Reference

Reverse transcriptase fidelity and HIV-1 variation

Reverse transcriptase fidelity and HIV-1 variation. Comments. Preston, Bradley D. (Eccles Inst. Human Genetics, Univ. Utah, Salt Lake City, UT 84112, USA). Science (Washington, D. C.), 275(5297), 228-229 (English) 1997 American Association for the Advancement of Science. CODEN: SCIEAS. ISSN: 0036-8075.There are some reagents with their cas registry numbers 9068-38-6 and 134678-17-4 are used in this study. DOCUMENT TYPE: Journal CA Section: 15 (Immunochemistry) Section cross-reference(s): 1, 3, 10 A polemic in response to M. A. Wainberg et. al. (ibid. 1996, 271, 1282). Wainberg et al. hypothesized that increased reverse transcriptase fidelity could possibly account for slowed emergence of epitope variants obsd. in patients treated with lamivudine (3TC) and the failure to detect secondary drug-resistant variants during growth of 3TC resistant HIV-1 in culture. In comparison, Coffin et al. argues that the proportion of variant genomes in a replicating population of HIV-1 is modeled as a function of virus mutation rate, fitness of the variant relative to the wild type and the no. of replication cycles. Here we present modeling results that suggest that the frequency of genetic variants arising in a HIV-1 population is influenced by many factors, including mutation rate, fitness, population size, no. of replication cycles and competition. Despite mutation rate providing variation, the overall compn. of a large rapidly replicating HIV-1 population is most likely detd. by relative fitness and not mutation rate. .

Rational approaches to resistance: Nucleoside analogs

Rational approaches to resistance: Nucleoside analogs. Mayers, Douglas (Walter Reed Army Institute Research, Bethesda, MD 20889-5000, USA). AIDS (London), 10(Suppl. 1), S9-S13 (English) 1996 Rapid Science Publishers. CODEN: AIDSET. ISSN: 0269-9370. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review with ~32 refs. The purpose of this study is to review knowledge of drug-resistance patterns to nucleoside HIV reverse transcriptase inhibitors and how this can be used to advantage in patient management. The speed of emergence of HIV-1 drug resistance is dependent on host, viral and drug factors. Resistance to zidovudine develops over months to years, and is assocd. with mutations in HIV reverse transcriptase at positions 41, 67, 70, 215 and 219. Redns. in susceptibility to didanosine, zalcitabine and stavudine develop more slowly and are lower than those seen with zidovudine. Resistance to lamivudine develops rapidly, in weeks to months; selection of a pre-existing mutated viral strain results in a 1000-fold redn. in susceptibility. There is some cross-resistance between nucleoside antiretroviral agents, particularly among didanosine, zalcitabine and lamivudine. Some agents induce mutations that reverse or suppress zidovudine resistance; combination therapy with these drugs may delay the emergence of multi-drug-resistance, but the mutational flexibility of the HIV-1 virus means that drug resistant isolates will eventually develop. Combining HIV protease inhibitors that strongly suppress viral replication with nucleoside inhibitors also delays the emergence of resistance. Widespread use of nucleoside HIV reverse transcriptase inhibitors that incompletely suppress viral replication has led to the emergence of resistant viral strains, with a consequent risk of transmission of drug-resistant virus. 69655-05-6 and 134678-17-4 are just another two chemicals used in this study. Combinations of protease inhibitors and reverse transcriptase inhibitors may slow viral replication sufficiently to prevent generation of resistant virus, to extend the duration of antiviral activity and increase the benefit to patients. .