University of Miami HIV vaccine

[freewillie99]

University of Miami researcher's HIV vaccine latest lift in fight vs. AIDS

A Miami researcher says she is well along in the development of a vaccine to help those already infected with HIV

As an HIV vaccine breakthrough in Thailand stirs interest and hope, a pioneering AIDS researcher at the University of Miami Medical School says she is preparing to start human trials for a new vaccine that would fight the deadly virus.

While the Thai experiment is the first to prevent infection by the HIV virus that creates AIDS, Dr. Margaret Fischl of UM is working on a vaccine that would be given to patients already infected with HIV to help boost their immune systems to fight off the disease. Both vaccines are years away.

If successful, the Fischl vaccine could replace the two- and three-drug ``cocktails'' of antiretroviral drugs now used to improve and prolong the lives of people with HIV. That approach is expensive and also produces numerous side effects.

Fischl is one of the world's most respected AIDS researchers. In 1987, she was instrumental in developing AZT, a breakthrough that provided the first effective antiviral medicine that stopped AIDS from killing nearly all of its victims. It is still in use today along with many newer drugs, and AIDS deaths have plummetted.

Her new vaccine, being developed in conjunction with a major out-of-state biotech firm, has been successful in treating HIV in small mammals up to the size of rhesus monkeys. It should be ready for human trials by about January, she said.

``The goal is to use the vaccine as the mainstay of treatment, so infected people would no longer need HAART (highly active antiretroviral therapy), with its expense and side effects,'' Fischl said. ``With this, they would take a shot every year to boost their systems and keep them in shape.''

ENCOURAGING NEWS

Alan Bernstein, executive director of the New York-based Global HIV Vaccine Enterprise, which is not involved in Fischl's study, called news of Fischl's vaccine trial ``great news for people who already have HIV.''

``Obviously, the vaccine in the Thai trial would not help people who already have HIV'' because it's given to uninfected people to prevent HIV, he said. ``So this vaccine would be very complementary.''

Also, he said, people who control HIV with antiretroviral drugs are never cured and must stay on the drugs for life. And he said new research suggests that such people are developing signs of premature aging, such as arthritis and early dementia.

Since a therapeutic vaccine would be aimed more directly at the HIV virus, it might have fewer toxic side effects, he said. It, too, would not be a cure.

Fischl and the biotech firm, which she cannot yet name, have been working on the new vaccine for years. She said more details will be released soon. It has been successful ``in vitro'' in the lab and has worked well in trials with six rhesus monkeys who had been infected with the HIV virus, she said.

``We know the vaccine works all the way up to the monkey model. We know its safety profile already,'' Fischl said. By about January, she said, it should be ready for its first trials in humans. About 30 volunteers would be recruited at several universities.

TREATING HUMANS

Human trials are very sensitive, she said.

``I feel very strongly that when you do a study in humans, even if you have volunteers lined up around the block, you move slowly. You give a dose to the first patient, and you wait to make sure there are no side effects. Then you give it to the second patient.''

Eventually, the vaccine would be given to humans with HIV who then would go off their antiretroviral medicines. They would be watched carefully to see if any had ``breakthroughs'' of the HIV virus.

If all goes well, the new vaccine could seek ``fast-track'' approval by the FDA and be on the market in three years, she said.

Fischl praised the breakthrough in Thailand. She said she favors bringing it to U.S. markets, even though it protected only 31 percent of Thai subjects who took it.

``It this were a flu vaccine, it would be stopped cold because the success rate is so low,'' she said. Vaccines against H1N1 swine flu and regular seasonal flu report success at more than 85 percent.

In the Thai trials, new HIV infections occurred in 51 of the 8,197 given the vaccine and in 74 of the 8,198 who received dummy shots -- a 31 percent reduction in the number of new infections.

It's not a very big difference, Fischl said, ``but you could argue that since this epidemic is moving so quickly, you might want to bring it to market. I guess anything at this point that can stop the spread of HIV is important.''

The Thai vaccine was tested against local strains of HIV, leading some scientists to wonder if it would work against U.S. strains of HIV. But Fischl said U.S. strains are similar enough that that should not be an issue.

Around the world, at least 15 AIDS vaccine trials are under way at various stages, with more than 8,500 volunteer subjects in the United States, Brazil, South Africa, Thailand and Peru, according to the HIV Vaccine Trials Network, which tracks HIV vaccine research. Drug companies involved include Merck, Wyeth, Chiron/NOVAD, Therion, GeoVax and others. Two previous trials in Thailand were failures.

