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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



  • 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


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.


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


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


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





Result different lengths of protein that perform different tasks
ResultDifferent Lengths of Protein that Perform Different Tasks



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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