Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA for the detection of drug resistance prior to starting first-line antiretroviral therapy with etravirine or efavirenz

Geretti, Anna María; Conibear, Tim; Hill, Andrew; Johnson, Jeffrey A.; Tambuyzer, Lotke; Thys, Kim; Vingerhoets, Johan; Delft, Yvon van; Rieger, Armin; Vetter, N; Greil, Richard; Pedersen, Court; Storgaard, Merete; Morlat, Philippe; Katlama, Christine; Durant, J.; Cotte, Laurent; Duvivier, Claudine; Rey, David; Esser, Stephan; Stellbrink, C.; Schmidt, Warren N.; Stoll, Matthias; Stephan, C.; Fätkenheuer, Gerd; Stoehr, Albrecht; Rockstroh, Jürgen K.; Bánhegyi, Dénes; Itzchak, L.; Shahar, Eduardo; Maayan, Shlomo; Turner, Dan; Lazzarin, Adriano; Antinori, Andrea; Carosi, G.; Minoli, L.; Perri, Giovanni Di; Filice, G.; Andreoni, Massimo; Duiculescu, Dan; Rugină, Sorin; Erscoiu, Simona; Streinu, A.; Пронин, А В; Pokrovsky, Vadim; Gruzdev, B M; Yakovlev, Alexey N.; Voronin, Evgeny; Clotet, B; Gatell, Josep M.; Arribas, José Ramón; Podzamczer, Daniel; Domingo, Peré; Álvarez, Cristina; Quero, José Hernández; Furrer, Hansjakob; Feher, J.; Ma, Jun; Fox, Jacob H.; Nelson, Mark; Fisher, Martin; Orkin, Chloe

doi:10.1093/jac/dkt474

Cited by 23 publications

(14 citation statements)

References 42 publications

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“…This analysis was based on laboratory results from standard genotypic testing using Sanger sequencing; more sensitive assays examining low‐frequency drug‐resistance mutations were not available. Some studies have demonstrated a higher prevalence of TDR in treatment‐naïve populations using more sensitive resistance detection assays, such as ultra‐deep sequencing and allele‐specific polymerase chain reaction (PCR) . Given the limitations of genotype assays used in this analysis, the actual prevalence of TDR in the START study population is probably greater than what has been reported here.…”

Section: Discussionmentioning

confidence: 65%

Global HIV‐1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

et al. 2015

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Introduction HIV-1 transmitted drug resistance (TDR) in treatment-naïve individuals is a well-described phenomenon. Baseline genotypic resistance testing is considered standard of care in most developed areas of the world. Methods In the Strategic Timing of AntiRetroviral Treatment (START) trial, baseline genotypic resistance testing results were collected at study entry and analysed centrally to determine the prevalence of TDR in the study population. Resistance was based on a modified 2009 World Health Organization definition to reflect newer resistance mutations. Results Baseline resistance testing was available in 1946 study participants. Higher rates of testing occurred in Europe (86.7%), the United States (81.3%), and Australia (89.9%) as compared to Asia (22.2%), South America (1.8%), and Africa (0.1%). The overall prevalence of TDR was 10.1%, most commonly to non-nucleoside reverse transcriptase inhibitors (4.5%) and nucleoside reverse transcriptase inhibitors (4%) compared to protease inhibitors (2.8%). The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease. By country, prevalence of TDR was highest in Australia (17.5%), France (16.7%), the United States (12.6%), and Spain (12.6%). No participant characteristics were identified as predictors for the presence of TDR. Conclusion START participants enrolled in resource-rich areas of the world were more likely to have baseline resistance testing. In Europe, the United States, and Australia, TDR prevalence rates varied by country.

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Section: Discussionmentioning

confidence: 65%

Global HIV‐1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

et al. 2015

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“…The HIV-1 subtype was determined using polymerase sequences obtained from HIV-1 DNA recovered from PBMC, as previously described ( Geretti et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

et al. 2015

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BackgroundCharacterising the correlates of HIV persistence improves understanding of disease pathogenesis and guides the design of curative strategies. This study investigated factors associated with integrated HIV-1 DNA load during consistently suppressive first-line antiretroviral therapy (ART).MethodTotal, integrated, and 2-long terminal repeats (LTR) circular HIV-1 DNA, residual plasma HIV-1 RNA, T-cell activation markers, and soluble CD14 (sCD14) were measured in peripheral blood of 50 patients that had received 1–14 years of efavirenz-based or nevirapine-based therapy.ResultsIntegrated HIV-1 DNA load (per 106 peripheral blood mononuclear cells) was median 1.9 log10 copies (interquartile range 1.7–2.2) and showed a mean difference of 0.2 log10 copies per 10 years of suppressive ART (95% confidence interval − 0.2, 0.6; p = 0.28). It was positively correlated with total HIV-1 DNA load and frequency of CD8+HLA-DR/DP/DQ+ cells, and was also higher in subjects with higher sCD14 levels, but showed no correlation with levels of 2-LTR circular HIV-1 DNA and residual plasma HIV-1 RNA, or the frequency of CD4+CD38+ and CD8+CD38+ cells. Adjusting for pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, and sCD14 levels, integrated HIV-1 DNA load was mean 0.5 log10 copies higher for each 50% higher frequency of CD8+HLA-DR/DP/DQ+ cells (95% confidence interval 0.2, 0.9; p = 0.01).ConclusionsThe observed positive association between integrated HIV-1 DNA load and frequency of CD8+DR/DP/DQ+ cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.

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“…Most of these studies used the 454™ platform [106, 158, 159, 163, 164], but recently other deep sequencing technologies such as Illumina® [165] and Ion Torrent™ [162, 166] have proved to be useful in the identification of low-level drug resistant HIV variants. Deep sequencing has been used in HIV drug resistance surveillance [167, 168], to study transmission of HIV drug resistant viruses [101, 160, 169–175], and to evaluate the impact of minority variants on treatment efficacy [160, 176–183]. …”

Section: Deep Sequencing In the Clinical Settingmentioning

confidence: 99%

Deep sequencing: Becoming a critical tool in clinical virology

Quiñones‐Mateu¹,

Ávila²,

Reyes‐Terán³

et al. 2014

Journal of Clinical Virology

115

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Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus.

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Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA for the detection of drug resistance prior to starting first-line antiretroviral therapy with etravirine or efavirenz

Abstract: The detection of resistance increased marginally with PBMC testing but did not increase with sensitive plasma testing. A careful consideration is required of the cost-effectiveness of different strategies for baseline HIV drug resistance testing.

Cited by 23 publications

References 42 publications

Global HIV‐1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

Global HIV‐1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

Deep sequencing: Becoming a critical tool in clinical virology

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