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HIV / AIDS – 2006HIV / AIDS – 2006
An Overview for International An Overview for International VolunteersVolunteers
Allen McCutchan, MD, MScAllen McCutchan, MD, MScProfessor Of MedicineProfessor Of Medicine
UCSDUCSD
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Outline of Lecture Origins of HIV Origins of HIV
Virology and Clinical Features of HIV Virology and Clinical Features of HIV
infectioninfection
History of AIDS Epidemic History of AIDS Epidemic
Responses to the HIV EpidemicResponses to the HIV Epidemic
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Origins of HIV From SIV chimpanzee
Humans and chimps share ~ 98 % DNA sequences
HIV from humans is similar to SIV found in chimps
HIV transferred from chimps to man in 1920s - 30s
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Origins of HIV From SIV chimpanzee
Group M (main) HIV-1, the cause of the AIDS epidemic, passed Group M (main) HIV-1, the cause of the AIDS epidemic, passed
from chimps to humans in the ~ 1920s or 1930sfrom chimps to humans in the ~ 1920s or 1930s
HIV-1 emerged from Africa in the ~ mid 1970’s and was spread HIV-1 emerged from Africa in the ~ mid 1970’s and was spread
to Europe and American by gay mento Europe and American by gay men
HIV-2 , a less virulent retrovirus related to SIV HIV-2 , a less virulent retrovirus related to SIV African green monkeyAfrican green monkey
is epidemic in West Africais epidemic in West Africa
Chimp to human transmission of HIV on 2 other occasions Chimp to human transmission of HIV on 2 other occasions
created related HIV-1 minor groups O and Ncreated related HIV-1 minor groups O and N
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HIV may have infected the first persons thru “bushmeat”
Killing, butchering, and Killing, butchering, and
preparing primates preparing primates
exposes people to exposes people to
simian (monkey) simian (monkey)
viruses that are more viruses that are more
deadly to people than deadly to people than
to monkeysto monkeys
E2
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Evolutionary Relationships of Evolutionary Relationships of Primate Retroviruses Related to HIVPrimate Retroviruses Related to HIV
HIV -1 N
SIV = simian (primate) HIV = human
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HIV Clades
HIV rapidly evolves by two mechanisms: HIV rapidly evolves by two mechanisms: – Mutation - changes in single nucleosides of the RNA Mutation - changes in single nucleosides of the RNA – Recombination – combinations of long RNA Recombination – combinations of long RNA
sequences from two distinct HIV strainssequences from two distinct HIV strains
Distinct clades (genetic subgroups) of the M group of Distinct clades (genetic subgroups) of the M group of
HIV have evolved and become dominate in specific HIV have evolved and become dominate in specific
geographic regionsgeographic regions– A in Central Africa A in Central Africa – B in North American and EuropeB in North American and Europe– C in Southern and Eastern AfricaC in Southern and Eastern Africa
Several clades (eg, A/G ad A/E) are recombinantsSeveral clades (eg, A/G ad A/E) are recombinants
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Distribution of HIV-1 Cladesin Sub-Saharan Africa
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Faces of HIV / AIDS Russian Mother and Daughter
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Scanning Electron Micrograph and Cartoon of the Structure of an HIV
Virion
External envelop proteins
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HIV replication cycleHIV replication cycle
Capsidproteinsand viral
RNA
CD4Receptor
Viral RNA
New HIV virions
Protease
Attachment UncoatingReverse
Transcription Integration Transcription Translation
ReverseTranscriptase
Double stranded DNA copy
Integratedviral DNA
ViralmRNA
Integrase
Polyprotein
1 2 3 4 5 6Assembly and
Release
Nucleus
Cellular DNA
HIV Virions
HIV virion
