Potential new class of AR & AIDS treatment

[terpie82]

Wen Z, et al. Drug Metab Dispos. 2006 Jun 2; [Epub ahead of print]
U. North Carolina at Chapel Hill.
PA-457 [3-O-(3’,3’-dimethylsuccinyl)-betulinic acid], a betulinic acid derivative containing double carboxylic acid groups (Fig. 1), is the first in a new class of anti-retrovirals termed maturation inhibitors that disrupt viral maturation, the last step in the virus life-cycle. PA-457 specifically inhibits processing of the HIV-1 capsid precursor, capsid-SP1, thereby preventing normal viral core condensation (Li et al., 2003). Preclinical studies have shown that PA-457 retains full activity against viral strains resistant to currently available treatments, and is effective in an animal model of HIV infection. Recently, PA-457 has demonstrated positive results in a phase I/II clinical trial in HIV-infected patients.

Walensky RP, et al. J Infect Dis. 2006 Jul 1;194(1):11-9. Epub 2006 Jun 1.
Divisions of Infectious Disease and General Medicine, Department of Medicine, Massachusetts General Hospital, and Division of Infectious Diseases, Brigham and Women's Hospital, Boston, USA
Background. As widespread adoption of potent combination antiretroviral therapy (ART) reaches its tenth year, our objective was to quantify the cumulative survival benefits of acquired immunodeficiency syndrome (AIDS) care in the United States.Methods. We defined eras corresponding to advances in standards of human immunodeficiency virus (HIV) disease care, including opportunistic infection prophylaxis, treatment with ART, and the prevention of mother-to-child transmission (pMTCT) of HIV. Per-person survival benefits for each era were determined using a mathematical simulation model. Published estimates provided the number of adult patients with new diagnoses of AIDS who were receiving care in the United States from 1989 to 2003.Results. Compared with survival associated with untreated HIV disease, per-person survival increased 0.26 years with Pneumocystis jiroveci pneumonia prophylaxis alone. Four eras of increasingly effective ART in addition to prophylaxis resulted in per-person survival increases of 7.81, 11.05, 11.57, and 13.33 years, compared with the absence of treatment. Treatment for patients with AIDS in care in the United States since 1989 yielded a total survival benefit of 2.8 million years. pMTCT averted nearly 2900 infant infections, equivalent to 137,000 additional years of survival benefit.Conclusions. At least 3.0 million years of life have been saved in the United States as a direct result of care of patients with AIDS, highlighting the significant advances made in HIV disease treatment.

[Oceanbeach]

This looks like it is good news but, I am only an average guy and do not understand most of what is written.  Our friend and forum member Blondbeauty often translates Spanish to English so everyone can understand the articles he finds.  Can this article be put in laymans terms?  Have the best day
Michael

www.Commission-on-AIDS.org

[terpie82]

Hi SB,
The first article reports on a potential new class of anti-retrovirals, maturation inhibitors which prevents proper assembly of the capsid proteins found on the surface of the virus. Without the capsids, the virus is rendered useless and cannot affect other cells.

To see the capsids and get more info:
http://images.google.com/imgres?imgurl=http://www.massey.ac.nz/~wwbioch/Prot/protover/hiv.gif&imgrefurl=http://www.massey.ac.nz/~wwbioch/Prot/protover/protext.htm&h=308&w=300&sz=37&tbnid=mGRXr5o-JLByRM:&tbnh=112&tbnw=109&hl=en&start=2&prev=/images%3Fq%3Dcapsid%2Bprotein%2BHIV%2B%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN
or the oval balloons on the surface of the virus:


To see a list and short summary of other potential inhibitors:
http://www.aidsmap.com/en/docs/1DADAB42-752E-4894-B0DF-91DFA3A38CC0.asp

The second article reports on the effectiveness of treatment in the US such as the survival increase of 13 years/per person infected since 1989 (compared to no treatment) and 3 million years of life saved in the US.

[Oceanbeach]

Thank you ever so much.  Have the best day
Michael

www.Commission-on-AIDS.org

[HIVworker]

To add to that explanation. The viral core contains the blueprint of the virus - which is injected into cells. The blueprints end up in the nucleus and are permanently inserted into the host DNA by integrase. Surrounding the blue-prints is the viral core - made predominantly of a protein called capsid. Capsid assembles into a cone-shape during maturation of the virus..the thing in the middle of Terpie's picture.

The cone shaped core is the thing that is injected into the cell and then undergoes an ordered disassembly process called uncoating.

Ucoating then starts the process of reverse transcription that prepares the blueprints for insertion into the chromosomes.

Without this ordered disassembly process, the virus can not correctly initiate the reverse transcription nor copy it's blueprints into a form that can be inserted into the host DNA. Therefore, the virus is useless. Protease inhibitors also inhibit this maturation process but in a different and more global manner. Basically the virus is defunct when it gets made and infection with such viruses is a dead-end.

R