HIV Treatment And Combinations
What are 'nucleosides'?
Nucleosides is a shortened, abbreviated way of saying nucleoside reverse transcriptase inhibitors. Nucleosides are a class of anti-retroviral drugs. The first anti-retroviral drug - AZT, Zidovudine, or Retrovir, it has three names - is a nucleoside reverse transcriptase inhibitor. Now we have a half a dozen of them, other nucleosides: d4T, ddI, abacavir, tenofovir, 3TC, FTC, etc. The nucleosides prevent the virus RNA being turned into virus DNA by the viral enzyme, reverse transcriptase. That's a step that has to occur in the replication of HIV before the HIV genetic material can infect the host's Cd4 cell nucleus. If that can't happen, the virus can't take over the Cd4 cell, and can't reproduce itself, because it has to use the cell to reproduce itself. This blocks infection of the Cd4 cell.
What are 'non-nucleosides'?
Non-nucleosides anti-inhibitors are drugs that inhibit that same enzyme (reversed transcriptase) inhibited by nucleosides, but do it in a different way. Nucleosides pretend to be building blocks of DNA, but they are altered building blocks, which prevent the completion of the task. Non-nucleoside anti-inhibitors don't pretend to be building blocks of DNA. They just glom on to the reverse transcriptase inhibitor enzyme and stop it working. They work at the same phase of HIV replication. They prevent viral DNA being formed, and they therefore prevent the virus infecting the CD-4 cell and being able to make copies of itself. There are only two non-nucleoside anti-inhibitors available at the moment, and they are Nevirapine (Viramune is its trade name) or Efavirenz (trade name Sustiva). There are some second-generation non-nucleoside anti-inhibitors in development. One of them is called Etravirine, and that's an exciting compound which we hope will be FDA-approved during this year, 2007. Etravirine, the second-generation NNLTI, will treat viruses that become resistant to Nevirapine and Efavirenz. It also is a drug that requires the virus to make several mutations before the virus can become resistant to Etravirine, whereas the virus has to make only one mutation to become resistant to Nevirapine and Efavirenz. So, it's definite progress.
What are 'protease inhibitors'?
Protease inhibitors are designer drugs, invented by clever scientists in various drugs companies who took HIV's protease enzyme, crystalized it, found the structure of it, and designed a molecule that would glom onto it and block it's functioning. The HIV protease enzyme works at the end of the viral repercation cycle in the CD4 cell. The cell has already been infected with HIV. The cell has already been making the virus components and some of those virus components are proteins. The HIV viral protease enzyme has to cut up those proteins so that the virus can be assembled and removed from the cell. The protease inhibitor stops it working, so it prevents the infected cell, the already infected cell, from producing live virus. These are the basics behind protease inhibitors.
What are 'CCR5 entry inhibitors'?
What is 'HAART' or 'cocktail medications'?
"HAART" means highly active antiretroviral therapy. "HAART" is essentially just antiretroviral therapy. It's three drugs combined to make highly effective therapy.
How effective is HAART compared to the original HIV medication?
HAART these days is very effective. The drugs we have are very potent. A major development occurred 5-8 years ago when we started to boost protease inhibitors with riton-avir that gave us very powerful drugs. Two nucleosides and a boost protease inhibitor, and two nucleosides and a non-nucleoside, are very potent therapies and these days we don't expect people to break through these treatments unless they don't take them well. When we began HAART with unboosted protease inhibitors some 10 years ago, even if people took the drugs perfectly there was a certain number that would break through. Now, if the drugs are taken perfectly, it is very unlikely people will break through.
What is a typical combination of HAART?
We've found that in any retroviral therapy it's important to have three active drugs if at all possible. It seems logical that it would work best if you had one drug of each class but three drugs from one class can work fairly well. Three nucleosides can work fairly well, although not quite as well. What we normally do is use two nucleosides and an NNITI, or two nucleosides and a protease inhibitor. However, there are new classes of drugs coming out and this year we see the first integrase inhibitors and the first CCR-5 inhibitors. So, it may be that regimens in the future will contain perhaps two nucleosides and a CCR-5 inhibitor, or two nucleosides and an integrase inhibitor, or an integrase inhibitor and a protease inhibitor, or a protease inhibitor and a CCR-5 inhibitor. There will be many different combinations in the future.
How do I choose which medication to take for my HIV?
What is 'Atripla'?
Atripla is a new combination tablet which has three drugs in one tablet. It has tenofovir, which, when it's separately marketed, is called Viread. Atripla also has FTC, which when it's separately marketed is called Emtriva. Thirdly, atripla has efavirenz, which when it's separately marketed is called Sustiva. It has all those three medications in one pill, and the pill is called Atripla.
Is Atripla as effective as the traditional cocktail medication?
Atripla is as effective as the traditional HAART medication because it IS the traditional HAART medication. The traditional HAART is to give three drugs separately, like Viread, Emtriva, and Sustiva. Giving Atripla is exactly the same as giving Viread, Emtriva, and Sustiva, except that all three pills are just jammed into one.
Should I switch to Atripla if I am already on HAART?
A lot of patients ask if they're already on anti-etroviral therapy, if they can switch to Atripla. Well the answer is some can switch to atripla and some can't. If they've never become resistant to anything, yes they could switch to atripla. But if they have been on drugs before and become resistant to nucleotides or become resistant to non-nucleotides, then they can't use Atripla.