7
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Budding of HIV from CD4 Cell
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LABORATORY MARKERS OF HIV INFECTION
CD4 lymphocyte countCD4 lymphocyte count (“T cells”) (“T cells”) 1) 1) Measures immunologic damage by HIVMeasures immunologic damage by HIV
(strength of immune system)(strength of immune system)
2) 2) Measured by a cytographMeasured by a cytograph (medium tech (medium tech and available in most developing countries)and available in most developing countries)
3) 3) Normal ValuesNormal Values = 600-1200 = 600-1200
4) 4) CD4 below 200CD4 below 200 increases risk of increases risk of infectionsinfections
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Cytograph in Ethiopian Army Hospital Laboratory
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LABORATORY MARKERS OF HIV INFECTION
Viral loadViral load (or HIV RNA Levels) (or HIV RNA Levels)
1) Measures concentration of HIV in 1) Measures concentration of HIV in blood and expressed in logarithms blood and expressed in logarithms
100 = 2 logs 100 = 2 logs 100,000 = 5 logs)100,000 = 5 logs)
2 ) Measured by high tech PCR Assay 2 ) Measured by high tech PCR Assay and thus, not widely available in developing and thus, not widely available in developing countriescountries
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LABORATORY MARKERS OF HIV INFECTION
UsesUses of “viral load” of “viral load”
a) Diagnosis - detects primary (early) infection before antibodies to HIV appear
b) Prognosis - predicts CD4 decline, clinical events, and time to death
c) Monitoring treatment – measures effects of drugs
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Dynamics of HIV Infections
Rapid HIV productionRapid HIV production and human cell and human cell destructiondestruction without treatment without treatment– About 10About 101010 (10 billion) virions are produced (10 billion) virions are produced
daily daily – Average life-span of HIV in plasma (free Average life-span of HIV in plasma (free
virus) is ~ 6 hours virus) is ~ 6 hours – Average life-span of an HIV-infected CD4 Average life-span of an HIV-infected CD4
lymphocytes is ~ 1.6 dayslymphocytes is ~ 1.6 days Long HIV latency and survivalLong HIV latency and survival in human cells in human cells
– HIV lies dormant even during treatment, but HIV lies dormant even during treatment, but can revive if treatment is stopped, making can revive if treatment is stopped, making cures impossible thus farcures impossible thus far
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PATHOGENESIS OF HIV INFECTION: Anatomic Compartments of HIV
T h e P a th o g e n e s is o f H IV -1 In fe c t io n :C o m p a r tm e n ts
C o lo n , D u o d e n u m a n dR e c tu m C h ro m a ffin C e lls
L y m p h o c y te s in B lo o d ,S e m e n a n d V a g in a l F lu id
S k in L a n g e rh a n s ’ C e lls
B o n e M a rro w
B ra in M a c ro p h a g e sa n d G lia l C e lls
L y m p h N o d e s
T h y m u s G la n d
L u n g A lv e o la rM a c ro p h a g e s
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General Mechanisms of HIV Pathogenesis
Direct injuryDirect injury– Nervous system (encephalopathy and peripheral Nervous system (encephalopathy and peripheral
neuropathy)neuropathy)– Kidney (HIVAN = HIV-associated nephropathy)Kidney (HIVAN = HIV-associated nephropathy)– Heart (HIV cardiomyopathy) Heart (HIV cardiomyopathy) – Testes/ovary (hypogonadism in both sexes)Testes/ovary (hypogonadism in both sexes)– Bowel (diarrrhea and malabsorption)Bowel (diarrrhea and malabsorption)
Indirect injury thru immunosuppressionIndirect injury thru immunosuppression– Opportunistic infections and tumorsOpportunistic infections and tumors
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General principles of Immune Dysfunction in HIV
Marked disruption of immune tissues (lymph nodes)Marked disruption of immune tissues (lymph nodes) Most cell types of the immune system are Most cell types of the immune system are
