Publications by authors named "Charlotte Charpentier"

167 Publications

Evaluation of three extraction-free SARS-CoV-2 RT-PCR assays: A feasible alternative approach with low technical requirements.

J Virol Methods 2021 Feb 9;291:114086. Epub 2021 Feb 9.

Université de Paris, INSERM UMR 1137 IAME, Laboratoire de Virologie, AP-HP, Hôpital Bichat-Claude Bernard, F-75018 Paris, France. Electronic address:

The worldwide demand for SARS-CoV-2 RT-PCR testing resulted in a shortage of diagnostic kits. RNA extraction step constitutes a major bottleneck to perform diagnostic. The aim of this study was to assess performances of different extraction-free SARS-CoV-2 RT-PCR assays compared to a reference RT-PCR assay. The panel of evaluation consisted of 94 samples: 69 positive and 25 negative for SARS-CoV-2 by reference RT-PCR. Three extraction-free RT-PCR assays were assessed: (i) PrimeDirect® Probe RT-qPCR Mix (Takara), (ii) PrimeScript®RT-PCR (Takara), and (iii) SARS-CoV-2 SANSURE®BIOTECH Novel Coronavirus (Sansure). The overall sensitivity of PrimeDirect, PrimeScript and Sansure assays was 55.1 %, 69.6 % and 69.6 %, respectively. The sensitivity increased among samples with Ct<30: 91.9 % (n = 34/37), 89.2 % (n = 33/37) and 94.6 % (n = 35/37) for PrimeDirect, PrimeScript and Sansure assays, respectively. The specificity was 88 %, 100 % and 100 % for PrimeDirect, PrimeScript and Sansure assays, respectively. In the present study, we showed a good sensitivity of extraction-free PCR assays, especially for high viral loads (Ct<30), except PrimeDirect that displayed imperfect sensitivity and specificity. Despite a lower sensitivity for low viral loads, extraction-free reagents can provide a valuable option, cheaper, easier and less reagent consuming for SARS-CoV-2 diagnostic, especially in laboratory with lower experience and equipment for molecular assays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2021.114086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871772PMC
February 2021

Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives.

Clin Microbiol Infect 2020 12 8. Epub 2020 Dec 8.

Université de Paris, IAME, INSERM, Paris, France; Virology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France. Electronic address:

Objectives: Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. The high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the clinical performances of SARS-CoV-2 nucleocapsid antigen (N-antigen) ELISA detection in serum or plasma using the COVID-19 Quantigene® (AAZ, France) assay.

Methods: Performances were determined on 63 sera from 63 non-COVID patients and 227 serum samples (165 patients) from the French COVID and CoV-CONTACT cohorts with RT-PCR confirmed SARS-CoV-2 infection, including 142 serum (114 patients) obtained within 14 days after symptoms' onset.

Results: Specificity was 98.4% (95% confidence interval [CI], 95.3 to 100). Sensitivity was 79.3% overall (180/227, 95% CI, 74.0 to 84.6) and 93.0% (132/142, 95% CI, 88.7 to 97.2) within 14 days after symptoms onset. 91 included patients had a sera and nasopharyngeal swabs collected in the same 24 hours. Among those with high nasopharyngeal viral loads, i.e. Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among those with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia; the lower respiratory tract was explored for 6 of these 8 patients, showing positive RT-PCR in 5 cases.

Conclusion: This is the first evaluation of a commercially available serum N-antigen detection assay. It presents a robust specificity and sensitivity within the first 14 days after symptoms onset. This approach provides a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmi.2020.11.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724284PMC
December 2020

PD-1/PD-L1 expression in anal squamous intraepithelial lesions.

Oncotarget 2020 Sep 29;11(39):3582-3589. Epub 2020 Sep 29.

AP-HP, Service de Gastroentérologie et Proctologie, Hôpital Bichat-Claude Bernard, F-75018 Paris, France.

Introduction: Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. The description of the expression of these molecules has never been performed in anal low-grade/high grade squamous intra-epithelial lesions (LSIL/HSIL respectively).

Materials And Methods: Patients followed in the AIN3 cohort were routinely sampled. For each selected sample, an immunohistochemical study was performed with anti-CD8, PD-1, PD-L1 antibodies. The presence and distribution of CD8+ lymphocytes, and the presence of PD-1+ lymphocytes and PD-L1+ epithelial cells were assessed. The comparison of these characteristics was performed between the HSIL and LSIL groups.

