The good news is that HAART has successfully treated HIV-positive patients, givi

Question

The good news is that HAART has successfully treated HIV-positive patients, giving them extended lifespans, allowing the immune system to regain control, and decreasing virus loads. The bad news is that HIV is a smart virus; HIV has developed mechanisms to overcome the blocks imposed by drug treatments.

Through a microevolutionary process, HIV variants that are resistant to the intended inhibition are able to replicate and produce more virus. Over time, in the presence of a drug such as AZT, random mutations may develop and be selected for that allow these variants to be resistant to the effects of AZT. These drug resistant variants have greater fitness and can replicate in a person even in the presence of a drug. Specifically, mutations in reverse transcriptase (RT) develop in the presence of AZT. These variants allow HIV to continue to replicate in human T cells. HIV variants may only contain a single amino acid change in the protein sequence to render an anti-HIV drug ineffective.

For many years, doctors emphasized the necessity for strict compliance with prescribed HAART treatment regimens. Recently, a controversial new therapy called structured treatment interruption (STI) has been suggested to HIV-positive patients by their physicians. STI refers to the practice of alternating time spent on antiretroviral drugs with time spent off drugs, and each cycle may last anywhere from several days to months. However, it is not recommended for all HIV-positive patients. The theory behind STI is that the alternating periods of HAART treatment with regulated withdrawals of drug therapy may serve as a means of inducing immune system control of HIV.

Questions:

1. How are natural selection and microevolution illustrated in this scenario? Identify the genetic basis for HIV evolutionary change, the selective pressure, and the resulting adaptation. What happens to mutants that are able to escape detection by the immune system?

2. Describe how mutations could lead to drug resistance in the RT enzyme. Include phsyical, molecular, and biochemical reasons.

Explanation / Answer

1. Any mutation that appears during the viral replicative cycle forms the genetic basis for evolutionary change. The immune system of the host, the response of the host T and B cells as well as the response of anti bodies.

Variants that have a higher fitness level will escape detection by the host immune system.

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