dysfunctionaldysfunctional Persons with advanced HIV (AIDS) have Persons with advanced HIV (AIDS) have
– Impaired ability to respond to new infections or Impaired ability to respond to new infections or vaccinesvaccines
– Impaired ability to maintain memory responses to Impaired ability to maintain memory responses to old infectionsold infections
– Susceptibility to opportunistic infections Susceptibility to opportunistic infections – Loss of containment of HIV replication Loss of containment of HIV replication
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Relating Disease Progression to Plasma HIV-1 RNA Level and CD4 Cell Count
Viral Load
1,000
10,000
100,000
100
CD4 COUNT
1000 900 800 700 600500
400
300
200
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PATHOGENISIS OF HIV INFECTION:No Progression With Low Level Viremia
CD4
RNA
Primary HIV Chronic Non-progressive HIV Infection
RNA Set Point ~ 103
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PATHOGENISIS OF HIV INFECTION:Average Progression With Median Level Viremia
RNA
CD45
Primary HIV Slowly Progressive HIV AIDS
Years
1 10
RNA Set Point ~104
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PATHOGENISIS OF HIV INFECTION:Rapid Progression With High Level Viremia
RNA
CD4
32
Primary HIV AIDS
Years
RNA Set Point ~ 106
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STAGES OF HIV INFECTION
Primary HIV InfectionPrimary HIV Infection– Mononucleosis - like illness in about Mononucleosis - like illness in about 50% of patients50% of patients
• Symptoms - fever, fatigue, lymph nodes swelling, rash, or meningitis
• ELISA for HIV antibodies may be briefly (2-6 weeks) negative, but high levels of viremia (> 10 6 copies / ml)
– Higher levels of viremia predict: Higher levels of viremia predict:
• severe symptoms during primary infection
• rapid progression to AIDS
• high infectivity for sexual partners
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STAGES OF HIV INFECTION
Asymptomatic Chronic Infection (Stage A)Asymptomatic Chronic Infection (Stage A)– Not always asymptomaticNot always asymptomatic - patients may be vigorously healthy - patients may be vigorously healthy
or have mild fatigue or low grade fevers (eg, occasional night or have mild fatigue or low grade fevers (eg, occasional night sweats), but no illnesses indicating immunosuppressionsweats), but no illnesses indicating immunosuppression
– CD4 countsCD4 counts may range from normal (>500) to very low (<50) may range from normal (>500) to very low (<50)– Plasma HIV RNA levelsPlasma HIV RNA levels are highly variable (5,000 to > 10 are highly variable (5,000 to > 1066))
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STAGES OF HIV INFECTION
Symptomatic Chronic Infection (Stages B and C)Symptomatic Chronic Infection (Stages B and C)– BB = History of “Minor” Opportunistic Infections (eg oral = History of “Minor” Opportunistic Infections (eg oral
candidiasis or recurrent Herpes zoster) - see appendix 1 to lecture candidiasis or recurrent Herpes zoster) - see appendix 1 to lecture outlineoutline
– CC = History of AIDS defining opportunistic infections or = History of AIDS defining opportunistic infections or tumors (eg, pneumocystis pneumonia or Kaposi Sarcoma) - see tumors (eg, pneumocystis pneumonia or Kaposi Sarcoma) - see appendix 2 to lecture outlineappendix 2 to lecture outline
– AIDSAIDS (Acquired Immunodeficiency Syndrome) (Acquired Immunodeficiency Syndrome) = either less = either less than 200 CD4than 200 CD4+ + T cells/µL or Stage C (history of any category AIDS T cells/µL or Stage C (history of any category AIDS
defining condition)defining condition)
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CAUSES OF MORBIDITY AND MORTALITY
Without sophisticated medical treatmentWithout sophisticated medical treatment::
1. In much of the underdeveloped world, 1. In much of the underdeveloped world,
opportunistic infections (esp, tuberculosis and opportunistic infections (esp, tuberculosis and