Results: 33 patients were included and 78 samples selected (60 HSIL and 18 LSIL). CD8+ lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial (respectively 90% vs. 60%, = 0.01; and 62% vs. 33%, = 0.04). PD-1+ lymphocytes were observed more frequently in HSIL versus LSIL (41% vs 11%, = 0.03). There was no difference between HSIL and LSIL for PD-L1+ epithelial cells.

Conclusions: Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions. These results highlight the involvement of the PD-1/PD-L1 pathway in the natural history of anal dysplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.27756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533075PMC
September 2020

A Comparison of Cell Activation, Exhaustion, and Expression of HIV Coreceptors and Restriction Factors in HIV-1- and HIV-2-Infected Nonprogressors.

AIDS Res Hum Retroviruses 2020 Nov 12. Epub 2020 Nov 12.

Inserm 1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Sorbonne Université, Paris, France.

Human immunodeficiency viruses induce rare attenuated diseases due either to HIV-1 in the exceptional long-term nonprogressors (LTNPs) or to HIV-2 in West Africa. To better understand characteristics of these two disease types we performed a multiplex comparative analysis of cell activation, exhaustion, and expression of coreceptors and restriction factors in CD4 T cells susceptible to harbor those viruses. We analyzed by flow cytometry the expression of HLA-DR, PD1, CCR5, CXCR6, SAMHD1, Blimp-1, and TRIM5α on CD4 T cell subsets from 10 HIV-1 LTNPs and 14 HIV-2 (12 nonprogressors and 2 progressors) of the ANRS CO-15 and CO-5 cohorts, respectively, and 12 HIV healthy donors (HD). The V3 loop of the HIV-1 envelope from 6 HIV-1+ LTNPs was sequenced to determine the CXCR6-binding capacity. Proportions of HLA-DR and PD1+ cells were higher in memory CD4 T subsets from HIV-1 LTNPs compared with HIV-2 and HD. Similar findings were observed for CCR5+ cells although limited to central-memory CD4 T cell (TCM) and follicular helper T cell subsets, whereas all major subsets from HIV-1 LTNPs contained less CXCR6+ cells compared with HIV-2. All six V3 loop sequences from HIV-1 LTNPs contained a proline at position 326. Proportions of SAMHD1+ cells were higher in all resting CD4 T subsets from HIV-1 LTNPs compared with the other groups, whereas Blimp-1+ and Trim5α+ cells did not differ. The CD4 T cell subsets from HIV-1 LTNPs differ from those of HIV-2-infected subjects by higher levels of activation, exhaustion, and SAMHD1 expression that can reflect the distinct patterns of host/virus relationships.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2020.0084DOI Listing
November 2020

Performance evaluation of two SARS-CoV-2 IgG/IgM rapid tests (Covid-Presto and NG-Test) and one IgG automated immunoassay (Abbott).

J Clin Virol 2020 11 3;132:104618. Epub 2020 Sep 3.

Université de Paris, INSERM UMR 1137 IAME, Laboratoire de Virologie, AP-HP, Hôpital Bichat-Claude Bernard, F-75018, Paris, France.

The aim of this study was to assess the analytical performances, sensitivity and specificity, of two rapid tests (Covid- Presto® test rapid Covid-19 IgG/IgM and NG-Test® IgM-IgG COVID-19) and one automated immunoassay (Abbott SARS-CoV-2 IgG) for detecting anti- SARS-CoV-2 antibodies. This study was performed with: (i) a positive panel constituted of 88 SARS-CoV-2 specimens collected from patients with a positive SARS-CoV-2 RT-PCR, and (ii) a negative panel of 120 serum samples, all collected before November 2019, including 64 samples with a cross-reactivity panel. Sensitivity of Covid-Presto® test for IgM and IgG was 78.4% and 92.0%, respectively. Sensitivity of NG-Test® for IgM and IgG was 96.6% and 94.9%, respectively. Sensitivity of Abbott IgG assay was 96.5% showing an excellent agreement with the two rapid tests (κ = 0.947 and κ = 0.936 for NGTest ® and Covid-Presto® test, respectively). An excellent agreement was also observed between the two rapid tests (κ = 0.937). Specificity for IgM was 100% and 86.5% for Covid-Presto® test and NG-Test®, respectively. Specificity for IgG was 92.0%, 94.9% and 96.5% for Covid-Presto®, NGTest ®, and Abbott, respectively. Most of the false positive results observed with NG-Test® resulted from samples containing malarial antibodies. In conclusion, performances of these 2 rapid tests are very good and comparable to those obtained with automated immunoassay, except for IgM specificity with the NG-Test®. Thus, isolated IgM should be cautiously interpreted due to the possible false-positive reactions with this test. Finally, before their large use, the rapid tests must be reliably evaluated with adequate and large panel including early seroconversion and possible cross-reactive samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2020.104618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470702PMC
November 2020

Conventional Dendritic Cells and Slan Monocytes During HIV-2 Infection.

