Heterogeneity and penetration of HIV-1 non-subtype B viruses in an Italian province: public health implications

2010 ◽  
Vol 138 (9) ◽  
pp. 1298-1307 ◽  
Author(s):  
C. TORTI ◽  
G. LAPADULA ◽  
I. IZZO ◽  
G. BRINDICCI ◽  
G. LABBATE ◽  
...  
Keyword(s):  
Resistance Testing ◽  
Targeted Prevention ◽  
South American ◽  
Genotypic Resistance ◽  
Subtype B ◽  
Genotypic Resistance Testing ◽  
B Virus ◽  
G 12 ◽  
Hiv Acquisition ◽  
Hiv 1

SUMMARYThis study assessed changes in prevalence and distribution of HIV-1 non-subtype B viruses in Italian and immigrant patients over two decades in a province in Italy. All HIV-positive patients who underwent genotypic resistance testing were selected. Prevalence of non-subtype B viruses in 3-year periods was calculated. All sequences of non-subtype B and those provided by REGA as unassigned were analysed for phylogenetic relationships. In total, 250/1563 (16%) individuals were infected with a non-subtype B virus. Prevalence increased over time, reaching a peak (31·5%) in 2004–2006. In Italian patients, the most frequent subtypes were B (92·5%) and F1 (4%). F1 subtype was also prevalent in patients from South America (13·6%); in patients of African origin, CRF02_AG (54·9%) and G (12·3%) were the most frequent. HIV-1 non-subtype B infections in Italians were mostly found in patients who acquired HIV sexually. A phylogenetic relationship between F subtypes in Italian and representative HIV-1 sequences from Brazil was found. C subtypes in Italians were phylogenetically related to subtypes circulating in Brazil. Inter-subtype recombinants were also found in the latest years. The HIV-1 epidemic in Brescia province evolved to the point where about 1/3 patients recently diagnosed harboured non-B HIV subtypes. The distribution of HIV-1 non-B subtypes in Italian patients resembled that in South American patients and phylogenetic relatedness between some Italian and South American HIV-1 strains was found. The possible epidemiological link between these two populations would have been missed by looking only at risk factors for HIV acquisition declared by patients. The evidence of inter-subtype recombinants points to significant genetic assortment. Overall our results support phylogenetic analysis as a tool for epidemiological investigation in order to guide targeted prevention strategies.

scholarly journals HIV-1 Protease, Reverse Transcriptase, and Integrase Variation

2016 ◽  
Vol 90 (13) ◽  
pp. 6058-6070 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Kris Sankaran ◽  
Vici Varghese ◽  
Mark A. Winters ◽  
Christopher B. Hurt ◽  
...  
Keyword(s):  
Quality Control ◽  
Amino Acid ◽  
Amino Acid Position ◽  
Antiretroviral Drugs ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Naturally Occurring ◽  
Genotypic Resistance Testing ◽  
Hiv 1 ◽  
Amino Acid Variants

ABSTRACTHIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-generation sequencing (NGS) to detect low-abundance HIV-1 variants. We analyzed PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to characterize variation at each amino acid position, identify mutations indicating APOBEC-mediated G-to-A editing, and identify mutations resulting from selective drug pressure. Forty-seven percent of PR, 37% of RT, and 34% of IN positions had one or more amino acid variants with a prevalence of ≥1%. Seventy percent of PR, 60% of RT, and 60% of IN positions had one or more variants with a prevalence of ≥0.1%. Overall 201 PR, 636 RT, and 346 IN variants had a prevalence of ≥0.1%. The median intersubtype prevalence ratios were 2.9-, 2.1-, and 1.9-fold for these PR, RT, and IN variants, respectively. Only 5.0% of PR, 3.7% of RT, and 2.0% of IN variants had a median intersubtype prevalence ratio of ≥10-fold. Variants at lower prevalences were more likely to differ biochemically and to be part of an electrophoretic mixture compared to high-prevalence variants. There were 209 mutations indicative of APOBEC-mediated G-to-A editing and 326 mutations nonpolymorphic treatment selected. Identification of viruses with a high number of APOBEC-associated mutations will facilitate the quality control of dried blood spot sequencing. Identifying sequences with a high proportion of rare mutations will facilitate the quality control of NGS.IMPORTANCEMost antiretroviral drugs target three HIV-1 proteins: PR, RT, and IN. These proteins are highly variable: many different amino acids can be present at the same position in viruses from different individuals. Some of the amino acid variants cause drug resistance and occur mainly in individuals receiving antiretroviral drugs. Some variants result from a human cellular defense mechanism called APOBEC-mediated hypermutation. Many variants result from naturally occurring mutation. Some variants may represent technical artifacts. We studied PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to quantify variation at each amino acid position in these three HIV-1 proteins. We performed analyses to determine which amino acid variants resulted from antiretroviral drug selection pressure, APOBEC-mediated editing, and naturally occurring variation. Our results provide information essential to clinical, research, and public health laboratories performing genotypic resistance testing by sequencing HIV-1 PR, RT, and IN.

