Discrimination of lamivudine resistant minor HIV-1 variants by selective real-time PCR

Bergroth, Tobias; Sönnerborg, Anders; Yun, Zhibing

doi:10.1016/j.jviromet.2005.03.007

Cited by 13 publications

(18 citation statements)

References 15 publications

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“…Selective Real-Time PCR SPCR was performed as described previously , using primers SPCRWU (200 nM), SPCRGTG (100 nM), SPCRATA (100 nM), SPCRWD30v2 (200 nM) and probe SPCRPROBE (200 nM) [Bergroth et al, 2005]. The cut-off values for the SPCR assay had previously been set to 1.0% (SPCRGTG) and 0.2% (SPCRATA) , but were calculated individually for samples with low viral loads.…”

Section: Preparation Of Patient Samplesmentioning

confidence: 99%

“…For this purpose selective realtime PCR (SPCR) [Bergroth et al, 2005] was used, which can detect levels of resistance mutations as low as 0.2% of the viral population, together with direct sequencing to determine the occurrence of the HIV-1 reverse transcriptase (RT) M184I/V mutation, which is associated with resistance to lamivudine and emtricitabine [Boucher et al, 1993;Schinazi et al, 1993], on samples from patients receiving two-, three-or four-drug ART regimens.…”

Section: Introductionmentioning

confidence: 99%

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Selection of drug‐resistant HIV‐1 during the early phase of viral decay is uncommon in treatment‐naïve patients initiated on a three‐ or four‐drug antiretroviral regimen including lamivudine

Bergroth¹,

Ekici²,

Gisslén³

et al. 2008

Journal of Medical Virology

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Therapy failure due to drug resistance development is a common phenomenon in HIV-infected patients. However, when the drug pressure leads to the earliest selection of drug-resistant HIV-1 populations is still unclear. In this study, the extent to which selection of the HIV-1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment-naïve HIV-1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment-naïve patients initiating quadruple (n ¼ 43), triple (n ¼ 14) or dual (n ¼ 15) lamivudine-containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real-time PCR method. Among quadruple ART patients, who all were treated at primary HIV-1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild-type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or fourdrug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine þ PI or PI/r containing ART given to treatment-naïve adherent patients is potent enough to prevent development of resistance during the first months of therapy.

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Section: Preparation Of Patient Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selection of drug‐resistant HIV‐1 during the early phase of viral decay is uncommon in treatment‐naïve patients initiated on a three‐ or four‐drug antiretroviral regimen including lamivudine

Bergroth¹,

Ekici²,

Gisslén³

et al. 2008

Journal of Medical Virology

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“…17,18 All viral populations in a lower proportion than 20% are defined as minority population herein. Although resistant minority populations were detected in different clinical settings [12][13][14][19][20][21][22] their relevance for therapy is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure

Balduin

Oette

Däumer³

et al. 2009

Journal of Clinical Virology

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“…Unfortunately, many studies have shown that at least transient drug resistance develops in a large fraction of women after sdNVP, and drug-resistant HIV variants persist for considerable periods in patient samples at frequencies below the limit of detection of the most commonly used commercial genotyping methods. [15][16][17][18]26,27 The clinical importance of such drug-resistant ''minor variants'' following sdNVP remains unclear. Recent reports in settings other than sdNVP for PMTCT have suggested that minor variants may contribute to virologic failure.…”

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confidence: 99%

Ultrasensitive Detection of Minor Drug-Resistant Variants for HIV After Nevirapine Exposure Using Allele-Specific PCR: Clinical Significance

Rowley

Boutwell²,

Lee³

et al. 2010

AIDS Research and Human Retroviruses

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HIV-1 drug resistance mutations have been detected at low frequencies after single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT). We investigated the relationship between these ''minor variant'' NVP-resistant viruses and clinical outcome with NVP-containing antiretroviral therapy (ART). An allele-specific quantitative PCR (ASPCR) assay was used to quantify the pre-ART frequency of K103N and Y181C in 26 women who had received sdNVP. The cohort was composed of 7 patients who experienced virologic failure and 19 control patients who maintained virologic suppression on NVP-containing ART; all were negative for resistance by standard genotyping. NVP resistance mutations were found in 17 of 26 (65%) patients using ASPCR. The frequency of NVP-resistant viruses ranged from 0.1% to 4.11%. Receiver operating characteristics (ROC) analysis identified a clinical threshold frequency of 0.19% for the ASPCR assay. Application of this threshold demonstrated minor variant resistance in 6 of 7 patients (86%) who failed treatment compared to 6 of 19 patients (32%) who were successful (OR ¼ 13; 95% CI 1.27-133). ASPCR provides a means of detecting minor variant drug-resistant viruses that may impact subsequent treatment response. These data suggest a clinical role for highly sensitive assays to detect and quantify resistant viruses at low frequencies.

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Discrimination of lamivudine resistant minor HIV-1 variants by selective real-time PCR

Cited by 13 publications

References 15 publications

Selection of drug‐resistant HIV‐1 during the early phase of viral decay is uncommon in treatment‐naïve patients initiated on a three‐ or four‐drug antiretroviral regimen including lamivudine

Selection of drug‐resistant HIV‐1 during the early phase of viral decay is uncommon in treatment‐naïve patients initiated on a three‐ or four‐drug antiretroviral regimen including lamivudine

Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure

Ultrasensitive Detection of Minor Drug-Resistant Variants for HIV After Nevirapine Exposure Using Allele-Specific PCR: Clinical Significance

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