New HIV Medication Regimen

For more information on these meds and test regulations and availability worldwide go to this link:

http://www.mcgill.ca/microimm/department/associate_adjunct_prof/wainberg/

Most doctors around the world have access to test information and access points for these meds as some of them have not been approved in the U.S. and in other parts of the world. I DO NOT know if these meds will be made available in Africa as of yet, as most of them are still in test phase. I don’t have information as to where these meds are being researched world wide, but Dr. Wainberg can help you with your inquiries. I would talk to your front line primary HIV / AIDS doctors and inquire about the new meds on the formulary and in test and research phases. NOTE: That your labs will be checked prior to being given access to new meds and they are quite strict here by lab results and acceptance parameters.

I am reposting the post here – along with my blog (The Evolution of Jeremiah) maybe some of you out there can use this information in your HIV treatment.

This Friday I will begin these new drugs when my local pharmacy receives some of my meds. These four drugs based on my Geno-Pheno typing information on my last checkup tells us that these drugs used in conjunction should produce great results as my doctor is confident that this mixture of meds will work. He attended a seminar this week about these meds and studies have been very promising.

Some of the meds, as stated below are not YET on the market, even here, but I am getting them through expanded release on governmental approval, and a selection process based on current lab work collected at the clinic site. Drugs released to patients on expanded release are closely monitored and approved based on current labs that will be checked every six weeks, once treatment has begun.

I have to drop labs once this week for baseline numbers – then repeat labs every six weeks after treatment begins.

I have already begun to loose weight now that I am off the Zerit, Videx EC and Viracept regimen that I was on. I have been on a drug vacation for a month now, as my body is starting to change. I am also on a new diet – less sugar, diet drinks and juices, and a lower cholesterol and carbohydrate meals.

Here is the drug information for those of you who might be interested.

1. TMC 125 (Etravirine) 100 mg. Twice a Day (BID)

AIDSmeds.com

What is Etravirine?

• Etravirine is in a category of HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Etravirine prevents HIV from entering the nucleus of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.
• Etravirine will need to be used in combination with other drugs. Clinical trials will evaluate its effect in combination with other drugs, including protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs).

What is already known about Etravirine?

• The etravirine dose being studied in phase III clinical trials is two 100mg tablets taken by mouth, with food, twice a day.
• Like other NNRTIs, etravirine might interact with other medications, including those used to treat HIV. It is important that your personal physician and/or the research nurse or study investigator be aware of all drugs you are taking, including those you buy without a prescription.
• It is expected that etravirine, when combined with two nucleoside analogues, will have strong activity against HIV in people who have never taken an NNRTI in the past.
• In clinical trials, the 800mg twice-daily dose was considered to be the safest and most effective. However, a new formulation of etravirine is being tested. Instead of 800mg twice-daily, the new formulation will allow for a much lower dose: 200mg twice-daily.
• It is not clear how effective etravirine is against strains of HIV that are already resistant to currently available NNRTIs. All of the currently marketed NNRTIs are highly cross-resistant to each other. Test tube data suggest that etravirine might be effective against strains of HIV that are at least partly resistant to any of the approved NNRTIs. But this cannot be determined until information from clinical trials is made available.

2. TMC 114 ( Prezista – Darunavir) 600 mg. Twice a Day (BID)

AIDSmeds.com

What is Prezista?

• Prezista is an anti-HIV medication. It is in a category of HIV medicines called protease inhibitors. Prezista prevents cells infected by HIV from producing new virus. This reduces the amount of virus in your body.
• Prezista must be used with low-dose Norvir® (ritonavir) and in combination with at least two other anti-HIV drugs.
• Prezista, manufactured by Tibotec (a division of Ortho Biotech Products), was approved for the treatment of HIV by the U.S. Food and Drug Administration (FDA) on June 23, 2006. Prezista, combined with Norvir, is only approved for HIV-infected adults who have tried other anti-HIV drug regimens in the past. This includes people who have HIV that is resistant to more than one protease inhibitor. It is not approved for HIV-infected people starting anti-HIV treatment for the first time.

What is known about Prezista?

• Prezista has a different structure than other protease inhibitors and is active against strains of the virus resistant to other protease inhibitors that are currently available.
• The correct dose of Prezista is 600mg twice a day (two 300mg tablets twice daily) plus 100mg Norvir twice a day (one 100mg capsule twice a day). Norvir is necessary to help keep levels of Prezista high in the blood, which is very important for the drug to be effective.
• At the present time, Prezista is only approved for HIV-positive people who have tried other anti-HIV medications in the past. However, once-daily Prezista is currently being studied in clinical trials for HIV-positive people starting treatment for the first time (two 400mg tablets combined with one 100mg Norvir capsule once a day).
• Prezista, combined with Norvir, should be taken with food. The type and amount of food is not important. In other words, Prezista/Norvir can be taken with a full meal or a light snack.
• Prezista is recommended by the U.S. Department of Health and Human Services (DHHS) for HIV-positive people who have tried and failed other protease inhibitors in the past. It is not recommended by the DHHS for patients who are new to anti-HIV treatment or starting a protease inhibitor for the first time.
• Clinical trials have demonstrated that Prezista is an effective option for patients who are not likely to respond to older protease inhibitors, especially when it is combined with other anti-HIV medications that a patient’s virus is still at least partially sensitive to.
• Prezista works best when it is combined with anti-HIV drugs that the virus is still sensitive to. However, this can be challenging for HIV-positive people who have tried several anti-HIV drug regimens in the past. Drug resistance tests, such as genotypic assays and phenotypic assays, and treatment history, can be very useful in figuring out which anti-HIV drugs the virus is still likely to respond to.

