scholarly journals Characterization of HIV-1 near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

2017 ◽  
Author(s):  
Brunna M. Alves ◽  
Juliana D. Siqueira ◽  
Marianne M. Garrido ◽  
Ornella M. Botelho ◽  
Isabel M. Prellwitz ◽  
...  
Keyword(s):  
Viral Load ◽  
Highly Active Antiretroviral Therapy ◽  
Treatment Success ◽  
Undetectable Viral Load ◽  
Hiv Treatment ◽  
Full Length ◽  
Resistance Mutations ◽  
First Line ◽  
Subtype B ◽  
Hiv 1

Increased access to highly active antiretroviral therapy (HAART) by HIV+ individuals has become a reality worldwide. In Brazil, ART currently reaches over half of the HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. For this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

scholarly journals Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

Viruses ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 392 ◽  
Author(s):  
Brunna Alves ◽  
Juliana Siqueira ◽  
Marianne Garrido ◽  
Ornella Botelho ◽  
Isabel Prellwitz ◽  
...  
Keyword(s):  
Viral Load ◽  
Undetectable Viral Load ◽  
Full Length ◽  
Proviral Genome ◽  
First Line ◽  
Hiv 1 ◽  
Haart Therapy

scholarly journals Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Juan Pablo Rodriguez-Auad ◽  
Othon Rojas-Montes ◽  
Angelica Maldonado-Rodriguez ◽  
Ma. Teresa Alvarez-Muñoz ◽  
Onofre Muñoz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Attractive Alternative ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Resource Limited Settings ◽  
Middle Income ◽  
Subtype B ◽  
Resource Limited ◽  
Hiv 1

Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10copies/mL in liquid plasma and 4.1 log10copies/mL in DPS, with a correlation coefficient ofR= 0.83. A 1.1 kb fragment of HIVpolcould be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1polsequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

Different Kinetics of Immunologic Recovery Using Nelfinavir or Lopinavir/Ritonavir-Based Regimens in Children with Perinatal HIV-1 Infection

2005 ◽  
Vol 18 (4) ◽  
pp. 729-735 ◽  
Author(s):  
M. De Luca ◽  
G. Miccinesi ◽  
E. Chiappini ◽  
M. Zappa ◽  
L. Galli ◽  
...  
Keyword(s):  
Viral Load ◽  
T Lymphocyte ◽  
Highly Active Antiretroviral Therapy ◽  
Lymphocyte Count ◽  
Virologic Failure ◽  
Undetectable Viral Load ◽  
Baseline Viral Load ◽  
Perinatal Hiv ◽  
Significant Difference ◽  
Hiv 1

The choice to include the optimal protease inhibitor (PI) in highly active antiretroviral therapy (HAART) regimens in children with perinatal HIV-1 infection is still under debate. Virologic and immunologic outcomes of three different regimens in an observational paediatric cohort were compared. Data from 12 saquinavir-, 18 nelfinavir-, and 10 lopinavir/ritonavir-treated children were analyzed after 4 and 24 weeks of therapy. Immunologic and virologic outcomes were compared using multivariate analysis adjusting the results for age, baseline CD4+ T-lymphocyte count and baseline viral load. Saquinavir-treated children displayed significant reduction in viral load at week 24 (but not at week 4) and no increase in CD4+ T-lymphocyte count, indicating a poor advantage in using this drug. Lopinavir/ritonavir-treated children presented lower viral loads than nelfinavir-treated children at week 4 (P=0.020) and week 24 (p<0.0001). Virologic failure occurred in 6/18 (33.3%) nelfinavir-treated children but in no child receiving lopinavir/ritonavir (P=0.013). An undetectable viral load was achieved in 9/10 (90.0%) lopinavir/ritonavir- vs. 3/18 (16.6%) nelfinavir-treated children (p<0.0001). No significant difference in CD4+ T-lymphocyte count was observed between lopinavir/ritonavir- and nelfinavir-treated children at weeks 4 and 24. However, a different kinetic of the immunologic recovery was observed. Lopinavir/ritonavir-treated children displayed higher CD4+ T-lymphocyte counts than saquinavir-treated children since the first month of therapy (week 4: P=0.042; week 24: P= 0.029) while nelfinavir-treated children took 24 weeks to reach such an outcome (P=0.034). Since lopinavir/ritonavir-based regimen controls viral replication more efficiently and restores CD4+ T-lymphocyte count more quickly than saquinavir- or nelfinavir-based HAART, it may be considered when a salvage therapy or a rapid increase in CD4+ T-lymphocytes is necessary.