diarrheal diseases) are often the first and fatal events diarrheal diseases) are often the first and fatal events
2. Both lead to wasting, malnutrition, and death 2. Both lead to wasting, malnutrition, and death
from starvation, dehydration, and secondary from starvation, dehydration, and secondary
pneumoniaspneumonias
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HIV replication cycle and sites of drug activityHIV replication cycle and sites of drug activity
CD4Receptor
Viral RNA
New HIVparticles
Protease
Attachment Uncoating ReverseTranscription
Integration Transcription Translation
ReverseTranscriptase
Unintegrateddouble strandedViral DNA
Integratedviral DNA
ViralmRNA
Integrase
gag-polpolyprotein
1 2 3 4 56
Assembly andRelease
Protease InhibitorsIndinavir (Crixivan)Ritonavir (Norvir)
Saquinavir (Fortovase)Nelfinavir (Viracept)
Amprenavir (Angenerase)Lopinavir / ritonavir
(Kaletra)Atazanavir (Reyataz)Tripanavir (Aptivus)
Darunavir
NRTIsAZT (Zidovudine-Retrovir)
ddI (Didanosine-Videx)ddC (Zalcitabine-Hivid)d4T (Stavudine-Zerit)
3TC (Lamivudine-Epivir)ABC(Abacavir-Ziagen)
FTC (Emtricitabine, Emtriva)
NNRTIsEfavirenz (Sustiva)
Delavirdine (Rescriptor)Nevirapine (Viramune)
Nucleus
Cellular DNA
HIV Virions
nRTITenofovir DF
(Viread)
Fusion Inhibitors (Enfuvirtide,
Fuzeon)
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Current treatment options: Nucleoside Reverse Transcriptase Inhibitors
(NRTIs)• AZT (Zidovudine-Retrovir)AZT (Zidovudine-Retrovir)• ddI (Didanosine-Videx)ddI (Didanosine-Videx)• ddC (Zalcitabine-Hivid)ddC (Zalcitabine-Hivid)• d4T (Stavudine-Zerit)d4T (Stavudine-Zerit)• 3TC (Lamivudine-Epivir)3TC (Lamivudine-Epivir)• ABC (Abacavir-Ziagen)ABC (Abacavir-Ziagen)• FTC (Emtricitabine, Emtriva)FTC (Emtricitabine, Emtriva)• TFV (Tenofovir DF, Viread)TFV (Tenofovir DF, Viread)
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Current treatment options: Non Nucleosides (NNRTIs)
• Nevirapine (Viramune)Nevirapine (Viramune)• Efavirenz (Sustiva)Efavirenz (Sustiva)• Delavirdine (Rescriptor)Delavirdine (Rescriptor)
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Current treatment options: Protease Inhibitors (PIs) PIs
– Indinavir (Crixivan)Indinavir (Crixivan)– Ritonavir (Norvir)Ritonavir (Norvir)– Saquinavir (Fortovase)Saquinavir (Fortovase)– Nelfinavir (Viracept)Nelfinavir (Viracept)– Amprenavir (Agenerase)Amprenavir (Agenerase)– Lopinavir/ritonavir (Kaletra)Lopinavir/ritonavir (Kaletra)– Atazanavir (Reyataz)Atazanavir (Reyataz)– Tipranavir (Aptivus)Tipranavir (Aptivus)– Darunavir (TMC114)Darunavir (TMC114)
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Principles of Antiretroviral Therapy
Give ARVs in combinations of 2-4 drugs for Give ARVs in combinations of 2-4 drugs for
adequate potency to completely suppress HIV adequate potency to completely suppress HIV
replication replication
Maintain adherence > 95-98 % to avoid Maintain adherence > 95-98 % to avoid – failure of suppressionfailure of suppression of HIV replication of HIV replication– selection of drug resistant HIVselection of drug resistant HIV because because
patients failing twice don’t often respond to patients failing twice don’t often respond to further changes in ARVsfurther changes in ARVs
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Principles of Antiretroviral Therapy
Monitor patients regularly (every 2-6 months) Monitor patients regularly (every 2-6 months)
for:for:– Symptoms of opportunistic infections (OIs Symptoms of opportunistic infections (OIs
such as TB ) and tumors (such as such as TB ) and tumors (such as lymphoma or Kaposi’s Sarcoma)lymphoma or Kaposi’s Sarcoma)
– Toxicity (blood tests and symptoms)Toxicity (blood tests and symptoms)– Adherence (question about taking ARV Adherence (question about taking ARV
generally and in detail for the past 3 days)generally and in detail for the past 3 days)
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Principles of Antiretroviral Therapy
