26 YEARS OF HIV EPIDEMY 10 years HAART

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26 YEARS OF HIV EPIDEMY10 years HAART
Dan Turner, MD, Tel-Aviv Sourasky Medical Center
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Case Presentation

• Male 41 years old
• Weight lost
• Cough
• Blurred vision
• Weakness right arm and leg
• HIV Serology
• What next?

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AIDS-HIV

• HIV Human Immunodeficiency
• Virus
• AIDS Acquired Immuno-Deficiency Syndrome

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HIV in Israel 1980- June 20044141 new cases
1 new patient every day
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Transmission of HIV
Sexual Route Homo-Heterosexual
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HIV in Israel Exposure Categories (until end
2005)
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World Distribution of different Subtypes
A
A
A,C
G
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Natural History CD4 and VL and clinical events
Acute HIV
Symptomatic
Asymptomatic Phase
weeks
Years
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Acute Retroviral Syndrome
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Symptoms in HIV
According toCD4
According to system
CD4gt500 mucocutaneous candida 200-500
Pneumococcal pneumonia tuberculosis herpes
zoster cervical neoplasia Kaposis sarcoma NHL
100-200 PCP AIDS dementia Wasting 50-100
toxoplasmosis cryptococcosis lt50 CMV
retinitis MAC cryptosporidiosis PML primary CNS
lymphoma
Cryptococal meningitis
Toxoplasmosis primary CNS lymphoma PML
All systems tuberculosis MAC cytomegalovirus NHL K
aposis sarcoma
CMV retinitis
Candida esophagitis
PCP
Cryptosporidium
carcinoma cervix, anal
CMV- Cytomegalovirus, CNS- Central Nervous
System, MAC- Mycobacterium avium NHL-Non Hodgkin
Lymphoma, PCP- Pneumocystis carinii Pneumonia,
PML- Progressive Multifocal Leucoencephalopathy
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Oral thrush
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Hairy Leukoplakia
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Kaposi Sarcoma
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PCP
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CMV
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Cerebral Toxoplasmosis

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Progressive Multifocal Leuco-encephalopathy
(PML)
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Prophylaxis

• PPDgt 5mm TB (INH)
• CD4 lt 200 PCP (TMP/SMX)
• CD4lt 50 MAC (Azyhtro/Clarythro)

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Antiretroviral Therapy
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Treatment History

• 1981 HIV discovery
• 1987 AZT
• 1990 DDI and TMP/SMX prophylaxis for PCP and
  toxoplasmosis
• 1994AZT to prevent maternofetal transmission
• 1996 HAART- Highly Active Antiretroviral Therapy
• 2000 Viral Resistance
• 2003 Fusion inhibitor (T-20)
• 2006 Integrase inhibitors

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Anti HIV Drugs
HIV
RNaseH
DNA
RT RTI
T-helper(CD4)
RNA
integrase
Entry inhibitors
RNA messeger
Viral RNA
Assembly
Protease PI
Viral proteins
HIV- Human Immunodeficiency Virus, RT- Reverse
transcriptase
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Combination Therapy-1996Decrease mortality in
USA
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Decrease incidence of opportunistic infection
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Decrease in Morbidity since HAART (EuroSida)
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Nucleos(t)ides Reverse Transcriptase
InhibitorsMITOCHONDRIAL TOX

• DRUG
• AZT
• DDI
• DDC
• D4T
• 3TC
• ABACAVIR
• TENOFOVIR

• SIDE EFFECT
• BONE MARROW
• PANCREATITIS
• PNP, STOMATITIS
• PNP
• PNP
• HYPER SESITIVITY SYNDROME
• RENAL (RARE)

Peripheral Neuropathy
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Non Nucleosides Reverse Transcriptase Inhibitors

• DRUG
• EFAVIRENZ
• NEVIRAPINE
• DELAVIRDINE

• SIDE EFFECT
• NEUROLOGIC
• RASH, LIVER
• RASH

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PROTEASE INHIBITORSLipid abnormality

• DRUG
• SAQUINAVIR
• INDINAVIR
• RITONAVIR (Rtv)
• NELFINAVIR
• fosAMPRENAVIR
• Rtv/LOPINAVIR
• ATAZANAVIR
• No lipid abnormality

• SIDE EFFECT
• GI
• KIDNEY STONES
• GI
• GI
• RASH
• GI
• hyperbilirubinemia

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OTHERS

• IL2
• VACCINE
• INTEGRASE

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New drugs
Different mutational profile PI- TMC 114
(Darunavir) (FDAEC approved) NNRTI- TMC 125
New Targets

• Fusion inhibitors T-20 (Fuzeon)
• Entry inhibitors CCR5 inhibitor
• Integrase inhibitor (FDA approved)

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Evolution of DHHS guidelines as to the best time
to begin antiretroviral therapy in asymptomatic
patients
2004
gt350
lt200
Any Value
gt100,000 optional
DHHS- Department of Health and Human Services
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Major problems with the Treatment
Side Effects of the Drugs
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Failure Therapy

• COMPLIANCE!!!!!!!!!!!
• DRUG INTERACTION
• VIRAL RESITANCE

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Maternal-Child Transmission
Placebo 30-50
AZT 8
lt2
No difference of congenital abnormalities from
general population
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Effect of HAART on VL and CD4
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Immune Reconstitution
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Laboratory

• ELISA- screening
• Western Blot- confirmation
• P24 Ag
• CD4
• Viral Load
• Genotyping
• Phenotyping

Diagnosis
Follow up
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