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HIV/AIDSHIV/AIDS

Human Immunodeficiency VirusHuman Immunodeficiency Virus

Acquired Immunodeficiency Acquired Immunodeficiency SyndromeSyndrome

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AIDS is Caused by HIVAIDS is Caused by HIV

Is the one common denominator Is the one common denominator within a range of populations.within a range of populations.

Has been identified by electron Has been identified by electron microscopy.microscopy.

Antibodies, viral antigens, and HIV Antibodies, viral antigens, and HIV RNA have been found in HIV-Positive RNA have been found in HIV-Positive and AIDS patients.and AIDS patients.

Many othersMany others

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More Origins of HIVMore Origins of HIV Unidentified Flying Objects (UFO’s) coming from Unidentified Flying Objects (UFO’s) coming from

spacespace Is a biological weapon designed to kill non-whites.Is a biological weapon designed to kill non-whites. Came from domestic cats. (Feline AIDS is similar Came from domestic cats. (Feline AIDS is similar

to Human AIDS)to Human AIDS) HIV Contaminated _______ vaccines.HIV Contaminated _______ vaccines.

PolioPolioSmallpoxSmallpoxTetanus Tetanus Hepatitis Hepatitis

African Green MonkeyAfrican Green Monkey African PeopleAfrican People African Cattle, Pigs, SheepAfrican Cattle, Pigs, Sheep CIA and other spy agenciesCIA and other spy agencies Biological Weapons LabsBiological Weapons Labs

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Current TheoryCurrent Theory Hahn et al. (1999, 2000)Hahn et al. (1999, 2000) Simian virus closely related to HIV jumped from Simian virus closely related to HIV jumped from

chimps to humans .chimps to humans . Virus then mutated into its current form.Virus then mutated into its current form. EvidenceEvidence

– Genes from all four SIVcpz isolates cluster to their Genes from all four SIVcpz isolates cluster to their subspecies or originsubspecies or origin Pan Troglodytes Troglodytes - West AfricaPan Troglodytes Troglodytes - West Africa Pan Trogldytes Scheinfurthii - East AfricaPan Trogldytes Scheinfurthii - East Africa

– All known HIV-1 strains cluster with W. Africa Chimp All known HIV-1 strains cluster with W. Africa Chimp virusesviruses

– Evidence of genetic recombination among SIVcpz strains Evidence of genetic recombination among SIVcpz strains of the Troglodytes lineage. of the Troglodytes lineage.

Newer evidence indicates multiple jumpings – Newer evidence indicates multiple jumpings – different strainsdifferent strains

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ExampleExample

HIV Strains have 11 distinct HIV Strains have 11 distinct subtypessubtypes

– A-KA-K– Subtype B is dominant in US and Subtype B is dominant in US and

EuropeEurope– Subtype D is dominant in AfricaSubtype D is dominant in Africa

Virus mutates rapidly. Virus mutates rapidly.

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United States HIV HistoryUnited States HIV History

Virus has been in the US since mid. 1970’s.Virus has been in the US since mid. 1970’s.– 1979-1981 1979-1981 – Physicians in New York and Los Angeles began Physicians in New York and Los Angeles began

reporting particular diseases in Gay males.reporting particular diseases in Gay males.– Including:Including:

Rare PneumoniasRare Pneumonias Cancers Cancers Other diseases Other diseases

– Diseases were not usually found in people with Diseases were not usually found in people with healthy immune systems.healthy immune systems.