TMC114, now called Prezista, has since been licensed in Canada, while access to TMC125 remains restricted, and I am receiving it on expanded release through the clinic.

3. Integrase Inhibitor ( MK0518 – Raltegravir) 400 Mg Twice a Day (BID)
I am receiving this drug via expanded use through the clinic.

Library Thinkquest.com

One of the critical steps in the HIV life cycle is the integration of the virus’s genetic information into the host cell DNA. This allows the host cell to turn into a “HIV factory” and produce many, many virions each hour. The enzyme integrase is the enzyme that accomplishes this task. Integrase inhibitors serve to stop this enzyme.

Integrase inhibitors are oligonucleotides, which are small segments of DNA or RNA that are synthetically prepared. Modified oligonucleotides can serve to block RNA/DNA interactions and modify protein or enzyme synthesis.

One drawback to integrase inhibitors is that it only has one chance to act for each cell. If it fails, any further attempts are futile since the genetic information is already incorporated. In contrast, NRTI’s have thousands of opportunities to act during the process of reverse transcription.

From: Wikipedia

The integrase protein contains three domains:

• an N-terminal HH-CC zinc finger domain believed to be partially responsible for multimerization,
• a central catalytic domain
• a C-terminal.

Both the Central catalytic domain and C-terminal domains have been shown to bind both viral and cellular DNA. Currently no crystal structure data exists with Integrase bound to its DNA substrates.

Biochemical data and structural data suggest that integrase functions as a dimer or a tetramer.

Additionally, several host cellular proteins have been shown to interact with integrase and may facilitate the integration process.

Integration occurs following production of the double-stranded viral DNA by the viral DNA polymerase, reverse transcriptase.

Integrase acts to insert the proviral DNA into the host chromosomal DNA, a step which is essential for HIV replication.

Integrase catalyzes two reactions;

• 3′-end processing, in which two deoxynucleotides are removed from the 3′ ends of the viral DNA.
• the strand transfer reaction, in which the processed 3′ ends of the viral DNA are covalently ligated to the host chromosomal DNA.

Integration of the proviral DNA is essential for the subsequent transcription of the viral genome which leads to production of new viral genomic RNA and viral proteins needed for the production of the next round of infectious virus.

Essentially, integrase is a key step in allowing viral DNA to become a permanent member of the host genome. This integrated proviral DNA is then translated using host cell machinery (see translation) into viral proteins.

HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product. Integrase, therefore, is an attractive potential target for new anti-HIV therapeutics.

In November 2005, data from a phase 2 study of an investigational HIV integrase inhibitor, MK-0518, demonstrated that the compound had potent antiviral activity, and the manufacturer, Merck, is undertaking further clinical studies. ^[1][2]

It is important to note that there are currently no FDA-approved integrase inhibitors available to the public.

4. Norvir (Ritonavir) 100 mg. Twice a Day (BID) Protease Inhibitor

AIDSmeds.com

What is Norvir?

• Norvir is an anti-HIV medication. It is in a category of HIV medications called protease inhibitors (PIs). Norvir prevents T-cells that have been infected with HIV from producing new HIV.
• Norvir is manufactured by Abbott Laboratories. The U.S. Food and Drug Administration (FDA) approved it for the treatment of HIV infection in 1996.
• Norvir is one of the two drugs in Kaletra®. Kaletra contains the protease inhibitor lopinavir and small amounts of Norvir.

What is known about Norvir?

• The official Norvir dose for adults is six 100mg capsules twice a day. However, this dose is rarely used anymore because it is associated with a number of side effects. However, Norvir is still being usually used at much lower doses (one or two 100mg capsules twice a day) to help boost the levels of other protease inhibitors in the bloodstream.
• Norvir has been approved for use in children 1 month of age and older. The dose will depend on the child’s body size. The dose should be between 350 to 400mg per square meter of body area, twice a day. As the child grows, the dose will increase. However, the dose should not exceed 600mg twice a day. The starting dose should be 250mg per square meter of body area. Every 2 to 3 days, the dose should be increased by 50mg, until a total of 400mg per square meter of body area is reached. For children who cannot tolerate a dose of 350 to 400mg per square meter of body area, alternatives to Norvir should be tried. To learn about treatment options for children, click here.
• Norvir, even if low doses are used with another protease inhibitor, should be taken with a meal or light snack.
• Refrigeration of the Norvir capsules is recommended but is not necessary if they are used within 2 months and stored below 77° fahrenheit (25° celsius).
• All of the protease inhibitors are broken down (metabolized) by the same family of enzymes in the liver. In order for the protease inhibitors to be metabolized by these liver enzymes, they must first either slow down its activity or speed it up. All of the currently approved protease inhibitors slow down the activity of these liver enzymes. Norvir is the most powerful of all the protease inhibitors in this regard, even when low doses of the drug are used.

• In turn, Norvir can prevent other protease inhibitors from getting to the enzyme, causing levels of these other protease inhibitors to increase in the bloodstream. This can make the other protease inhibitors more effective against HIV. It also means that lower doses – or less frequent daily doses – of these other protease inhibitors can be taken. This is why low doses of Norvir are often combined with other protease inhibitors: to make them more effective and easier to take.