Front Immunol 2020 13;11:1658. Epub 2020 Aug 13.

Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.

HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14CD16 monocytes were found to accumulate and CD11c conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16 inflammatory (intermediate, non-classical and slan monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection. We analyzed by flow cytometry these PBMC subsets from Paris area residents: 29 asymptomatic, untreated PLWHIV-2 from the IMMUNOVIR-2 study, part of the ANRS-CO5 HIV-2 cohort: 19 long-term non-progressors (LTNP; infection ≥8 years, undetectable viral load, stable CD4 counts≥500/μL; 17 of West-African origin -WA), and 10 non-LTNP (P; progressive infection; 9 WA); and 30 age-and sex-matched controls: 16 blood bank HD with unknown geographical origin, and 10 HD of WA origin (GeoHD). We measured plasma bacterial translocation markers by ELISA. Non-classical monocyte counts were higher in GeoHD than in HD (54 vs. 32 cells/μL, = 0.0002). Slan monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, = 0.0002). Thus cell counts were compared only between participants of WA origin. They were similar in LTNP, P and GeoHD, indicating that there were no HIV-2 related differences. cDC counts did not show major differences between the groups. Interestingly, inflammatory monocyte counts correlated with plasma sCD14 and LBP only in PLWHIV-2, especially LTNP, and not in GeoHD. In conclusion, in LTNP PLWHIV-2, inflammatory monocyte counts correlated with LBP or sCD14 plasma levels, indicating a potential innate immune response to subclinical bacterial translocation. As GeoHD had higher inflammatory monocyte counts than HD, our data also show that specific controls are important to refine innate immunity studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438582PMC
August 2020

HSV-2 Infection as a Potential Cofactor for HIV Disease Progression and Selection of Drug Resistance Mutations in Adults under WHO-Recommended First-Line Antiretroviral Therapy: A Multicentric, Cross-Sectional Study in Cameroon, Central African Republic, Chad, and Gabon.

Trop Med Infect Dis 2020 08 24;5(3). Epub 2020 Aug 24.

Laboratoire de Microbiologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, and Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.

Although herpes simplex virus-2 (HSV-2) infection is a known cofactor for HIV transmission in Central Africa, its role in HIV disease progression is unclear. The aim of this study was to examine the potential link between HSV-2 infection and HIV disease progression, in addition to identifying the presence of genes conferring HIV antiretroviral resistance mutations. This was a cross-sectional study involving 302 HIV-infected adults in Central Africa with virological failure (viral load >1000 copies/mL) on first-line antiretroviral therapy from four different countries. The seroprevalence of HSV-2 was 32% (96/302). Amongst the HIV-infected individuals who were HSV-2 seropositive, the mean HIV viral load and CD4 count were 4.82 ± 0.83 log copies/mL and 243 ± 144 cells/microliter, respectively. Among the HIV-infected individuals who were HSV-2-seronegative, the mean HIV viral load and CD4 count were 3.48 ± 0.44 log copies/mL and 646 ± 212 cells/microliter, respectively ( < 0.001). There was a statistically significant relationship ( < 0.001) between HSV-2 seropositivity and the presence of resistance mutations to antiretrovirals (ARV), non-nucleoside reverse transcriptase inhibitors (NNRTI), and nucleoside reverse transcriptase inhibitors (NRTI) with odds ratios of 9.7, 10, and 11.9, respectively. There was no link between HSV-2 serostatus and protease inhibitor (PI) resistance mutations. There was a substantial accumulation of resistance mutations in HSV-2-seropositive compared to -seronegative patients. These findings support the link between HIV disease progression and HSV-2 infection. An association was observed between the presence of NNRTI and NRTI resistance mutations and HSV-2 seropositivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/tropicalmed5030136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557575PMC
August 2020

No association between human herpesvirus or herpesvirus saimiri and idiopathic pulmonary fibrosis.

ERJ Open Res 2020 Jul 17;6(3). Epub 2020 Aug 17.

AP-HP, Hôpital Bichat-Claude Bernard, Service de Pneumologie, Centre de référence des maladies pulmonaires rares, Université de Paris, INSERM UMR1152, Paris, France.

https://bit.ly/2ZrKiDJ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00243-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430142PMC
July 2020

Survival among antiretroviral-experienced HIV-2 patients experiencing virologic failure with drug resistance mutations in Cote d'Ivoire West Africa.