An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy

2019 ◽  
Vol 74 (10) ◽  
pp. 3011-3015 ◽  
Author(s):  
Anna Maria Geretti ◽  
Adam Abdullahi ◽  
Olga Mafotsing Fopoussi ◽  
Laura Bonnett ◽  
Victoire Fokom Defo ◽  
...  
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Dna Sequences ◽  
Sub Saharan Africa ◽  
Resistance Mutations ◽  
First Line ◽  
Second Line Therapy ◽  
Apparent Paradox ◽  
Sub Saharan ◽  
Hiv 1

Abstract Background In sub-Saharan Africa, detecting resistance-associated mutations (RAMs) at failure of first-line ART with two NRTIs plus an NNRTI predicts improved virological responses to second-line therapy with two NRTIs plus a ritonavir-boosted PI (PI/r). This indicates residual NRTI activity in the presence of RAMs, although additional factors may contribute to the effect. Objectives The aim of this study was to investigate the influence of pre-existing RAMs on the outcomes of maintenance monotherapy with ritonavir-boosted darunavir within a randomized trial in Cameroon. Methods RAMs were detected in HIV-1 DNA using PBMCs collected at initiation of darunavir/ritonavir monotherapy. Adherence was assessed by pill count and visual analogue scale (VAS). Predictors of virological failure (confirmed or last available viral load >400 copies/mL) were explored by logistic regression analysis. Trial name = MANET (NCT02155101). Results After NNRTI-based therapy, participants (n = 81) had received PI/r-based therapy for a median of 3.2 years and had a confirmed viral load <60 copies/mL and a median CD4 count of 466 cells/mm3. NRTI and NNRTI RAMs were detected in 39/60 (65.0%) and 41/60 (68.3%) HIV-1 DNA sequences, respectively. Over 48 weeks of monotherapy, 16/81 (19.8%) patients experienced virological failure. After adjusting for age, HIV-1 DNA load, adherence by VAS and RAM status, virological failure was less likely with higher VAS-measured adherence (adjusted OR 0.04, 95% CI 0.01–0.37; P = 0.004) and detectable HIV-1 DNA RAMs (adjusted OR 0.15, 95% CI 0.03–0.82; P = 0.028). Conclusions Pre-existing NRTI and NNRTI RAMs are associated with improved virological responses to NRTI-sparing ART in sub-Saharan Africa, indicating a predictive effect that is independent of residual NRTI activity.

scholarly journals Secondary Integrase Resistance Mutations Found in HIV-1 Minority Quasispecies in Integrase Therapy-Naive Patients Have Little or No Effect on Susceptibility to Integrase Inhibitors

2010 ◽  
Vol 54 (9) ◽  
pp. 3938-3948 ◽  
Author(s):  
Francesca Ceccherini-Silberstein ◽  
Kurt Van Baelen ◽  
Daniele Armenia ◽  
Maria Trignetti ◽  
Evelien Rondelez ◽  
...  
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Novel Mutation ◽  
Rnase H ◽  
Replication Capacity ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Recombinant Viruses ◽  
Subtype B ◽  
Hiv 1

