HIV/AIDS 2008 Update

HIV/AIDS 2008 Update
By:David H. Spach, MD
Clinical Director, NWAETC
Professor of Medicine
Division of Infectious Diseases
University of Washington, Seattle

* HIV Epidemiology
* HIV Rapid Testing
* 2008 DHHS ARV Therapy Guidelines
* Antiretroviral Therapy: New Information in 2008
* New Scientific Discoveries
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Epidemiology*
Question
* In August 2008, the CDC reported their use of new epidemiologic methods that has led to significant revisions in the estimates of HIV incidence in the United States.

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In this recent report, which one of the following statements is TRUE regarding HIV infections in the United States in 2006?

* The number of estimated new infections in 2006 has been revised to a lower number (now 32,000 instead of 40,000)
* The rate (per 100,000 persons) of new infections in blacks was 7x whites
* Heterosexual sex has replaced male-to-male sex as the leading transmission category for new infections
* The number of new infections in women was greater than men
* “Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56,300.”
* “... the level of new HIV infections in the United States is higher than had previously been known, in fact approximately 40% higher than early estimates…”
Kevin Fenton, MD, PhD
Centers for Disease Control & Prevention.
HIV Rapid Testing*
Rapid HIV Tests
* In the June 18, 2008 issue of the MMWR, the NY City Department of Health and the CDC reported a problem with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test.

What was the reported problem with the OraQuick rapid HIV test?
* Contamination of test kits with mold
* Kits were shipped too close to the expiration date
* Failure of external Kit Controls to validate the assay
* Increased numbers of False-Positive results with oral fluid samples

Persons NOT Infected with HIV
OraQuick Rapid ORAL HIV Test
Confirmatory HIV Test (EIA/WB)
Preliminary
Positive
EIA
WB
Reactive
Oral Fluid
Oral
Possible Revised Approach: Rapid HIV Testing
OraQuick Rapid HIV Tests
Confirmatory HIV Test (EIA & WB)
Preliminary
Positive
Reactive
Oral
Oral Fluid
EXAMPLE: Specificity of HIV Antibody Test
Persons NOT Infected with HIV (N = 15)
EXAMPLE: Specificity of HIV Antibody Test
Antibody Test Result: Persons NOT Infected with HIV
EXAMPLE: Specificity of HIV Antibody Test
HIV Antibody Testing in Low Prevalence Setting
HIV Test Specificity
HIV Antibody Testing in Low Prevalence Setting
DHHS ARV Guidelines
Initiating Antiretroviral Therapy
* As a group, make a list of at least 5 recommendations regarding initiating antiretroviral therapy that are new/different in current 2008 guidelines when compared with guidelines that existed one year ago at this time (at that time October 2006 most recent updated version).
Initiating Antiretroviral Therapy
* NEW RECOMMENDATIONS
1. New CD4 threshold (350 cells/mm3 in 2008 instead of 200)
2. New indications for starting ARV (chronic HBV, HIVAN) in 2008
3. Less impact of HIV RNA level in 2008
4. Zidovudine-lamivudine removed from preferred list in 2008
5. Abacavir-lamivudine added to preferred list in 2008
6. Do HLA-B5701 testing if considering using abacavir
Initiating Antiretroviral Therapy January 2008 DHHS Guidelines
*Initiate Antiretroviral Therapy
Consider Antiretroviral Therapy
Construct Regimen by choosing one component from Column A and one component from Column B
Recent Concerns Regarding Abacavir
Antiretroviral Therapy New Information in 2008
Host Cellular Receptors
Extracellular Space
Intracellular Space
Entry Inhibitor: Maraviroc (Selzentry)
Host Cell Membrane
CD4 Receptor
Extracellular Space
Intracellular Space
R5 HIV
Maraviroc
CXCR4
CCR5
HIV Co-Receptor Tropism Assay Monogram Biosciences Trofile Assay
HIV-1 Tropism Assay
What is the major difference in the new ENHANCED Trofile assay when compared with the older Trofile assay?

* The new assay has a lower limit of detection of minor species (<1% compared with previous lower limit of 10%)
* Results can be obtained in 7 days with the new assay
* The new assay is accurate with very low HIV RNA levels (accurate down to 100 copies/ml)
* The new assay detects CCR5 mutants resistant to Maraviroc

HIV Co-Receptor Tropism Assay Monogram Biosciences ENHANCED Trofile Assay
Tenofovir + Lamivudine + Efavirenz (n = 38)
Eligibility
- HIV-infected
- Treatment Naive
- HIV RNA > 5,000 copies/ml
- CD4 count > 100 cells/mm3
- Randomized, double-blind
Tenofovir + Lamivudine +
Raltegravir* (n = 160)
Virologic Response: Week 24
INVESTIGATIONAL
* Background
- N = 368
- ARV-naīve
- HIV RNA > 5,000 copies/ml
- Randomized, double-blind
* Regimens (all include 2 NRTIs*)
- Efavirenz: 600 mg qd
- Rilpivirine: 25 mg qd
- Rilpivirine: 75 mg qd
- Rilpivirine: 150 mg qd
New Scientific Discoveries
A Cure for HIV?
* In July 2008, our patients starting coming in asking about the news reports regarding the newly discovered cure for HIV. The report that came out in July 2008 was related to HIV gp120 (envelope).

What new therapeutic strategy was discovered?

* A CD4 coating molecule that is an inhibitor of gp120-CD4 binding
* Use of Abzymes to destroy a critical region of gp120
* A new enzyme that cause gp120 to separate from gp41
* A new particle that destroys the human co-receptor CCR5 and thus prevents gp120-CCR5 binding

HIV: Basic Structure
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gp120
gp41
Envelope
HIV: Envelope
Abzymes
- Antibodies with enzymatic activity
- Can break down thousands of virus particles per molecule of abzyme

HIV: gp120
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HIV gp120: Abzyme Interaction .........

HIV/AIDS 2008 Update: Summary

* HIV Epidemiology
* HIV Rapid Testing
* 2008 DHHS ARV Therapy Guidelines
* Antiretroviral Therapy: New Information in 2008
* New Scientific Discoveries

HIV/AIDS 2008 Update.ppt