Monitor patients for Monitor patients for – Symptoms of toxicity (blood tests and Symptoms of toxicity (blood tests and
symptoms)symptoms)– Adherence (question about taking ARV Adherence (question about taking ARV
generally and in detail for the past 3 days)generally and in detail for the past 3 days)– Use of other drug that might change Use of other drug that might change
metabolism of ARV drugsmetabolism of ARV drugs
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Causes of Treatment Failure
PatientPatient: Non-adherence, poor access, intolerability, : Non-adherence, poor access, intolerability, advanced immunosuppression (low CD4 counts)advanced immunosuppression (low CD4 counts)
DrugsDrugs: Low potency, poor absorption, drug : Low potency, poor absorption, drug interactions, toxicities, complex dosing regimensinteractions, toxicities, complex dosing regimens
HIV strainsHIV strains: High viral load, transmitted (pre-: High viral load, transmitted (pre-existing) resistanceexisting) resistance
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Principles of Antiretroviral Therapy
If failure is detected as increasing viral load If failure is detected as increasing viral load
(HIV levels in blood) (HIV levels in blood)
– Measure a second blood sample for viral load Measure a second blood sample for viral load to confirm - ? error or brief “blip”to confirm - ? error or brief “blip”
– Question patient about adherence toxicity, Question patient about adherence toxicity, and other drugs, and other drugs,
– If applicable, provide adherence counseling If applicable, provide adherence counseling and /or change to new drugsand /or change to new drugs
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Adherence Newer name for “compliance” to various components of medical Newer name for “compliance” to various components of medical
care:care:– Attending clinicAttending clinic– Filling prescriptionsFilling prescriptions– Taking medications as prescribedTaking medications as prescribed– Reporting new symptoms accurately and quickly to providersReporting new symptoms accurately and quickly to providers
Poor compliance with anti retroviral drugs can have serious, Poor compliance with anti retroviral drugs can have serious,
irreversible consequences (resistance or toxicity)irreversible consequences (resistance or toxicity)
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Impact of Self-Reported AdherenceImpact of Self-Reported Adherence on HIV Suppression in Failing Patientson HIV Suppression in Failing Patients
Impact of Self-Reported AdherenceImpact of Self-Reported Adherence on HIV Suppression in Failing Patientson HIV Suppression in Failing Patients
0
10
20
30
40
50
<80% 80-95% 95-99% 100%
Pe
rce
nt
of
pa
tie
nts
P
erc
en
t o
f p
ati
en
ts
su
pp
res
se
ds
up
pre
ss
ed
N = 112
Self-reported Percentage of ARV medication takenSelf-reported Percentage of ARV medication taken
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Common Reasons for Non-Adherence in US Patients
57
39
22 20
0
10
20
30
40
50
60
Forgot Side Effects Felt Well Suspect NotWorking
Per
cent
of P
atie
nts
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Quarter-Year of Diagnosis / Death
HAART Decreased AIDS and Deaths of Adults in USA
0
5,000
10,000
15,000
20,000
25,000
1985 19861987 1988 1989 1990 1991 1992 19931994 199519961997 1998 1999
DeathsAIDS
Nu
mb
er
of
Case
s /
Death
s
HAARTCombo Rx
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Russians at Summer School for HIV Volunteers
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History of the AIDS Epidemic
– Initial definitions of a new disease 25 years ago• Case series of unusual opportunistic tumors and infections
(Kaposi’s Sarcoma, PCP, HSV) in gay men in the United States (1981).
– Expanded recognition (1982-88) of:• Risk groups including transfusion recipients (including
hemophiliacs), IV drug users, Haitians, and heterosexual Africans seeking treatment in Europe (1982-84).
