Exam I Study Guide
Supplement
HIV and AIDS
Virological mayhem
The causes of AIDS were long controversial because of the response of the HIV virus to treatment and its unusual presentation. As a result many thought HIV resulted from non-viral sources, and until fairly recently some African nations rejected Western treatments as politically and economically driven. The work that convinced most researchers that HIV was unquestionably the cause resulted from tour de force research published in 1995.Read the summary/evaluation of this research in Nature News and Views [Nature 373 pp. 102 (12 January 1995)] of these seminal articles in our understanding of HIV and in particular the disease state AIDS by Wei et. al. and Ho et. al.*Consider the following:
- The actions of the various drugs-what they are doing.
- The viral responses (types of mutations, enzymes involved) to the drugs and how these responses were determined (techniques).
- Because HIV is an RNA retrovirus there is a high error rate in its reproduction, so many point mutations occur, a small portion of which can be advantageous in allowing viral strains to overcome individual drugs via modified enzymes. As a result some strains will be drug resistant resulting in a change in the viral population in a short time and resurgence of the HIV infection following initial reduction with individual drug use.
- The conclusions from this research regarding:
- the nature of the HIV infection,
- HIV targets CD4 immune cells, reducing host immune response as infection proceeds.
- High viral turnover (life cycle 1-2 days) with host producing extreme viral loads. (HIV production of 108–109 virions/day in AIDS patients
- Poor fidelity leads to extreme diversity in HIV viral population. (>108 variants in AIDS patients, >106 in asymptomatic patients)
- how HIV responds to challenges, why HIV always "wins,"
- High viral production rate and great diversity allows virus to overcome host responses and single drug therapies. (t1/2 ≈2 days for emergence of drug resistant virus, essentially same as clearance/production rate)
- About 2x109 CD4 T cells produced /day, but lose slightly more to give a net loss of about 107–108/day, so virus gradually “wins” by higher reproduction/CD4 destruction rate than body can replace (remember, ALL biosynthesis/growth is accomplished by the infected individual, so both processes drain host energy levels.
- “Hidden” infection (deep in secondary lymphoid organs) in the form of viral genomes integrated into host genome means even if all viral particles are eliminated in therapy, it can come back by re-infection from reservoir.
- implications for clinical control of this virus.
- Clinically means no long terms cure with current strategies—patients must undergo life-long continuous drug therapy.
- What is the prognosis for AIDS if you live in an advanced country and have good insurance?
- Current multi-drug treatments appear to allow lon- term “healthy” co-existence with HIV infection. However, this assumes the economic ability to afford lifetime treatment (“good” insurance – an uncertain situation in the U.S. given current political battles etc.).
- What is the difference between HAART and a “cure”?
- HARRT controls the infection, it does NOT eliminate the virus, so cessation of drug treatment generally results in a return of symptoms and death if treatment is not resumed.
• How likely is a cure in the forseeable future? Defend your position.
- This is an open question with multiple defendable positions—you will find respectable, intelligent folks in the community arguing both sides. So credit depends on the QUALITY of your argument, NOT your position.
Last modified 24 February 2012