PLoS One 2020 5;15(8):e0236642. Epub 2020 Aug 5.

Centre Inserm 1219 & Institut de Santé Publique d'épidémiologie et de développement, Université de Bordeaux, Bordeaux, France.

Introduction: The long-term prognosis of HIV-2-infected patients receiving antiretroviral therapy (ART) is still challenging, due to the intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) and the suboptimal response to some protease inhibitors (PI). The objective was to describe the 5-years outcomes among HIV-2 patients harboring drug-resistant viruses.

Methods: A clinic-based cohort of HIV-2-patients experiencing virologic failure, with at least one drug resistance mutation was followed from January 2012 to August 2017 in Côte d'Ivoire. Follow-up data included death, lost to follow-up (LTFU), immuno-virological responses. The Kaplan-Meier curve was used to estimate survival rates.

Results: A total of 31 HIV-2 patients with virologic failure and with at least one drug resistance mutation were included. Two-third of them were men, 28(90.3%) were on PI-based ART-regimen at enrolment and the median age was 50 years (IQR = 46-54). The median baseline CD4 count and viral load were 456 cells/mm3 and 3.7 log10 c/mL respectively, and the participants have been followed-up in median 57 months (IQR = 24-60). During this period, 21 (67.7%) patients switched at least one antiretroviral drug, including two (6.5%) and three (9.7%) who switched to a PI-based and an integrase inhibitor-based regimen respectively. A total of 10(32.3%) patients died and 4(12.9%) were LTFU. The 36 and 60-months survival rates were 68.5% and 64.9%, respectively. Among the 17 patients remaining in care, six(35.3%) had an undetectable viral load (<50 c/mL) and for the 11 others, the viral load ranged from 2.8 to 5.6 log10 c/mL. Twelve patients were receiving lopinavir at the time of first genotype, five(42%) had a genotypic susceptibility score (GSS) ≤1 and 4(33%) a GSS >2.

Conclusions: The 36-months survival rate among ART-experienced HIV-2 patients with drug-resistant viruses is below 70%,lower than in HIV-1. There is urgent need to improve access to second-line ART for patients living with HIV-2 in West Africa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236642PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406077PMC
October 2020

Purifying Selection in Human Immunodeficiency Virus-1 Gene in Perinatally Human Immunodeficiency Virus-1-Infected Children Harboring Discordant Immunological Response and Virological Nonresponse to Long-Term Antiretroviral Therapy.

J Clin Med Res 2020 Jun 4;12(6):369-376. Epub 2020 Jun 4.

Laboratoire de Virologie, Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris (AP-HP) and Universite de Paris, Paris Sorbonne Cite, Paris, France.

Background: Biological monitoring of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected pediatric population remains challenging. The aim of the present study was to assess the long-term HIV-1 genetic diversity in gene in HIV-1-infected children in virological failure under antiretroviral regimen adapted according to the successive World Health Organization (WHO) guidelines for resource-constrained settings.

Methods: HIV-1 diversity in gene was assessed in HIV-1-infected children and adolescents born from HIV-infected mothers (median age at follow-up: 13.8 years) in virological failure (VF) despite long-term regimen recommended by the WHO. The numbers of nonsynonymous substitutions per potential nonsynonymous site (dN) and of synonymous substitutions at potential synonymous sites (dS) in HIV-1 gene and the dN/dS ratios were used to estimate the selective pressure on circulating HIV-1.

Results: The immunological responses to ART basically corresponded to: 1) Full therapeutic failure with immunological (I) and virological nonresponses in one-quarter (24.6%) of study children ((I, VF) subgroup); 2) Discordant immunovirological responses with paradoxical high CD4 T cell counts (I) and high HIV-1 RNA load in the remaining cohort patients (75.4%) ((I, VF) subgroup). The mean dS was 1.8-fold higher in (I, VF) than (I, VF) subgroup (25.9 ± 18.4 vs. 14.3 ± 10.8). In the (I, VF) subgroup, the mean dS was 1.6-fold higher than the mean dN. Finally, the mean dN/dS ratio was 2.1-fold lower in (I, VF) than (I, VF) subgroup (0.6 ± 0.3 vs. 1.3 ± 0.7), indicating purifying selection in the immunovirological discordant (I, VF) subgroup and positive selection in the immunovirological failure (I, VF) subgroup.

