Article abstract-Background: The goal of highly active antiretroviral therapy in HIV-infected patients is to reduce plasma viral load (VL) below quantifiable levels. Mutations associated with drug resistance within the HIV-1 genome can limit therapeutic success. Low VL implicates a low risk ofemergence of resistant mutants. Whether there is divergent development of HIV strains in different biologic compartments is not understood. Methods: The authors studied VL and the occurrence of mutations conferring resistance in viral genomes isolated from blood and CSF samples of 23 HIV-infected patients. They determined sequences of HIV-1 RNA by reverse transcriptase PCR amplification and directsequencing. They measured resistance to antiretroviral drugs genotypically by detection of drug-related point mutations and VL by a branched-DNA assay. Results: Amplification of HIV was successful even in patients with plasma or CSF VL below detection limit. VL was considerably lower in CSF as compared with blood (p < 0.0001). There was no correlation between CSF and plasma VL. The mutational patternin viral copies derived from blood and CSF was not identical. Ten (9%) of the total number of 118 mutations associated with drug resistance occurred in blood isolates only; 14 (11%) were detected exclusively in CSF strains. Conclusion: There is evidence for viral replication at HIV RNA levels less than 50/mL. The results suggest divergent evolution of HIV-1 in different biologic compartments. Thepresence of resistant mutants in the CSF may escape regular diagnostic in blood. Therapeutic success may fail after adapting therapy to genotypic resistance patterns detected in one compartment only.
In biology, a change in the genes produced by a change in the DNA that makes up the hereditary material of allliving organisms. It can be a change in a single gene or a change that affects sections of chromosomes. In the process of DNA replication, which takes place before any cell divides, the two halves of DNA separate and new halves are made. Because of specific base pairing, the inherited information is copied exactly. Despite this, rarely, a mistake occurs and the sequence of bases is altered. Thischanges the sequence of amino acids in a protein. This is mutation, the raw material of evolution. The consequences of mutation are varied. Due to the redundancy built into genetic code many mutations have no effect upon DNA functions. Genes describe how to make proteins. As a result of mutation a protein may not be produced, may be produced but act abnormally, or remain fully functional. Only a fewmutations improve the organism's performance and are therefore favoured by natural selection. Mutation rates are increased by certain chemicals and by ionizing radiation. Common mutations include the omission or insertion of a base (one of the chemical subunits of DNA); these are known as point mutations. Larger-scale mutations include removal of a whole segment of DNA or its inversion withinthe DNA strand. Not all mutations affect the organism, because there is a certain amount of redundancy in the genetic information. If a mutation is ‘translated’ from DNA into the protein that makes up the organism's structure, it may be in a non-functional part of the protein and thus have no detectable effect. This is known as a neutral mutation, and is of importance in molecular clock studiesbecause such mutations tend to accumulate gradually as time passes. Some mutations do affect genes that control protein production or functional parts of protein, and most of these are lethal to the organism.
Viruses, Vaccines, and Evolution of Influenza
Since viruses have such high mutation and reproductive rates, they can adapt to changing environments quite well. Indeed, since the only...