HIV drug resistance

HIV drug resistance occurs when microevolution causes virions to become tolerant to antiretroviral treatments.

Limited effects of current drugs
HIV develops resistance when it evades the effects of these treatments. Nearly all drugs currently used to treat HIV eventually stop working and the infected patient’s immune system is damaged to the point of AIDS. A recent study estimated the percentage of the American HIV positive population with some form of drug resistance to be 76.3%. Certain intrinsic features of HIV facilitate its widespread resistance, most importantly its extremely high mutation rate.

Developing resistance
As a retrovirus, HIV uses the enzyme reverse transcriptase to synthesize DNA from its RNA genome and lacks a mechanism for correcting errors made while reproducing its genome. As a result, HIV replicates its genome with the highest known mutation rate of any 'living' organism. This creates an ideal situation for natural selection to act on the HIV population, as genetic variation is the raw material for natural selection.

These mutations accumulate over generations and in populations, resulting in the great genetic variation within populations of HIV, and an increased probability of a virion developing an evolutionary selective advantage over other virions. Natural selection then acts on HIV by selecting for virions with higher fitness, as all others are eventually killed off by drug treatments. The virions that are able to escape the harmful effects of the drug then create an entirely new, drug resistant population.

The virions reproduce until the patient has a population of viruses as large as they originally did before treatment reduced these numbers. This creates a cycle in which patients first experiences success with treatment, as their viral levels decrease, then experiences a decline in treatment effectiveness as the virus develops resistance and rebuilds its population of virus particles.

Contemporary treatment issues
Currently, resistance occurs in all antiretroviral treatments. This has resulted from HIV evolving in response to selection from antiretroviral drug treatments that eliminate all but the most fit viruses. Current medical and scientific opinion is mixed on the most effective treatment methods, but is focused on drug cocktails and the importance of first-line regimens.

The World Health Organization advocates a public-health approach rather than an individual-based approach to HIV treatment in order to make treatment more uniform and more available to all patients throughout the world. Among treatment methods, the World Health Organization acknowledges the importance of successful first-line treatments.

First-line treatments are known to affect the virus’ future response to other treatments, making the effectiveness of first-line treatments an issue of vital importance. The most successful treatments are combinations of three drugs used simultaneously, as this greatly reduces the probability of the virus developing resistance.

Effect of human intervention
In the battle between human antiretroviral drug therapy techniques and HIV microevolution, HIV is currently outpacing human antiretroviral drug therapy techniques: all treatments ultimately end in HIV developing resistance to the treatment. Some scientists believe humans are pushing the microevolution of HIV toward more resistant viruses.

For example, some researchers claim that human drug therapies are accelerating retrovirus evolution through drug therapies that select for resistant viruses. Human intervention on HIV evolution through drug therapies has also been accused of being detrimental to the ultimate goal of finding a permanent cure for HIV.