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Find video protocols related to scientific articles indexed in Pubmed.
Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.
PLoS ONE
PUBLISHED: 01-01-2014
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Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs) is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS) before antiretroviral therapy (ART) and at virological failure (VF), in HIV-1 infected patients experiencing VF on first-line ART.
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A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure.
Int. J. Antimicrob. Agents
PUBLISHED: 01-20-2013
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This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ? 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ? 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ? 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.
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Virologic and immunologic response to cART by HIV-1 subtype in the CASCADE collaboration.
PLoS ONE
PUBLISHED: 01-01-2013
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We aimed to compare rates of virologic response and CD4 changes after combination antiretroviral (cART) initiation in individuals infected with B and specific non-B HIV subtypes.
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Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study.
Lancet Infect Dis
PUBLISHED: 10-09-2011
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Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09.
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Docking analysis and resistance evaluation of clinically relevant mutations associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors nevirapine, efavirenz and etravirine.
ChemMedChem
PUBLISHED: 07-25-2011
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An integrated computational and statistical approach was used to determine the association of non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine, efavirenz and etravirine with resistance mutations that cause therapeutic failure and their impact on NNRTI resistance. Mutations detected for nevirapine virological failure with a prevalence greater than 10% in the used patient set were: K103N, Y181C, G190A, and K101E. A support vector regression model, based on matched genotypic/phenotypic data (n=850), showed that among 6365 analyzed mutations, K103N, Y181C and G190A have the first, third, and sixth greatest significance for nevirapine resistance, respectively. The most common indicator of treatment failure for efavirenz was K103N mutation present in 56.7% of the patients where the drug failed, followed by V108I, L100I, and G190A. For efavirenz resistance, K103N, G190, and L100I have the first, fourth, and eighth greatest significance, respectively, as determined in support vector regression model. No positive interactions were observed among nevirapine resistance mutations, while a more complex situation was observed with treatment failure of efavirenz and etravirine, characterized by the accumulation of multiple mutations. Docking simulations and free energy analysis based on docking scores of mutated human immunodeficiency virus (HIV) RT complexes were used to evaluate the influence of selected mutations on drug recognition. Results from support vector regression were confirmed by docking analysis. In particular, for nevirapine and efavirenz, a single mutation K103N was associated with the most unfavorable energetic profile compared to the wild-type sequence. This is in line with recent clinical data reporting that diarylpyrimidine etravirine, a very potent third generation drug effective against a wide range of drug-resistant HIV-1 variants, shows increased affinity towards K103N/S mutants due to its high conformational flexibility.
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Improved V3 genotyping with duplicate PCR amplification for determining HIV-1 tropism.
J. Antimicrob. Chemother.
PUBLISHED: 06-14-2011
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To determine whether genotyping of HIV-1 by duplicate PCR amplification of the region encoding the V3 loop is more sensitive than single PCR for detecting CXCR4-using viruses.
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High prevalence of antiretroviral drug resistance among HIV-1-untreated patients in Guinea-Conakry and in Niger.
Antivir. Ther. (Lond.)
PUBLISHED: 05-11-2011
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The aim of the study was to assess the prevalence of antiretroviral drug resistance mutations in HIV-1 from recently diagnosed and untreated patients living in Conakry, Guinea-Conakry and in Niamey, Niger.
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Cellular HIV-1 DNA quantification and short-term and long-term response to antiretroviral therapy.
J. Antimicrob. Chemother.
PUBLISHED: 04-27-2011
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The aim of our study was to determine whether HIV-1 DNA level before antiretroviral therapy (ART) was associated with short- and long-term virological and immunological responses.
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Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients.
J. Antimicrob. Chemother.
PUBLISHED: 04-07-2011
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To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients.
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Low-frequency HIV-1 drug resistance mutations and risk of NNRTI-based antiretroviral treatment failure: a systematic review and pooled analysis.
JAMA
PUBLISHED: 04-07-2011
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Presence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting.
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Concordance between two phenotypic assays and ultradeep pyrosequencing for determining HIV-1 tropism.
Antimicrob. Agents Chemother.
