by Eugene Jacquescoley DO PhD

Created on: January 16, 2007   Last Updated: May 02, 2007

Each year at the HIV Resistance Conference, the issue of non-adherence or (non-compliance) and genotyping surfaces as it relates to HIV treatment regimens. In an effort to vigorously address this issue, resistance or phenotype testing has gained traction.

As genotyping procedures have increasingly become more sensitive and complex, HIV scientists and physicians are finding new clinical approaches to treat compromised patient populations on Non-nucleoside transciptase inhibitor (NNRTI) classes of drugs. Further, as age demographics play a vital role in these populations, understanding phenotype/resistnace panels for regimen changes is paramount.

As many of you may know, genotyping refers to the process of determining the genotype of an individual with a biological assay. Current methods of doing this include PCR, DNA sequencing, and hybridization to DNA chips or beads. The technology is intrinsic for test on father-/motherhood and in clinical research for the investigation of disease-associated genes. Further, the genotype is the specific genetic makeup (the specific genome) of an individual, in the form of DNA (Cohen et al). Together with the environmental variation that influences the individual, it codes for the phenotype of that individual. Non-hereditary mutations are not classically understood as representing the individuals' genotype. Hence, scientists and doctors sometimes talk for example about the (geno)type of a particular cancer, thus separating the disease from the diseased. While codons for different amino acids may change in a random mutation (changing the sequence coding a gene), this doesn't necessarily alter the phenotype (Cohen et al, 2006).

NNRTI's are a class of anti-HIV drugs. When one NNRTI is used in combination with other anti-HIV drugs usually a total of 3 drugs then this combination therapy can block the replication of HIV in a person's blood. NNRTIs, sometimes referred to as "Non-Nucleoside Analogues" or "non-nukes" (Cohen et al, 2006) for short prevent healthy T-cells in the body from becoming infected with HIV (AIDSMEDS). When HIV infects a cell in a person's body, it copies it's own genetic code into the cell's DNA. In this way, the cell is then "programmed" to create new copies of HIV. HIV's genetic material is in the form of RNA. In order for it to infect T-cells, it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.NNRTIs attach themselves to reverse transcriptase and prevent

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