DISEASE HOT SPOTS

In the United States, HIV/AIDS has gone from a lethal epidemic to a chronic disease. New HIV infections peaked in the mid-1980s at about 130,000 cases per year, declined quickly in 1995 when antiretroviral drugs came on the market, and have plateaued at about 55,000 new cases per year, according to the U.S. Centers for Disease Control and Prevention.

South Florida is especially hard hit. In Miami-Dade in 2008, one in every 82 Hispanic men, one in every 60 white non-Hispanic men and one in every 29 African-American men are living with HIV, the Florida Department of Health says.

In Broward, those living with HIV include one in 98 Hispanic men, one in 76 non-Hispanic white men and one in every 42 African-American men.

At the end of 2007, more than 500,000 persons in the 34 states that report such statistics were living with HIV/AIDS.

Worldwide, about 33 million were living with HIV/AIDS, with 2.7 million new infections that year, the World Health Organization says.

[veritas]

Free,

They are certainly keeping this one close to the vest ! I haven't been able to find anything on it.
Maybe I'm looking in all the wrong places. If anyone can find any additional info please post!

v

[freewillie99]

All I've seen is that single article.  Here's a link, but it's what's posted above:

http://miamiherald.typepad.com/gaysouthflorida/2009/09/um-researcher-dr-margaret-fischl-preparing-vaccination-to-fight-hiv.html

[marius68]

I hope Dr. Fischl  is  up for something  but from her publications since 2000 I can't see any work related to a new therapeutical vaccine. I'm including the list of references below and I believe it's fairly complete. Also couldn't find any patents. It seems this work is more secretive than the Manhattan project!!

