher in third world
  • Other
slide7
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
overview
Overview
  • Is a slow virus
    • Allows the virus to pass on its genetic codes to many people.
  • Mutates rapidly
    • Uses the bodies DNA to hide
    • Uses other processes
  • Does not kill the host for a long period
    • Not like Ebola which kills the host in a couple of weeks
  • Result – From a virus standpoint, is an ideal virus
slide10
HIV Infection Occurs

Acute Retroviral Syndrome Occurs

Antibodies Develop

Asymptomatic

Symptomatic HIV Disease

AIDS

Death

initial infection
Initial Infection
  • 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.
    • Use full battery of HIV drug cocktails
      • See MMWR
    • Will not be used for general risk populations
      • IDU’s
      • MSM’s
    • May be used for medical exposure or other reasons
      • Needle stick
      • Rape
    • Drug cocktails do not work for other STDs or Hepatitis
acute retroviral syndrome
Acute Retroviral Syndrome
  • Usually occurs in 2-4 weeks
  • May occur up to 12 weeks
  • Symptoms
    • Fever, body aches, sore throat, headache malaise
    • Diarrhea, swollen lymph nodes, others
  • May feel like a case of the flu.
  • Treat symptomatically
    • ASA, bed rest, etc.
  • Symptoms usually last 1-2 weeks then go away
inside the body
Inside the Body
  • Virus is being widely disseminated
  • High levels of the virus initially occurred then drop off.
    • No immune response yet to combat it
  • Antibody production begins
    • Destroys lots of the virus but not all
    • Virus infects Thelper Lymphocytes
  • Virus continues to replicate in lymph tissue
antibody development
Antibody Development
  • Begins about 2-3 weeks
    • 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
    • Several tests
      • Viral culturing
      • PCR Polymerase Chain Reaction
      • Reverse Transcriptase
      • Others
asymptomatic stage
Asymptomatic Stage
  • 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
Some Symptoms
  • Recurrent swollen lymph glands
  • Diarrhea
  • Fever
  • Weight loss
  • Oral and Vaginal Yeast infections
  • Others
    • Symptoms can also result from other diseases
    • Bacteria
    • Fungus
    • Parasites
behaviors
Behaviors
  • 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
Chronic Symptomatic HIV Disease
  • Immune system is being further deteriorated
    • T4 or CD4+ cells decrease
  • Symptoms become more frequent
  • Symptoms last longer
  • Ultimately overwhelms lymphatic system
    • 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.
slide19
AIDS
  • Diagnosed when the following occurs
    • 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
Some Opportunistic Infections
  • Pneumocystis Carinii Pneumonia
  • Kaposi’s sarcoma
  • Recurrent Pneumonia
  • Candidiasis
  • Toxoplasmosis of the Brain
many other disorders as well
Many Other Disorders as Well
  • Wasting Syndrome
  • Candidiasis of bronchi, trachea, lungs, esophagus
  • Cytomegalovirus
  • Encephalopathy
  • Histoplasmosis
  • Lymphoma’s
  • Many others
with aids
With Aids
  • 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
Physical Issues
  • Persons become debilitated by symptoms
  • Commonplace behaviors become difficult
    • Hard to have steady employment
    • May have difficulty shopping for food
    • Hard to do chores at home
psychological neurological issues
Psychological/Neurological Issues
  • 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
AIDS-Related Dementia
  • Solely associated with AIDS
  • Early symptoms
    • Forgetfulness
    • Recent memory loss
    • Loss of concentration
    • Loss of thought
    • Movement problems - balance
late symptoms
Late Symptoms
  • Loss of speech
  • Fatigue
  • Bladder and bowel incontinence
  • Seizures
  • Coma
  • Death
some neurological problems associated with hiv infection
Some Neurological Problems Associated with HIV Infection
  • Asymptomatic infection – no mental impairment
  • AIDS Dementia Complex (ADC)
  • Acute Encephalitis
  • Aseptic Meningitis
  • Distal sensory neuropathy
treatment
Treatment
  • PREVENTION IS THE BEST TREATMENT
  • After becoming infected
  • Keep the immune system from becoming taxed
    • Your genetics is important
    • Good nutrition
    • Exercise
    • Counseling if necessary
    • Peer support network
    • Social Services Support
    • Drugs
drugs
Drugs
  • Are designed to target virus replication at different points
hiv virus
HIV VIRUS
  • Reverse Transcriptase ssRNA
slide31
CD4 Receptor