• Clinical manifestations in new organs (eg, brain, gut, heart, kidney, and endocrine glands)
• New opportunistic infections (eg, cryptococcal meningitis) were identified
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History of the AIDS Epidemic
– Retroviral cause of AIDS (HIV) discovered in 3 laboratories (Montagnier, Gallo, and Levi, 1985)
– Diagnostic methods devised to assess HIV infection by detecting antibodies and levels of immunosuppression
• ELISA and immunoblotting for HIV infection developed soon after HIV was isolated (1986)
• Criteria for case definitions for AIDS, opportunistic infections (OIs), organ-specific syndromes (e.g., dementia), and acute HIV infections followed (1987-88)
• CD4 lymphocyte depletion noted initially (1981) were found to predict risk of progression to OIs and death
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History of the AIDS Epidemic– Anti-OI and Anti-retroviral therapy
• Treatment and prophylaxis of opportunistic infections (eg, PCP, MAC, and CMV) (1983-90)
• Antiretroviral drugs of several classes - [1987 (AZT), 1996 (Protease Inhibitors (= PI) and NNRTI), presently 21 agents approved
• Perinatal prophylaxis to prevent maternal-child transmission (1992)
• Assays for HIV in blood improve management of ARV drugs by providing feedback of their effects (1996)
• Delayed treatment strategy adopted because: – Safety demonstrated for patients with high CD4 counts – Metabolic complications of long term ARV therapy
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Faces of HIV/AIDS HIV-infected Activist from Chad
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Future of the HIV Epidemic
Major current and future interventions against HIVMajor current and future interventions against HIV– behavioral preventionbehavioral prevention - both a sociopolitical and - both a sociopolitical and
technical (social marketing) problemtechnical (social marketing) problem– treatmenttreatment - a complex, but soluble problem, with - a complex, but soluble problem, with
current medications dependent on massive aid and current medications dependent on massive aid and technical assistancetechnical assistance
– vaccinesvaccines - a technical problem, not likely to be - a technical problem, not likely to be available soonavailable soon
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Principles of Responding to the HIV Eidemic
Test Test - increase voluntary testing in health care settings and tie to - increase voluntary testing in health care settings and tie to
accessible treatment, start with interruption of maternal transmission to accessible treatment, start with interruption of maternal transmission to
neonates with simple, short oral regimensneonates with simple, short oral regimens
TreatTreat - provide drugs and support medical and public health - provide drugs and support medical and public health
infrastructure for treating HIV ,TB, and related diseases, using donations infrastructure for treating HIV ,TB, and related diseases, using donations
from developed world and beginning in Africa from developed world and beginning in Africa
PreventPrevent - focus on infected persons as vectors and drugs to prevent - focus on infected persons as vectors and drugs to prevent
maternal-child transmissionmaternal-child transmission
Count Count - build surveillance and research into delivery of all the above - build surveillance and research into delivery of all the above
interventions to assess and improve each componentinterventions to assess and improve each component
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Current Responses to the Global HIV Epidemic
Total support of anti-HIV activity has increased rapidly over past Total support of anti-HIV activity has increased rapidly over past
5 years thru aid from USG and UN Global Fund5 years thru aid from USG and UN Global Fund– Initial aid was targeted only to HIV preventionInitial aid was targeted only to HIV prevention– HIV treatment now supported as prices of generic drugs made HIV treatment now supported as prices of generic drugs made
in India and Brazil have dropped (350-500 US$/year)in India and Brazil have dropped (350-500 US$/year)– Tuberculosis, the major complication of HIV in Africans, is Tuberculosis, the major complication of HIV in Africans, is
being simultaneously addressedbeing simultaneously addressed– Some countries such as Thailand, Uganda and Botswana have Some countries such as Thailand, Uganda and Botswana have
reduced rates of new HIV infections thru public education, but reduced rates of new HIV infections thru public education, but many other countries have responded inadequatelymany other countries have responded inadequately
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Responding to AIDS In the Underdeveloped World
Major problems in the developing nations – Poorly educated populations without experience or
skills in using medications for chronic diseases– Denial of seriousness and implications of epidemic – Political instability, war, and corruption – Poverty - limitations of infrastructure and trained
personnel for delivery of a massive program of health care, especially in rural areas
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Responding to AIDS In the Underdeveloped World (Jeffery Sachs, Director, Center for International Development,
Columbia, Univ.)