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19821982 Public Health begins using term Acquired Public Health begins using term Acquired

Immunodeficiency Syndrome (AIDS) to Immunodeficiency Syndrome (AIDS) to describe opportunistic infections in describe opportunistic infections in previously healthy men.previously healthy men.– IncludingIncluding

Kaposi’s SarcomaKaposi’s Sarcoma Pneumocystis Carni PneumoniaPneumocystis Carni Pneumonia

Surveillance of AIDS beginsSurveillance of AIDS beginsDiagnosis of cellular immune deficiencyDiagnosis of cellular immune deficiencyAbsence of an underlying causeAbsence of an underlying causeReduced resistance to the diseaseReduced resistance to the disease

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HIV SurveillanceHIV Surveillance

Definition modified in 1983Definition modified in 1983 Required to be reported to CDCRequired to be reported to CDC

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19831983 First cases of AIDS in heterosexuals are First cases of AIDS in heterosexuals are

documented.documented. Virus is isolated by various labs.Virus is isolated by various labs. NamedNamed

– HTLV-III (Human T-Lymphotrophic Virus-III)HTLV-III (Human T-Lymphotrophic Virus-III) (Gallo)(Gallo)

– LAVLAV (Lymphadenopathy Associated Virus) (Lymphadenopathy Associated Virus) (Luc Montagnier Mont-Tan-Ya)(Luc Montagnier Mont-Tan-Ya)

– ARVARV (AIDS – Related Virus) (AIDS – Related Virus)

Ultimately named Ultimately named – HIV HIV (Human Immunodeficiency Virus) (Human Immunodeficiency Virus)

(Sub-committee of the Committee on the (Sub-committee of the Committee on the Taxonomy of Taxonomy of

VirusesViruses

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19851985 Second type of HIV discoveredSecond type of HIV discovered

– HIV-2HIV-2 Related to SIV Related to SIV Not as related to HIV-1Not as related to HIV-1 Does not seem as harmful as HIV-1Does not seem as harmful as HIV-1 Reproduces slower than HIV-1Reproduces slower than HIV-1

Screening tests become availableScreening tests become available Tests of stored blood samples indicate HIV Tests of stored blood samples indicate HIV

was being transmitted in US and Europe in was being transmitted in US and Europe in mid to late 1970’s.mid to late 1970’s.

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Early Definitions of AIDS Early Definitions of AIDS 1981-931981-93

Many definitions of AIDSMany definitions of AIDS ProblemProblem

– Social Security Administration (SSA)Social Security Administration (SSA)– Used AIDS definition to determine Used AIDS definition to determine

disabilitydisability Symptoms were based on opportunistic Symptoms were based on opportunistic

infections in men.infections in men.

– ResultResult 65% of women were excluded65% of women were excluded Other problems tooOther problems too

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19931993

New definition of AIDSNew definition of AIDS Emphasized the importance of T4 Emphasized the importance of T4

lymphocyte counts.lymphocyte counts. Added other diseasesAdded other diseases System becomes simplerSystem becomes simpler

Also allowed one to become diagnosed Also allowed one to become diagnosed with AIDS but remain symptom-free of with AIDS but remain symptom-free of diseases.diseases.

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19871987

First case of HIV-2 in the U.S.First case of HIV-2 in the U.S. First Anti - HIV drugs become First Anti - HIV drugs become

availableavailable– Zidovudine (AZT)Zidovudine (AZT)

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19881988

Protease Inhibitors are identified.Protease Inhibitors are identified. Have problems with Have problems with

– AbsorptionAbsorption– Have rapid liver metabolismHave rapid liver metabolism– Insolubility Insolubility

Result – More development and Result – More development and clinical clinical trials. trials.

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19921992

Protease Inhibitors (PI) become more Protease Inhibitors (PI) become more developeddeveloped

First - Saquinavir Mesylate (Invirase)First - Saquinavir Mesylate (Invirase)– Was used in combination with other drugsWas used in combination with other drugs– Minimal clinical trial dataMinimal clinical trial data– Had poor absorptionHad poor absorption– Was the least potent of other PI’s that came on Was the least potent of other PI’s that came on

the market later.the market later.

