HIV / AIDS – 2006 An Overview for International Volunteers Allen McCutchan, MD, MSc Professor Of Medicine UCSD

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

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

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

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

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

Evolutionary Relationships of Evolutionary Relationships of Primate Retroviruses Related to HIVPrimate Retroviruses Related to HIV

HIV -1 N

SIV = simian (primate) HIV = human

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

Distribution of HIV-1 Cladesin Sub-Saharan Africa

Faces of HIV / AIDS Russian Mother and Daughter

Scanning Electron Micrograph and Cartoon of the Structure of an HIV

Virion

External envelop proteins

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

Budding of HIV from CD4 Cell

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

Cytograph in Ethiopian Army Hospital Laboratory


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


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

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

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

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

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

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

PATHOGENISIS OF HIV INFECTION:No Progression With Low Level Viremia

CD4

RNA

Primary HIV Chronic Non-progressive HIV Infection

RNA Set Point ~ 103

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

PATHOGENISIS OF HIV INFECTION:Rapid Progression With High Level Viremia

RNA

CD4

32

Primary HIV AIDS

Years

RNA Set Point ~ 106

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


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))


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)

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

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)

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)

Current treatment options: Non Nucleosides (NNRTIs)

• Nevirapine (Viramune)Nevirapine (Viramune)• Efavirenz (Sustiva)Efavirenz (Sustiva)• Delavirdine (Rescriptor)Delavirdine (Rescriptor)

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)

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


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)


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

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


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

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)

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

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

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

Russians at Summer School for HIV Volunteers

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

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

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

Faces of HIV/AIDS HIV-infected Activist from Chad

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

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

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

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

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)


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


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


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?


Effects of treating

– Motivates infected persons to seek testing

– Decreases new infections by decreasing HIV in genital secretions

– Conserves human capital for economic development

Faces of HIV/AIDSHIV-infected Couple, India

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

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

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

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

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)

Documents

HIV / AIDS – 2006 An Overview for International Volunteers Allen McCutchan, MD, MSc Professor Of Medicine UCSD