Potential Solutions– Limit goals
• Treat only symptomatic patients with – diarrhea/wasting, – opportunistic infections, – neurological disease, or– low CD4 counts (<200)
• Minimize the variety of drugs offered • Minimize monitoring for toxicity• Don’t insist on“fairness” of access ( eg “ if you can’t treat all,
treat no one” may be contra-productive)
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Responding to AIDS In the Underdeveloped World
Evolving Solutions– Reduce drug costs through
• Challenge or ignore patents on antiretroviral drugs• Manufacture drugs locally or import from countries with
reduced labor costs• Maintain high prices in developed countries to maintain
incentives for pharmaceutical companies to continue drug development, distribution, and low costs in poor countries
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Responding to AIDS In the Underdeveloped World
Evolving Solutions– Demonstration Projects have shown that
• Relatively inexpensive, low tech methods for diagnosis of HIV from blood or saliva are accurate
• Delivering ARV is feasible in small pilot programs in many countries
• Directly-observed, once-daily regimens work• Intense monitoring for toxicity and effectiveness is not
absolutely necessary
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Responding to AIDS In the Underdeveloped World
Research agendas– Demonstration Projects are needed to investigate
• How can stigmatization and discrimination be reduced to encourage testing, eg, will availability of treatment increase persons at risk to seek testing?
• What level of medical monitoring of ARV therapy is cost effective?
• Are short term benefits of ARV are lost from selection and transmission of drug resistant HIV?
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Responding to AIDS In the Underdeveloped World
Effects of treating
– Motivates infected persons to seek testing
– Decreases new infections by decreasing HIV in genital secretions
– Conserves human capital for economic development
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Faces of HIV/AIDSHIV-infected Couple, India
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Why Be Hopeful?
Prevention is working – prevalence is stabilizing or falling in
many countres in sub-Saharan Africa
Technical progress has reduced costs of therapy– Costs of testing for HIV are low (<$10 / test )– Costs of generic drugs is $300- 500 / person / year – Therapy can be delivered by DOT and monitored for as little
as $450 / person / year
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Why Be Hopeful?
Political Progress– Presidents Emergency Program For AIDS Relief (PEPFAR)
• President Bush pledged $15 B for directly funding ARVs in 12 African and 2 Caribbean countries most impacted by HIV
• AIDS epidemic is seen a sociopolitical problem and a priority for US foreign policy spending
– UN Global Fund has begun to organize responses in and distribute funding to developing countries
– Many developing countries have begun to to acknowledge and address their epidemics
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Why Worry?
Problems with Presidents Emergency Program For AIDS
Relief (PEPFAR)– Unilateralism - Global Fund separate from US program– Corruption – Misdirection of funds in multiple
countries (eg, Uganda)– Disease-specific focus – other diseases (malaria) and
critical nutritional, public health, and economic needs not integrated or neglected
– Limited geographical coverage - focused on only 18 affected countries
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Why Worry?
Consequences of Failure to Implement Consequences of Failure to Implement
PEPFAR Effectively PEPFAR Effectively
– Millions of lives lost and diminishedMillions of lives lost and diminished
– Socioeconomic development of Africa and Socioeconomic development of Africa and Asia delayedAsia delayed
– Future “medical foreign aid “ stigmatizedFuture “medical foreign aid “ stigmatized
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Information sources
UNAIDS web site (www.unaids.org)UNAIDS web site (www.unaids.org)
Centers for Disease Control wEB site (www.cdc.gov)Centers for Disease Control wEB site (www.cdc.gov)
UCSD AIDS Research Institute web site UCSD AIDS Research Institute web site
(hsrd.ucsd.edu/cfar/admin.html)(hsrd.ucsd.edu/cfar/admin.html)