HIV

VIUS

Reverse Transcriptase

CC-CKR-5

CXCKR-4

(fusin)

ss DNA

Genome

RNA

ds DNA

RT

Viral RNA

Mature

HIV

MRNA

Protease

HIV Bud

Viral Proteins

slide32
CD4 Receptor

VIRUS

ss DNA

ds DNA

Genome

RNA

1

RT

Viral RNA

Mature

HIV

MRNA

2

Add

Protease

HIV Bud

Viral Proteins

reverse transcriptase inhibitors
Reverse Transcriptase Inhibitors
  • Two groups
    • Nucleoside Analogs
    • Non-Nucleoside Analogs
    • Generally are designed to interfere with the viruses ability to replicate itself
nucleoside analogs
Nucleoside Analogs’
  • 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
non nucleoside compounds
Non Nucleoside Compounds
  • 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
    • Unlike Nucleoside compounds do not incorporate into the DNA
    • Instead, binds directly to the RT
problem
Problem
  • Initially worked
  • HIV resistant strains developed in weeks
  • Better results when used in combination
    • 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
Examples of Side effects
  • Liver Toxicity Nevirapine (Viramune)
  • Rash
other problems
Other Problems
  • 15% of HIV infected people cannot tolerate nucleoside or non-nucleoside compounds.
  • Both groups are time limited for effectiveness.
protease inhibitors
Protease Inhibitors
  • Newest line of defense
  • HIV protease generally cuts viral strands
  • Is essential for viral replication
  • PI basically stop the virus from maturing
    • Blocks the binding and cutting sites for viral protease
  • Result- Virus not cut – cannot replicate
  • Also indirectly decrease the production of RT
slide47
Result, No Cleavage

HIV Remains Immature and Cannot Replicate

drug resistant nucleoside analog mutations
Drug-Resistant Nucleoside Analog Mutations
  • 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
Protease Inhibitor Resistance
  • HIV continues to mutate
  • Also getting cross resistance
  • Darwinian models are very applicable with HIV
    • Weak strains die out, stronger strains survive and replicate.
  • Many mutations probably exist before a drug is taken
therapy must address resistance issues
Therapy Must Address Resistance Issues
  • 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
New Therapies
  • Entry inhibitors
  • Designed to block the virus from entering the cell
  • Fusion Inhibitors
    • Pentafuside (T-20)
integrase inhibitors
Integrase Inhibitors
  • Prevents HIV DNA from entering human DNA
    • Zintevir (AR-177)
zinc finger inhibitors
Zinc Finger Inhibitors
  • Disrupts polyprotein formation essential for HIV replication.
    • Benzamide-Disulfide
demise of monotherapy
Demise of Monotherapy
  • Use of single drugs leads to drug resistance
  • Today, combinations usually include
    • Two reverse transcriptase inhibitors
    • One Protease Inhibitor
  • Combination of three or more drugs called HAART - Highly Active Anti-retroviral Therapy
result of haart
Result of HAART
  • Only one RNA strand out of 1 trillion strands caries resistance to all three drugs at the same time.
  • Problem
    • 1-10 billion genetically different strands are produced each day
    • Strands can exchange nucleotides (recombination)
    • Result- Resistance to HAART cocktails
results of resistance
Results of Resistance
  • 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
Salvage Therapy
  • 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.
    • 70-80% experience salvage or second line drug treatment failure.
final issues1
Final Issues
  • New strains from people in high risk having sex together.
  • Behaviors that rapidly increased HIV have returned
    • Bathhouses
    • Sex Clubs
    • Barebacking
  • Individuals in minority communities that do not identify themselves as Gay have high-risk behavior and transmit HIV to their heterosexual partners
    • Individuals engaging in the “Down Low”
  • Bug Catchers
  • Glorification of being “Positive
  • No realization of problems with being Positive
future
Future
  • More people will get the disease
  • Costs to society will increase – Who pays?
  • Africa, Eastern Europe, Asia,
  • IDU’s
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