PUBLISHED: 04-04-2011
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There have been few studies on the concordance between phenotypic assays for predicting human immunodeficiency virus type 1 (HIV-1) coreceptor usage. The sensitivity of ultradeep pyrosequencing combined with genotyping tools is similar to that of phenotypic assays for detecting minor CXCR4-using variants. We evaluated the agreement between two phenotypic assays, the Toulouse tropism test (TTT) and the Trofile assay, and ultradeep pyrosequencing for determining the tropism of HIV-1 quasispecies. The concordance between the TTT and Trofile assays was assessed for 181 samples successfully phenotyped by both assays. The TTT was 86% concordant with the standard Trofile assay and 91.7% with its enhanced-sensitivity version. The concordance between phenotypic characterization of HIV-1 tropism and ultradeep pyrosequencing genotypic prediction was further studied in selected samples. The HIV-1 tropism inferred from ultradeep pyrosequencing of 11 samples phenotyped as X4 and dualtropic and 12 phenotyped as R5-tropic agreed closely with the results of phenotyping. However, ultradeep pyrosequencing detected minor CXCR4-using variants in 3 of 12 samples phenotyped as R5-tropic. Ultradeep pyrosequencing also detected minor CXCR4-using variants that had been missed by direct sequencing in 6 of 9 samples phenotyped as X4-tropic but genotyped as R5-tropic by direct sequencing. Ultradeep pyrosequencing was 87% concordant with the Trofile and TTT phenotypic assays and was in the same range of sensitivity (0.4%) than these two phenotypic assays (0.3 to 0.5%) for detecting minor CXCR4-using variants. Ultradeep pyrosequencing provides a new way to improve the performance of genotypic prediction of HIV-1 tropism to match that of the phenotypic assays.
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Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.
Antimicrob. Agents Chemother.
PUBLISHED: 06-07-2010
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Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.
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HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens.
J. Antimicrob. Chemother.
PUBLISHED: 04-12-2010
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Our aim was to study the in vivo viral genetic pathways for resistance to raltegravir, in antiretroviral-experienced patients with virological failure (VF) on raltegravir-containing regimens.
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The HIV-1 integrase mutations Y143C/R are an alternative pathway for resistance to Raltegravir and impact the enzyme functions.
PLoS ONE
PUBLISHED: 03-28-2010
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Resistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3end-processing, strand transfer and concerted integration assays. Activities of mutants were moderately impaired for 3end-processing and severely affected for strand transfer. Concerted integration assay demonstrated a decrease in mutant activities using an uncleaved substrate. With 3end-processing assay, IC(50) were 0.4 microM, 0.9 microM (FC = 2.25) and 1.2 microM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. An FC of 2 was observed only for IN Y143R in the strand transfer assay. In concerted integration, integrases were less sensitive to RAL than in ST or 3P but mutants were more resistant to RAL than WT.
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Evolution of 2-long terminal repeat (2-LTR) episomal HIV-1 DNA in raltegravir-treated patients and in in vitro infected cells.
J. Antimicrob. Chemother.
PUBLISHED: 01-05-2010
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Our aim was to analyse the evolution of HIV-1 2-long terminal repeat (2-LTR) circular DNA in vitro and ex vivo in the presence of raltegravir.
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Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes.
Antimicrob. Agents Chemother.
PUBLISHED: 12-14-2009
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Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02_AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02_AG than in other non-B subtypes (P=0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility.
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Surveillance of HIV type 1 drug resistance among naive patients from Venezuela.
AIDS Res. Hum. Retroviruses
PUBLISHED: 12-04-2009
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We have studied 65 HIV-1-infected untreated patients recruited in Caracas, Venezuela with TCD4 counts > or =350/microl. The reverse transcriptase and protease sequences of the virus were sequenced, aligned with reference HIV-1 group M strains, and analyzed for drug resistance mutations. Most of the viruses were subtype B genotype in both the protease and RT genomic regions. Five of the 62 virus isolates successfully amplified showed evidence of recombination between protease and RT, with their protease region being non-B while their RT region was derived from subtype B. Four strains were found bearing resistance mutations either to NRTIs, NNRTIs, or PIs. The prevalence of HIV-1 isolates bearing resistance mutations was therefore above the 5% threshold of WHO.
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Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients.
Antimicrob. Agents Chemother.
PUBLISHED: 11-09-2009
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To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log(10) copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm(3) (IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log(10) copies/ml and/or HIV-1 RNA level of <50 copies/ml. No difference in VR was observed between patients receiving or not a boosted PI in combination with ETR. Factors independently associated with a better VR to ETR were the number of drugs (among enfuvirtide, darunavir, or raltegravir) used for the first time in combination with ETR and the presence of the K103N mutation at baseline. Mutations Y181V and E138A were independently associated with poor VR, whereas no effect of the Y181C on VR was observed. In conclusion, ETR was associated with high response rates in NNRTI-experienced patients in combination with other active drugs regardless of the therapeutic class used.