Second – Ritonavir (Norvir)Second – Ritonavir (Norvir)

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More Protease Inhibitors are More Protease Inhibitors are DevelopedDeveloped

Saquinavir Saquinavir (Fortovase) (Fortovase) – More easily absorbed by the bodyMore easily absorbed by the body

IndinavirIndinavir (Crixivan)(Crixivan)– Most often usedMost often used

NelfinavirNelfinavir (Viracept)(Viracept) AmprenavirAmprenavir (Agenerase)(Agenerase) ABT – 378ABT – 378 (Kaletra)(Kaletra)

Problem Problem – Drugs are expensive $450-$700/month Drugs are expensive $450-$700/month – = $5,400 - $8,400/yr= $5,400 - $8,400/yr

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20002000

Drug Combinations (Cocktails)Drug Combinations (Cocktails)– Uses multiple combinations of Uses multiple combinations of

drugsdrugs– Called Highly Active Antiretroviral Called Highly Active Antiretroviral

TherapyTherapy

(HAART)(HAART)

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20012001

Negotiations to reduce costsNegotiations to reduce costs Generics are developed by outside Generics are developed by outside

countries despite patent laws.countries despite patent laws.– Is a major problemIs a major problem

Costs go down Costs go down Drug companies reevaluate staying Drug companies reevaluate staying

in the HIV drug marketin the HIV drug market When do you use (early vs. later)When do you use (early vs. later)

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PresentPresent HIV continues to mutateHIV continues to mutate

– Currently getting HIV resistance to Currently getting HIV resistance to drugsdrugs

People are returning to previous People are returning to previous lifestyles lifestyles – Drugs are effective at helping Drugs are effective at helping

peoplepeople– Can workCan work– Enjoy lifeEnjoy life

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Also Also People are not taking drug combinations so they effectively People are not taking drug combinations so they effectively

block the virusblock the virus– MonotherapyMonotherapy

People also stop taking drugs when they do not have moneyPeople also stop taking drugs when they do not have money

People stop taking drugs when they are feeling betterPeople stop taking drugs when they are feeling better

People who are infected are having sex with other infected People who are infected are having sex with other infected individualsindividuals

Has spread into the IDU community which is spreading it into Has spread into the IDU community which is spreading it into the general heterosexual population.the general heterosexual population.

ResultResult

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1. Drug Resistance1. Drug Resistance

30% of newly infected individuals 30% of newly infected individuals have viral forms that resistant to at have viral forms that resistant to at least one drug.least one drug.

Drug resistant strains are becoming Drug resistant strains are becoming more powerfulmore powerful

Result – Salvage therapyResult – Salvage therapy– Give everything you can Give everything you can – 30-50% of HIV infected persons are in 30-50% of HIV infected persons are in

such therapy. such therapy.

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2. New Strains2. New Strains

Are more powerful than previous Are more powerful than previous strainsstrains

Cause individuals who are doing well Cause individuals who are doing well on drug cocktails to become ill againon drug cocktails to become ill again

Has caused us to reevaluate the Has caused us to reevaluate the issues of vaccinesissues of vaccines

Is going to become a real problemIs going to become a real problem

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Conclusions and IssuesConclusions and Issues

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HIV is a Unique DiseaseHIV is a Unique Disease

Affects mostly young and middle Affects mostly young and middle aged adults.aged adults.

Are sexually activeAre sexually active Are in their prime productive and Are in their prime productive and

reproductive yearsreproductive years Impact is demographic, economic, Impact is demographic, economic,

political, and social.political, and social.

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ProblemProblem

Have forgotten the pastHave forgotten the past STD rates are increasing again in STD rates are increasing again in

some communitiessome communities 1999-2002 number of males with 1999-2002 number of males with

new HIV infections increased 7.3% new HIV infections increased 7.3% (CDC, 2003)(CDC, 2003)– Among MSMs increased 17%Among MSMs increased 17%

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HIV Is A Preventable HIV Is A Preventable DiseaseDisease

To stop the disease, must change the To stop the disease, must change the behavior.behavior.

Is a system of numbers.Is a system of numbers.– More people in a population that have it,More people in a population that have it,– The greater the likelihood YOU (or your The greater the likelihood YOU (or your

offspring) will get it.offspring) will get it.

1/100 vs. 10/100 vs. 25/100 vs. 50/1001/100 vs. 10/100 vs. 25/100 vs. 50/1001/1001/100 1/10 1/4 1/21/10 1/4 1/2 1%1% 10% 10% 25%25% 50% 50%