Rate of Thymidine Analogue Resistance Mutation Accumulation With Zidovudine- or Stavudine-Based Regimens

Kuritzkes, Daniel R.; Bassett, Roland L.; Hazelwood, J. Darren; Barrett, H.; Rhodes, Ruth A; Young, Russell; Johnson, Victoria A.; Teams, Adult Actg Protocol

doi:10.1097/00126334-200405010-00008

Cited by 32 publications

(31 citation statements)

References 15 publications

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“…As previously shown, there was no difference in the emergence of TAMs in subjects who received zidovudine versus stavudine. 46 The strengths of this study are the prolonged period of observation during virologic failure on a stable antiretroviral regimen and the frequency with which resistance genotypes were obtained. We believe that the differential rate of emergence of TAMs and major protease inhibitor mutations is not likely to be attributable to variances in adherence to these medications, especially because there was no correlation between the emergence of resistance mutations and the observed virologic responses.…”

Section: Discussionmentioning

confidence: 99%

“…31 Thus, TAMS were defined as the specified mutations at amino acid positions 41, 67, 70, 210, 215, and 219. Major protease inhibitor resistance mutations were defined as those at amino acid positions 30,46,48,50,82,84, and 90, and minor resistance mutations were defined as those at amino acid positions 10, 20, 24, 32, 33, 36, 47, 53, 54, 63, 71, 73, 77, and 88. This study used plasma specimens obtained from patients who had undergone HIV pVL testing at the VA Greater Los Angeles Healthcare System between August 1996 and August 2004. Since August 1996, aliquots of plasma from all patients undergoing pVL analyses at this facility have been routinely stored at − 70° C. All genotyping was done using the TruGeneassay (Bayer, Berkeley, CA).…”

Section: Methodsmentioning

confidence: 99%

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Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Goetz¹,

Ferguson²,

Han³

et al. 2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective-We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure.Design-Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure.Results-The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4 + cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used.Conclusions-Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Goetz¹,

Ferguson²,

Han³

et al. 2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…The M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E mutations are known as thymidine analogue mutations (TAMs). TAMs are a subset of NAMs that are selected by the thymidine analogues zidovudine (ZDV) and stavudine and that are associated with cross-resistance to most currently approved NRTIs (4,12,(14)(15)(16). Furthermore, some NRTI resistance mutations have been preferentially associated with certain TAM profiles (20).…”

mentioning

confidence: 99%

Variations in Reverse Transcriptase and RNase H Domain Mutations in Human Immunodeficiency Virus Type 1 Clinical Isolates Are Associated with Divergent Phenotypic Resistance to Zidovudine

Ntemgwa

Wainberg

Oliveira

et al. 2007

Antimicrob Agents Chemother

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Mutations in the RNase H domain of human immunodeficiency virus type 1 RT have been reported to cause resistance to zidovudine (ZDV) in vitro. However, very limited data on the in vivo relevance of these mutations in patients exist to date. This study was designed to determine the relationship between mutations in the RNase H domain and viral susceptibility to nucleoside analogues. Viruses harboring complex thymidine analogue mutation (TAM) and nucleoside analogue mutation (NAM) profiles were evaluated for their phenotypic susceptibilities to ZDV, tenofovir (TNF), and the nonapproved nucleoside reverse transcriptase inhibitors (NRTIs) ␤-2,3-didehydro-2,3-dideoxy-5-fluorocytidine (Reverset), ␤-D-5-fluorodioxolane-cytosine, and apricitabine. As controls, viruses from NRTI-naïve patients were also studied. The pol RT region (codons 21 to 250) of the viruses were sequenced and evaluated for mutations in the RNase H domain (codons 441 to 560) and the connection domain (codons 289 to 400). The results showed that viruses from patients failing multiple NRTI-containing regimens had distinct TAM and NAM profiles that conferred various degrees of resistance to ZDV (0.9-to >300-fold). Sequencing of the RNase H domain identified five positions (positions 460,468, 483, 512, and 519) at which extensive amino acid polymorphisms common in both wild-type viruses and viruses from treated patients were identified. No mutations were observed at positions 539 and 549, which have previously been associated with ZDV resistance. Mutations in the RNase H domain did not appear to correlate with the levels of phenotypic resistance to ZDV. Although some mutations were also observed in the connection domain, the simultaneous presence of the L74V and M184V mutations was the most significant determinant of phenotypic resistance to ZDV in patients infected with viruses with TAMs.

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“…Estas mutaciones confieren una susceptibilidad reducida a todos los aprobados NRTI sin embargo este grado depende de la resistencia cruzada y el número de mutaciones involucradas. [6,7] Las mutaciones de la transcriptasa inversa E44D y V118I no fueron presentes en los genotipos de este estudio. Estas mutaciones tienen un papel adyuvante en el aumento de la resistencia al NRTI con presencia de TAMs.…”

Section: Discussionunclassified

“…Estudios, en Brasil, han demostrado una prevalencia de hasta 2,2% de resistencia a IP, 2,4% a ITRN y 2,1% a NNRTI. 7 Las mutaciones reportadas más frecuentemente en los trabajos mencionados, poco difieren a las encontradas por nuestro trabajo, la V82A, la A71V muy frecuente. En los IP.…”

Section: Discussionunclassified

Resistencia a medicamentos Anti-rretrovirales (ARV) en pacientes con segundo fracaso terapéutico en un programa de VIH, Colombia

Sierra

Pinzón

Cortes

et al. 2014

RFS

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Objetivo: Describir la resistencia a los medicamentos antirretrovirales en pacientes con segundo fracaso terapéutico en un Programa de VIH entre enero de 2011 a Diciembre de 2011. Material y métodos: Se realizó un estudio descriptivo, retrospectivo de serie de casos. Donde se describieron las mutaciones del VIH, características clínicas y hallazgos de laboratorio de los pacientes con resistencia en segundo fracaso terapéutico. Resultados: Se identificaron 30 pacientes con segundo fracaso terapéutico en el periodo de estudio. El tiempo promedio de uso de Terapia Anti-rretroviral por paciente fue de 77,2 meses (DS= 56). A 12 pacientes se les realizaron tres cambios de esquema anti-rretroviral por fracaso terapéutico y otros 2 pacientes hasta cuatro cambios de esquema. Las mutaciones más frecuentes fueron las primarias a Inhibidores de Proteasa (M46I, I54V, L10I) y a Inhibidores de Transcriptasa Inversa Análogos de Nucleósidos (Abacavir, Didanosina y Zidovudina, Estavudina).

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Rate of Thymidine Analogue Resistance Mutation Accumulation With Zidovudine- or Stavudine-Based Regimens

Cited by 32 publications

References 15 publications

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Variations in Reverse Transcriptase and RNase H Domain Mutations in Human Immunodeficiency Virus Type 1 Clinical Isolates Are Associated with Divergent Phenotypic Resistance to Zidovudine

Resistencia a medicamentos Anti-rretrovirales (ARV) en pacientes con segundo fracaso terapéutico en un programa de VIH, Colombia

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