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HIV type-1 transmission dynamics in recent seroconverters: relationship with transmission of drug resistance and viral diversity.
Antivir. Ther. (Lond.)
PUBLISHED: 07-07-2009
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HIV type-1 (HIV-1) has been shown to be frequently transmitted by acutely infected patients. We investigated the relationship between the dynamics of HIV-1 transmission within recently infected patients, the HIV-1 variability and the transmission of antiretroviral drug resistance.
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Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort.
J. Antimicrob. Chemother.
PUBLISHED: 03-31-2009
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The efficacy of raltegravir plus optimized background therapy (OBT) has been demonstrated for antiretroviral (ARV)-experienced HIV-1-infected patients in randomized clinical trials. We studied viro-immunological response, pharmacokinetic parameters and genotypic test results in an observational cohort of multiple ARV class-experienced patients starting a raltegravir-based regimen.
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Stable frequency of HIV-1 transmitted drug resistance in patients at the time of primary infection over 1996-2006 in France.
AIDS
PUBLISHED: 03-13-2009
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Transmission of drug-resistant variants is influenced by several factors, including the HIV-1 RNA levels in HIV-1-infected patients. Our study describes the transmitted drug-resistant virus among 1446 French patients diagnosed at the time of primary infection and included from 1996 to 2006 along with the proportion of chronically infected treated patients in the French Hospital Database on HIV (FHDH).
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Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection.
Antimicrob. Agents Chemother.
PUBLISHED: 01-26-2009
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We used an allele-specific real-time PCR assay to explore the presence of K103N and M184V minority species among primary human immunodeficiency virus (HIV) infections and their potential influence in HIV transmission. Thirty randomly chosen antiretroviral drug-naive patients lacking both the K103N and the M184V mutations as determined by conventional sequencing methods were studied, and K103N and M184V viral minority species were found in three (10%) and four (11%) patients, respectively.
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Phylogenetic reconstruction of transmission events from individuals with acute HIV infection: toward more-rigorous epidemiological definitions.
J. Infect. Dis.
PUBLISHED: 01-13-2009
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Phylogenetic reconstructions of transmission events from individuals with acute human immunodeficiency virus (HIV) infection are conducted to illustrate this groups heightened infectivity. Varied definitions of acute infection and assumptions about observed phylogenetic clusters may produce misleading results. We conducted a phylogenetic analysis of HIV pol sequences from 165 European patients with estimated infection dates and calculated the difference between dates within clusters. Nine phylogenetic clusters were observed. Comparison of dates within clusters revealed that only 2 could have been generated during acute infection. Previous analyses may have incorrectly assigned transmission events to the acutely HIV infected when they were more likely to have occurred during chronic infection.
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Similar evolution of cellular HIV-1 DNA level in darunavir/ritonavir monotherapy versus triple therapy in MONOI-ANRS136 trial over 96 weeks.
PLoS ONE
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A higher proportion of intermittent viremia (to have a HIV-1 RNA viral load>50 copies/mL not confirmed) was reported in the boosted protease inhibitor monotherapy arm in some studies including MONOI trial, and that could have an impact on the replenishment of the HIV-1 DNA reservoirs. The HIV-1 DNA level is an interesting marker which reflects the size of cellular HIV reservoir. Our objectives were to study the impact of 96 weeks of Darunavir/ritonavir monotherapy versus a triple standard combination on the HIV-1 blood reservoir and factors associated with HIV-1 plasma DNA at baseline in MONOI trial sub-study.
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Impact of lopinavir/ritonavir use on antiretroviral resistance in recent clinical practice.
J. Antimicrob. Chemother.
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This observational study was requested by French health authorities to determine the impact of lopinavir/ritonavir (Kaletra(®)) on antiretroviral resistance in clinical practice. Virological failures of lopinavir/ritonavir and their effects on the resistance to protease inhibitors and reverse transcriptase inhibitors were evaluated in protease inhibitor-experienced patients.
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Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen.
Antivir. Ther. (Lond.)
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The aim of this study was to characterize the mutations selected upon failure on etravirine (ETR)-containing regimen in non-nucleoside reverse transcriptase inhibitors (NNRTIs)-experienced HIV-infected patients and the associated factors.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.