1. HIV Vaccine Development
Issues related to Goals:
Prevention vs. Treatment
Neutralizing antibodies vs. cell-based (CD4/CD8)
Mucosal vs. Intravenous immunity
Issues related to Means:
Protein(s) - which one(s) and how presented
Whole virus - attenuated* / killed
*trials appear to have led to HIV infection
Vectors - viral, DNA
Prime and Boost

2. Vaccines in Clinical Trials
Treatment Trials
REMUNE: gp120-depleted killed whole
HIV-1 virus
Phase III in US - was disappointing,
Focused on HAART patients with
low/undetectable HIV-1 RNA
Increased CD4+ counts, some decreased
HIV-1 RNA, but not as promising as hoped
Sponsor company Immune Response underwent
Restructuring. Now focusing on:
REMUNE for treatment naive pateints (potential to
delay need for HAART)
IR103 = REMUNE + adjuvant, is in Phase I

3. Vaccines in Clinical Trials
AIDSVAX - gp120-based vaccine for prevention
originally co-sponsored by NIH, since pulled
support due to lack cell-based response.
Phase III clinical trial showed no effect in
patient population as a whole; however,
certain minority groups showed a modest
effect - not statistically/biologically
relevant
Sponsor Company VaxGen is being sued by
investors for not being up-front
with preliminary clinical trial data

4. Vaccines in Clinical Trials
Aventis: ALVAC vCP-1452
canarypox vector expressing
HIV-1 env-gag-pol
Currently undergoing a controversial
Phase III trial in combination with
AIDSVAX B/C in Thailand
Merck: Ad5
adenovirus vector expressing gag
Problems with patients already exposed to Ad5

5. Vaccines in Clinical Trials
Epimmune: EP HIV-1090
DNA-based vaccine includes 21 key elements
HIV-1 epitopes plus a Universal
Helper T-cell epitope (to enhance
magnitude and duration of response)
Phase I trials ongoing - so far the vaccine
is well tolerated, but immune responses
are low - modified dosing route and
schedule are in the works.

6. Opportunistic Viral Infections
Cytomegalovirus (CMV) - widespread virus, up to 85%
of total US population infected with no symptoms.
In AIDS patients, can cause liver/lung damage
and is a leading cause of blindness
Recently Approved:
- Vistide (cidofovir)
- Vitravene (fomivirsen)*
- Foscavir (foscarnet)
- Cytovene (gangcylovir)
Herpes Simplex Virus (HSV)
-Valacyclovir (Valtrex)

7. How Antisense Drugs work
protein
mRNA
DNA
antisense drug
mRNA destroyed

8. Opportunistic Infections
Pneumocystis carinii pneumonia (PCP)
65% of AIDS patients develop pulmonary infection
mortality rate is 10-50% per episode
Recently Approved:
- Bactrim
- Septra
- NebuPant (pentamidine)
- Pentam (pentamidine)
- Neutrexin (trimetrexate)
- Mepron (atovaquinone)
In Trials:
- dapsone

9. Opportunistic Mycobacterial Infections
Tuberculosis-
Recently Approved:
-Rifapentine
Mycobacterium avium- intracellulare complex (MAC)
- Zithromax (azithromycin)
- Mycobutin (rifabutin)
- Biaxin (clarithromycin)

10. Kaposi Sarcoma (KS)
Recently Approved:
- DaunoXome
- Doxil
- Intron A (interferon alpha-2b)
- Roferon (interferon alpha 2a)
- Taxol
- Panretin (alitretinoin)
In Trials:
- Thalidomide
- Virulizin