Evaluation of HIV-1 and CD4+ T Cell Dynamic Parameters in Patients Treated with Genotypic Resistance Testing-Guided HAART

2008 ◽  
Vol 6 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Antonio Cappuccio ◽  
Filippo Castiglione ◽  
Benedetto Piccoli ◽  
Valerio Tozzi
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Resistance Testing ◽  
Dynamic Parameters ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing ◽  
Hiv 1

scholarly journals HIV-1 Genotypic Resistance Testing on Low Viral Load Specimens Using the Abbott ViroSeq HIV-1 Genotyping System

2008 ◽  
Vol 39 (11) ◽  
pp. 671-673 ◽  
Author(s):  
Zhen Yang ◽  
Richard Morrison ◽  
Carl Oates ◽  
Juan Sarria ◽  
Janak Patel ◽  
...  
Keyword(s):  
Viral Load ◽  
Resistance Testing ◽  
Genotypic Resistance ◽  
Genotypic Resistance Testing ◽  
Hiv 1

scholarly journals Genetic Consequences of Antiviral Therapy on HIV-1

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Miguel Arenas
Keyword(s):  
Enzyme Inhibitors ◽  
Resistance Testing ◽  
Evolutionary Analysis ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Antiviral Therapies ◽  
Genotypic Resistance Testing ◽  
Before And After ◽  
Emergence Of Resistance ◽  
Hiv 1

A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the viral genetic diversity and molecular adaptation. The role of recombination in the generation of drug resistance is also analyzed. Besides the investigation and discussion of published works, an evolutionary analysis of protease-coding genes collected from patients before and after treatment with different protease inhibitors was included to validate previous studies. Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments design.

scholarly journals HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0145772 ◽  
Author(s):  
Soo-Yon Rhee ◽  
Michael R. Jordan ◽  
Elliot Raizes ◽  
Arlene Chua ◽  
Neil Parkin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Point Of Care ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Drug Resistance Mutations ◽  
Genotypic Resistance Testing ◽  
Potential Applications ◽  
Hiv 1

scholarly journals A2 Phylogenetic investigation of transmitted HIV-1 drug resistance mutations in Denmark, 2009–17

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
J Fonager ◽  
T K Fischer
Keyword(s):  
Drug Resistance ◽  
Resistance Testing ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Sequence Alignments ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Genotypic Resistance Testing ◽  
Hiv 1

Abstract Transmission of HIV-1 resistance mutations among therapy-naïve patients impairs the efficiency of antiretroviral therapy (ART). Therefore, genotypic resistance testing of patients is recommended at baseline, as this both allows for the selection of the correct ART regimen and for surveillance of transmitted drug resistance mutations (TDRM) among therapy naive HIV-1 patients. In Denmark, the occurrence of TDRM in newly diagnosed and therapy naïve HIV-1 patients is monitored through the SERO project. Here, we investigated if the prevalence of TDRM differed between patients within and outside of phylogenetically identified transmission clusters. Samples from 1,227 newly diagnosed HIV-1 patients were sent along with epidemiological information to the Virological Surveillance and Research group at Statens Serum Institut. HIV-1 RNA extraction, RT-PCR and Sanger sequencing of the pol gene was performed using an in-house assay. The sequences were analyzed using BioNumerics v. 6.6 and manually checked for the presence of mixed mutations and analyzed for mutations using the HIVDB 8.4 algorithm implemented at the Stanford database. Sequence alignments were performed in Mafft, and phylogenetic analysis was performed using Mega 6.0 using the Maximum likelihood general time reversible model with 100 bootstrap replicates. Clusters were identified with ClusterPicker at default settings (cluster support = 90%, genetic distance 4.5%). Active clusters contained newly diagnosed patients from the 2015 to 2017 period. HIV-1 sequences from 588 patients belonged to one of 154 clusters, and sequences from 639 patients did not belong to a cluster. Patients in clusters were significantly more likely to be men who have sex with men and subtype B and significantly less likely to be late presenters (Fisher’s test P < 0.05). The TDRM prevalence was significantly higher for patients outside of clusters than within clusters, 16.6 per cent versus 12.1 per cent, respectively (Fisher’s test P < 0.05); however, no significant differences were found in the TDRM prevalence between the 75 active and 79 inactive clusters, nor between small (<3 patients) and large (≥3 patients) clusters. E138A, V179D, and K103N were the three most prevalent TDRMs for both patient groups, whereas M41L differed between them. In Denmark, the TDRM prevalence is lower within clusters than outside, indicating that TDRM cases are either imported and/or belong to yet unidentified clusters.

Sign in / Sign up

Export Citation Format

Share Document