How does HIV become resistant to an analogs action of substituting for its respective nucleoside in DNA?

Question

How does HIV become resistant to an analogs action of substituting for its respective nucleoside in DNA?
Drugs used for "anti-viral" HIV medication often include AZT, ddI, ddC, 3TC as part of the HAART regimen. These drugs are chemical phonies of the nucleosides that build DNA chains. If HIV has to hi-jack a cells machinery in order to replicate, how is it possible that HIV can mutate so to prevent the cell from substituting an analog in DNA synthesis? It is clear though, that these chemicals do in fact do a better job of what HIV is *said* to do- Kill cells.

jewel64052 · Accepted Answer

AZT is the most commonly prescribed anti-HIV treatment. Its brand name is Retrovir. It is in the class of anti-HIV drugs known as nucleoside analogs. A number of other nucleoside analog drugs which have a similar method of action are:

ddI (Videx), 
ddC (Hivid), 
d4T (Zerit), 
3TC (Epivir).
A newer class of anti-HIV drugs are protease inhibitors. The approved protease inhibitors are:

saquinavir (Invirase), 
ritonavir (Norvir), 
indinavir (Crixivan). 

Recently completed studies indicate that combinations of these anti-HIV drugs are much more effective than AZT alone in preventing disease progression and death. 
The initial studies which demonstrated the benefits of combination therapy were called DELTA and ACTG 175. These studies compared combinations of AZT with ddI, and AZT with ddC, to AZT taken alone. The studies involved several thousand patients. Patients taking the combinations survived longer and had less disease progression than those taking AZT alone. 

Since these studies were conducted, protease inhibitors have become available. A new test for measuring how well anti-HIV drugs are combating the disease has also just become available. The viral load tests measure the amount of HIV in the blood. Researchers are finding that the level of HIV in the blood is linked to the severity of disease. A study has shown that using drug treatments to lower the level of HIV can reduce the chances of disease progression. 

Combination anti-HIV treatment has become the standard of care for patients with HIV. It has not yet been determined which of the anti-HIV drug combinations are most effective. What is clear is that the stronger the anti-HIV effects of a combination therapy, the less likely it is that HIV will become resistant to the effects of the drugs. When HIV becomes resistant to a drug, that drug no longer works against the virus. Combinations usually include a protease inhibitor, 3TC, and one other nucleoside analog anti-HIV drug such as AZT or d4T. 

Combinations of protease inhibitors are currently in trials. A trial of ritonavir and saquinavir is ongoing, and a trial of saquinavir and indinavir is planned. Data from just six weeks of the saquinavir and ritonavir trial has been presented. Doses studied so far have been 400 mg of saquinavir twice daily with ritonavir at either 400 mg twice daily, or the standard ritonavir dose of 600 mg twice daily. 


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How does HIV become resistant to an analogs action of substituting for its respective nucleoside in DNA?