Didanosine Resistance in HIV-infected Patients Switched from Zidovudine to Didanosine Monotherapy

Kozal, Michael J.; Kroodsma, Kenda L.; Winters, Mark A.; Shafer, Robert W.; Efron, Brad; Katzenstein, David; Merigan, Thomas C.

doi:10.7326/0003-4819-121-4-199408150-00005

Cited by 63 publications

(33 citation statements)

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“…By themselves, these insertions cause low-level resistance to each of the NRTIs, but isolates containing insertions together with T215Y/F and other zidovudine-resistance mutations have high-level resistance to each of the NRTIs (63,218,248,373,406). Insertions at this position are associated with about 20-fold resistance to tenofovir, which is the highest reported level of resistance to this (202,261,338,410) and confers two-to fivefold resistance to didanosine and zalcitibine (368,410) and two-to threefold resistance to abacavir (376). L74V is sufficient to cause virologic failure in patients receiving didanosine monotherapy (202) but additional mutations may be required to cause virologic failure to abacavir monotherapy.…”

Section: Mutations At Codons 65 69 74 and 75mentioning

confidence: 99%

Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

2002

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There are 16 approved human immunodeficiency virus type 1 (HIV-1) drugs belonging to three mechanistic classes: protease inhibitors, nucleoside and nucleotide reverse transcriptase (RT) inhibitors, and nonnucleoside RT inhibitors. HIV-1 resistance to these drugs is caused by mutations in the protease and RT enzymes, the molecular targets of these drugs. Drug resistance mutations arise most often in treated individuals, resulting from selective drug pressure in the presence of incompletely suppressed virus replication. HIV-1 isolates with drug resistance mutations, however, may also be transmitted to newly infected individuals. Three expert panels have recommended that HIV-1 protease and RT susceptibility testing should be used to help select HIV drug therapy. Although genotypic testing is more complex than typical antimicrobial susceptibility tests, there is a rich literature supporting the prognostic value of HIV-1 protease and RT mutations. This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs

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Section: Mutations At Codons 65 69 74 and 75mentioning

confidence: 99%

Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

2002

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“…Increasing evidence, however, indicates that viral resistance and treatment failure are closely linked. [1][2][3][4][5][6][7]75 In recent reports, a minority of those taking complex antiretroviral therapy regimens in whom virologic drug failure was observed appeared to have predominantly wild-type HIV isolates from peripheral blood. [76][77][78][79] Although these findings could be attributed in part to lack of assay sensitivity, other factors may be operative.…”

Section: Use Of Resistance Testing When Changing Therapymentioning

confidence: 99%

“…This has been shown for zidovudine or didanosine, for which resistance is associated with lack of clinical efficacy. 7,75,[87][88][89] These drugs should be replaced when resistance is seen in the setting of confirmed detectable plasma HIV RNA levels. Similar predictive data are emerging for other antiretroviral drugs, eg, phenotypic resistance to abacavir in vitro (ie, Ͼ8-fold increase in IC 50 ) appears to be associated with poor virologic response to abacavir therapy in vivo.…”

Section: Use Of Resistance Testing When Changing Therapymentioning

confidence: 99%

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Antiretroviral Drug Resistance Testing in Adults With HIV Infection

Hirsch

Conway²,

D’Aquila³

et al. 1998

JAMA

527

230

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“…2B). Mutation at position 74 (mostly L74V) is frequently found in patients receiving ddI mono-therapy [48,68,75,76] and also occurs during ABC mono-therapy [56,74]. In the former case, L74V is associated with other mutations (mainly M184V) [77].…”

Section: Emergence Of Resistance Mutationsmentioning

confidence: 96%

Nucleoside and nucleotide inhibitors of HIV-1 replication

Vivet-Boudou

Didierjean

Isel

et al. 2006

Cell. Mol. Life Sci.

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HIV-1 reverse transcriptase (RT) is one of the main targets for antiviral therapy. Two classes of RT inhibitors can be distinguished: those that are nucleoside or nucleotide analogues (sharing the common NRTIs abbreviation) and those that are not. This review focuses on the NRTIs, which are highly efficient in slowing down viral replication and are used in combination regimens. Unfortunately, the current inhibitors do not completely suppress viral replication and due to the high capacity of adaptation of HIV, allow the selection of drug-resistant viruses. Resistance mechanisms to NRTIs have been extensively investigated and can be divided into two types: improved discrimination of a nucleotide analogue relative to the natural substrate or increased phosphorolytic cleavage of an analogue-blocked primer. This knowledge is important both for the development of new drugs designed to target resistant strains and for the development of new antiviral strategies. The NRTIs currently in clinical trials and new developments in this area are also reviewed.

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Didanosine Resistance in HIV-infected Patients Switched from Zidovudine to Didanosine Monotherapy

Cited by 63 publications

References 0 publications

Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

Genotypic Testing for Human Immunodeficiency Virus Type 1 Drug Resistance

Antiretroviral Drug Resistance Testing in Adults With HIV Infection

Nucleoside and nucleotide inhibitors of HIV-1 replication

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