List of papers of Dr. M. Fischl:
1.   Sereti, I., et al., IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood, 2009. 113(25): p. 6304-6314.
2.   Hammer, S.M., et al., Antiretroviral treatment of adult HIV infection - 2008 recommendations of the International AIDS Society USA panel. Jama-Journal of the American Medical Association, 2008. 300(5): p. 555-570.
3.   Tebas, P., et al., Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels - Results of a prospective randomized trial (AIDS clinical trial group 5725s). Jaids-Journal of Acquired Immune Deficiency Syndromes, 2007. 45(2): p. 193-200.
4.   Slish, J., et al., Assessing the impact of substance use and hepatitis coinfection on atazanavir and lopinavir trough concentrations in HIV-infected patients during therapeutic drug monitoring. Therapeutic Drug Monitoring, 2007. 29(5): p. 560-565.
5.   Moore, J.D., et al., Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy. Antiviral Therapy, 2007. 12(6): p. 981-986.
6.   Ma, Q., et al., Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. Pharmacogenomics, 2007. 8(3): p. 227-235.
7.   King, W.D., et al., Attitudes and perceptions of AIDS clinical trials group site coordinators on HIV clinical trial recruitment and retention: A descriptive study. Aids Patient Care and Stds, 2007. 21: p. 551-563.
8.   Keil, K., et al., Integration of atazanavir into an existing liquid chromatography UV method for protease inhibitors: Validation and application. Therapeutic Drug Monitoring, 2007. 29(1): p. 103-109.
9.   Higgins, N., et al., Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir. American Journal on Addictions, 2007. 16(6): p. 488-494.
10.   Fischl, M.A., et al., Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen. Aids, 2007. 21(3): p. 325-333.
11.   DiFrancesco, R., et al., Buprenorphine assay and plasma concentration monitoring in HIV-infected substance users. Journal of Pharmaceutical and Biomedical Analysis, 2007. 44(1): p. 188-195.
12.   Krown, S.E., et al., Interferon-alpha 2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma - An AIDS malignancy consortium phase I trial. Jaids-Journal of Acquired Immune Deficiency Syndromes, 2006. 41(2): p. 149-153.
13.   Kilby, J.M., et al., A randomized, partially blinded phase 2 trial of antiretroviral therapy, HIV-specific immunizations, and interleukin-2 cycles to promote efficient control of viral replication (ACTG A5024). Journal of Infectious Diseases, 2006. 194(12): p. 1672-1676.
14.   Hammer, S.M., et al., Treatment for adult HIV infection - 2006 recommendations of the International AIDS Society-USA panel. Jama-Journal of the American Medical Association, 2006. 296(7): p. 827-843.
15.   Smith, P.F., et al., Pharmacokinetics of nelfinavir and efavirenz in antiretroviral-naive, human immunodeficiency virus-infected subjects when administered alone or in combination with nucleoside analog reverse transcriptase inhibitors. Antimicrobial Agents and Chemotherapy, 2005. 49: p. 3558-3561.
16.   Smith, P.F., et al., Population pharmacokinetics of delavirdine and N-delavirdine in HIV-infected individuals. Clinical Pharmacokinetics, 2005. 44(1): p. 99-109.
17.   Yeni, P.G., et al., Treatment for adult HIV infection - 2004 recommendations of the International AIDS Society-USA panel. Jama-Journal of the American Medical Association, 2004. 292(2): p. 251-265.
18.   DiCenzo, R., et al., Pharmacokinetics of indinavir and nelfinavir in treatment-naive, human immunodeficiency virus-infected subjects. Antimicrobial Agents and Chemotherapy, 2004. 48(3) p. 918-923.
19.   Robbins, G.K., et al., Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. New England Journal of Medicine, 2003. 349(24) p. 2293-2303.
20.   Morse, G.D., et al., Effect of food on the steady-state pharmacokinetics of delavirdine in patients with HIV infection. Clinical Drug Investigation, 2003. 23(4) p. 255-261.
21.   Hirsch, M.S., et al., Long-term efficacy, safety, and tolerability of indinavir-based therapy in protease inhibitor-naive adults with advanced HIV infection. Clinical Infectious Diseases, 2003. 37 p. 1119-1124.
22.   Hammer, S.M., et al., A randomized trial of nelfinavir and abacavir in combination with efavirenz and adefovir dipivoxil in HIV-1-infected persons with virological failure receiving indinavir. Antiviral Therapy, 2003. 8(6): p. 507-518.
23.   DiCenzo, R., et al., Indinavir, efavirenz, and abacavir pharmacokinetics in human immunodeficiency virus-infected subjects. Antimicrobial Agents and Chemotherapy, 2003. 47(6): p. 1929-1935.
24.   Daikos, G.L., et al., Multidrug-resistant tuberculous meningitis in patients with AIDS. International Journal of Tuberculosis and Lung Disease, 2003. 7(4): p. 394-398.
25.   Young, B., et al., Open-label study of a twice-daily indinavir 800-mg/ritonavir 100-mg regimen in protease inhibitor-naive HIV-infected adults. Jaids-Journal of Acquired Immune Deficiency Syndromes, 2002. 31(5): p. 478-482.
26.   Yeni, P.G., et al., Antiretroviral treatment for adult HIV infection in 2002 - Updated recommendations of the international AIDS Society-USA panel. Jama-Journal of the American Medical Association, 2002. 288(2): p. 222-235.
27.   Demeter, L.M., et al., Detection of replication-competent human immunodeficiency virus type 1 (HIV-1) in cultures from patients with levels of HIV-1 RNA in plasma suppressed to less than 500 or 50 copies per milliliter. Journal of Clinical Microbiology, 2002. 40(6): p. 2089-2094.
28.   Demeter, L.M., et al., Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine - AIDS clinical trials group protocol 320. Annals of Internal Medicine, 2001. 135(11): p. 954-964.
29.   Arduino, J.M., et al., Do HIV type 1 RNA levels provide additional prognostic value to CD4(+) T lymphocyte counts in patients with advanced HIV type 1 infection? Aids Research and Human Retroviruses, 2001. 17(12): p. 1099-1105.
30.   Morse, G.D., et al., Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. Antiviral Research, 2000. 45(1): p. 47-58.
31.   Goodgame, J.C., et al., Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. Antiviral Therapy, 2000. 5(3): p. 215-225.
32.   Fletcher, C.V., et al., Competing drug-drug interactions among multidrug antiretroviral regimens used in the treatment of HIV-infected subjects: ACTG 884. Aids, 2000. 14(16): p. 2495-2501.
33.   Demeter, L.M., et al., Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260). Antimicrobial Agents and Chemotherapy, 2000. 44(3): p. 794-797.
34.   Carpenter, C.C.J., et al., Antiretroviral therapy in adults - Updated recommendations of the International AIDS Society-USA Panel. Jama-Journal of the American Medical Association, 2000. 283(3): p. 381-390.
35.   Babiker, A., et al., Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: A meta-analysis. Aids Research and Human Retroviruses, 2000. 16(12): p. 1123-1133.

[NYCguy]

Interesting...this is certainly the first I've heard of this.  And no mention of the technology, proteins it targets, ect.  And of note - no mention of the 'major out-of-state biotech firm" that she is partnering with.  There must be some way to figure this out.  I wonder if it is similar to Geovax?