ABSTRACTThe goal of this study was to explore the presence of integrase strand transfer inhibitor (InSTI) resistance mutations in HIV-1 quasispecies present in InSTI-naïve patients and to evaluate theirin vitroeffects on phenotypic susceptibility to InSTIs and their replication capacities. The RT-RNase H-IN region was PCR amplified from plasma viral RNA obtained from 49 HIV-1 subtype B-infected patients (21 drug naïve and 28 failing highly active antiretroviral therapy [HAART] not containing InSTIs) and recombined with an HXB2-based backbone with RT and IN deleted. Recombinant viruses were tested against raltegravir and elvitegravir and for replication capacity. Three-hundred forty-four recombinant viruses from 49 patients were successfully analyzed both phenotypically and genotypically. The majority of clones were not phenotypically resistant to InSTIs: 0/344 clones showed raltegravir resistance, and only 3 (0.87%) showed low-level elvitegravir resistance. No primary resistance mutations for raltegravir and elvitegravir were found as major or minor species. The majority of secondary mutations were also absent or rarely present. Secondary mutations, such as T97A and G140S, found rarely and only as minority quasispecies, were present in the elvitegravir-resistant clones. A novel mutation, E92G, although rarely found in minority quasispecies, showed elvitegravir resistance. Preexisting genotypic and phenotypic raltegravir resistance was extremely rare in InSTI-naïve patients and confined to only a restricted minority of secondary variants. Overall, these results, together with others based on population and ultradeep sequencing, suggest that at this point IN genotyping in all patients before raltegravir treatment may not be cost-effective and should not be recommended until evidence of transmitted drug resistance to InSTIs or the clinical relevance of IN minor variants/polymorphisms is determined.

scholarly journals The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Carmen Andréa F. Lopes ◽  
Marcelo A. Soares ◽  
Diego R. Falci ◽  
Eduardo Sprinz
Keyword(s):  
Antiretroviral Treatment ◽  
Drug Regimen ◽  
Hiv Treatment ◽  
Resistance Mutations ◽  
Hiv Resistance ◽  
The North ◽  
Subtype B ◽  
Northern Brazil ◽  
First Time ◽  
Hiv 1

HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

scholarly journals Decreased Specificity of an Assay for Recent Infection in HIV-1-Infected Patients on Highly Active Antiretroviral Treatment: Implications for Incidence Estimates

2012 ◽  
Vol 19 (8) ◽  
pp. 1248-1253 ◽  
Author(s):  
Antoine Chaillon ◽  
Stéphane Le Vu ◽  
Sylvie Brunet ◽  
Guillaume Gras ◽  
Frédéric Bastides ◽  
...  
Keyword(s):  
Viral Load ◽  
Highly Active Antiretroviral Therapy ◽  
Demographic Data ◽  
Undetectable Viral Load ◽  
Antiretroviral Drugs ◽  
Recent Infection ◽  
Cross Sectional ◽  
Highly Active ◽  
The Impact ◽  
Hiv 1

ABSTRACTThe aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4+T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%,P< 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations.

Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China

2020 ◽  
Vol 18 (3) ◽  
pp. 210-218
Author(s):  
Guolong Yu ◽  
Yan Li ◽  
Xuhe Huang ◽  
Pingping Zhou ◽  
Jin Yan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Phylogenetic Analyses ◽  
Resistance Mutations ◽  
Protease Inhibition ◽  
Subtype B ◽  
Primary Drug Resistance ◽  
Hiv 1 ◽  
Primary Drug

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

scholarly journals Analysis of Low-Frequency Mutations Associated with Drug Resistance to Raltegravir before Antiretroviral Treatment

2010 ◽  
Vol 55 (3) ◽  
pp. 1114-1119 ◽  
Author(s):  
Jia Liu ◽  
Michael D. Miller ◽  
Robert M. Danovich ◽  
Nathan Vandergrift ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Low Frequency ◽  
Hiv Treatment ◽  
Viral Population ◽  
Virologic Suppression ◽  
Resistance Mutations ◽  
The Difference ◽  
Allele Specific Sequencing ◽  
Hiv 1

ABSTRACTRaltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients,n= 36) and those who experienced virologic rebound (failure patients,n= 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.

Sign in / Sign up

Export Citation Format

Share Document