Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission

Jackson, J. Brooks; Becker-Pergola, Graziella; Guay, Laura; Musoke, Philippa; Mracna, Martin; Fowler, Mary Glenn; Mofenson, Lynne; Mirochnick, Mark; Mmiro, Francis; Eshleman, Susan H.

doi:10.1097/00002030-200007280-00001

Cited by 178 publications

(97 citation statements)

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“…It is an indication of a high probability of the evolution of widespread resistance to protease and reverse transcriptase inhibitors in this population where subtype G and its recombinants are prevalent. A preliminary study had shown that the niverapine resistance mutations (K103N) were readily selected in Ugandan women who received a single dose prophylactic regimen at the onset of labor in the Phase I/II trial HIVNET 006 (Jackson et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

Lar¹,

Lar²,

Bemis³

et al. 2007

Afr. J. Biotechnol.

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To determine HIV-1 subtypes and antiretroviral drug resistance mutations for 16 infected, pregnant women in Jos, Nigeria, part of pol (1040 bp) was amplified from patient PBMC DNA, sequenced and analyzed. Eight of the samples were subtype G, three were CRF02_AG and 2 were unique recombinant forms (URF) between G and CRF02_AG. The remaining consisted of 3 different strains: one was subtype C, and the other 2 were unrelated URF. Nearly full-length genome sequences were completed for 6 of the strains: 4 subtype G and 2 CRF02_AG. In the 14 drug-naïve subjects, no primary resistance-associated mutations were found, but secondary mutations were identified in 7 different codons of the gene coding for protease: PR K20I, M36I, L63A/P/V, V82I, L10M/I and I93L. In addition, the K238R mutation was identified in the reverse transcriptase gene of 3 viruses. The PR K20I and M36I mutations occurred in all of the strains, and the L10M and V82I mutations occurred only in subtype G. The mutation, I93L, was carried by subtype C viruses. Two of the women that had prior niverapine treatment, had primary resistance-associated mutations, RT M184V and K103N, archived in their proviral DNA several months after treatment cessation. The study reports a predominance of clade G and CRF02_AG, and provides many more examples of nearly full-length genome sequences for subtype G viruses from Nigeria. The ubiquitous presence of PI secondary resistance-associated mutations, as well as primary resistanceassociated mutations in 2 previously treated women, underscores the need to ensure adherence compliance to treatment.

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Section: Discussionmentioning

confidence: 99%

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

Lar¹,

Lar²,

Bemis³

et al. 2007

Afr. J. Biotechnol.

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“…Резистентность к ИП/р требует 5-8 мутаций (вы-сокий генетический барьер), поэтому, чтобы она сфор-мировалась, нужны одновременно и активная реплика-ция вируса, и высокая концентрация препарата. Только тогда у вируса с мутациями появляется эволюционное преимущество [15]. Однако ИП/р способны в достаточ-ной мере подавлять репликацию, чтобы воспользовать-ся своим преимуществом вирус не смог.…”

Section: влияние приверженности к терапии на развитие резистентностиunclassified

Selection of an Antiretroviral Regimen Based on the Resistance Data

2017

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Борьба с глобальной эпидемией вируса иммуно-дефицита человека (ВИЧ) в последнее десяти-летие дала свои плоды. По оценкам ВОЗ, число новых случаев инфицирования ВИЧ в 2015 г. сократи-лось на 38% по сравнению с 2001 г. и достигло 2,1 млн. Число людей, умирающих от ассоциированных с ВИЧ причин, также сократилось по сравнению с 2003 г. на 43% и достигло 1,1 млн в 2015 г. [1]. В значительной степени это стало результатом расширения доступа к антиретровирусной терапии. К концу 2015 г. лечение получали более чем 17 млн человек, живущих с ВИЧ. На основе этих достижений и полученного опыта ВОЗ строит глобальную стратегию сектора здравоохранения по ВИЧ на 2016-2021 гг. Основные целевые показате-ли этой программы сформулированы как «90-90-90». Это означает, 90% людей, живущих с ВИЧ, должны знать о своем статусе; 90% людей, живущих с ВИЧ, дол-жны получать антиретровирусную терапию (АРТ); 90% людей, живущих с ВИЧ и получающих лечение, должны достигнуть вирусной супреcсии.Одним из препятствий на пути достижения целей глобальной стратегии является вирусная резистент-ность. Ее распространенность на сегодняшний день изучена недостаточно, особенно в регионах, где про- One of the main obstacles to achieving the goal is HIV resistance to antiretroviral therapy. It occurs when the virus mutates and affinity of active ingredients of drugs for the corresponding viral proteins is reduced. Drugs differ by the genetic barrier. Non-nucleoside reverse-transcriptase inhibitors lose their ability to inhibit the replication after a single mutation, and ritonavir-boosted protease inhibitors -after 5--8th mutation. The key factor for adequate viral suppression and reduction of risks is good adherence to treatment. Medication non-adherence creates a favorable environment in the body for the evolution of the virus. In the Russian Federation, the prevalence of primary resistance reaches 6.02%, and poor adherence equals 26%. The data and the results of examinations for mutations should be considered when selecting an antiretroviral regimen and approach to patient to improve adherence.

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“…Subtype G strains are less susceptible in vitro to protease inhibitors (PIs), the rate of occurrence of nevirapine resistance-associated mutations after a single dose is significantly higher in women with HIV-1 subtype C than in women with subtype A or D 81,82 . Nevirapine prophylaxis used in the HIVNET 012 66 has been reported to result in selection of single point mutations strongly associated with high resistance to non-nucleoside reverse transcriptase inhibitors that were detectable in 19% of the mothers and 46% of the infants 83 . By contrast with HIVNET 012 ® , where intra partum and neonatal exposure to nevirapine or zidovudine was limited, the PETRA ® interventions led to ongoing maternal exposure to zidovudine plus lamivudine from 36 weeks gestation.…”

Section: Drug Resistance Viral Subtypes and Implications On Mtctmentioning

confidence: 99%

The Changing Trends of HIV Subtypes and Its Implication on Mother-to-Child Transmission

Kiptoo¹

2011

Recent Translational Research in HIV/AIDS

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Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission

Cited by 178 publications

References 11 publications

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

Selection of an Antiretroviral Regimen Based on the Resistance Data

The Changing Trends of HIV Subtypes and Its Implication on Mother-to-Child Transmission

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