Conclusions: Children and adolescents in immunovirological therapeutic failure harbor positive selection of HIV-1 strains favoring diversifying in -encoded amino acids. In contrast, children with persistent discordant immunovirological responses show accumulation of mutations and purifying selection in gene sequences, indicating limited genetic evolution and likely suggesting genetic adaptation of viruses to host functional constraints.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jocmr4157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295550PMC
June 2020

Escalating and sustained immunovirological dissociation among antiretroviral drug-experienced perinatally human immunodeficiency virus-1-infected children and adolescents living in the Central African Republic: A STROBE-compliant study.

Medicine (Baltimore) 2020 May;99(21):e19978

Laboratoire de virologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP) and Université Paris Descartes, Paris Sorbonne Cité, Paris, France.

Sub-Saharan Africa has the vast majority (∼90%) of new pediatric acquired immunodeficiency syndrome cases worldwide. Biologically monitoring HIV-infected pediatric populations remains challenging. The differential interest of human immunodeficiency virus (HIV)-1 RNA loads and CD4 T-cell counts is debated for the treatment of pediatric acquired immunodeficiency syndrome patients.Long-term antiretroviral treatment (ART) outcomes regarding immunological and virological surrogate markers were longitudinally evaluated between 2009 and 2014 (over 57 months) in 245 perinatally HIV-1-infected children and adolescents born from HIV-infected mothers, treated at inclusion for at least 6 months by the World Health Organization-recommended ART in Bangui, Central African Republic.Patients were monitored over time biologically for CD4 T-cell counts, HIV-1 RNA loads, and drug resistance mutation genotyping.Children lost to follow-up totaled 6%. Four categories of immunovirological responses to ART were observed. At baseline, therapeutic success with sustained immunological and virological responses was observed in 80 (32.6%) children; immunological and virologic nonresponses occurred in 32 (13.0%) children; finally, the majority (133; 54.2%) of the remaining children showed discordant immunovirological responses. Among them, 33 (13.4%) children showed rapid virological responses to ART with an undetectable viral load, whereas immunological responses remained absent after 6 months of treatment and increased progressively over time in most of the cases, suggesting slow immunorestoration. Notably, nearly half of the children (40.8% at baseline and 48.2% at follow-up) harbored discordant immunovirological responses with a paradoxically high CD4 T-cell count and HIV-1 RNA load, which are always associated with high levels of drug resistance mutations. The latter category showed a significant increase over time, with a growth rate of 1.23% per year of follow-up.Our STROBE-compliant study demonstrates the high heterogeneity of biological responses under ART in children with frequent passage from 1 category to another over time. Close biological evaluation with access to routine plasma HIV-1 RNA load monitoring is crucial for adapting the complex outcomes of ART in HIV-infected children born from infected mothers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000019978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249904PMC
May 2020

[Viral reservoir in HIV-2 infection: a model for attenuated retroviral infection].

Med Sci (Paris) 2020 Apr 1;36(4):336-339. Epub 2020 May 1.

Sorbonne Université, Inserm U1135, Centre d'immunologie et des maladies infectieuses, Cimi-Paris, AP-HP, Hôpital universitaire Pitié-Salpêtrière, F-75013 Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1051/medsci/2020046DOI Listing
April 2020

Human Immunodeficiency Virus-2 (HIV-2): A Summary of the Present Standard of Care and Treatment Options for Individuals Living with HIV-2 in Western Europe.

Clin Infect Dis 2021 Feb;72(3):503-509

Katholieke Universiteit, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Leuven, Belgium.

Human immunodeficiency virus-2 (HIV-2) is endemic in some countries in West Africa. Due to the lower prevalence in industrialized countries, there is limited experience and knowledge on the management of individuals living with HIV-2 in Europe. Compared to HIV-1, there are differential characteristics of HIV-2 regarding diagnostic procedures, the clinical course, and, most importantly, antiretroviral therapy. We integrated the published literature on HIV-2 (studies and reports on epidemiology, diagnostics, the clinical course, and treatment), as well as expert experience in diagnosing and clinical care, to provide recommendations for a present standard of medical care of those living with HIV-2 in Western European countries, including an overview of strategies for diagnosis, monitoring, and treatment, with suggestions for effective drug combinations for first- and second-line treatments, post-exposure prophylaxis, and the prevention of mother-to-child transmission, as well as listings of mutations related to HIV-2 drug resistance and C-C motif chemokine receptor type 5 and C-X-C motif chemokine receptor type 4 coreceptor tropism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa275DOI Listing
February 2021

Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients.

J Antimicrob Chemother 2020 06;75(6):1588-1590

Université de Paris, IAME, UMR1137, INSERM, Laboratoire de Virologie, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.

Background: GS-6207 is a first-in-class HIV capsid inhibitor, targeting several functions of the HIV capsid in the viral cycle, including viral particle assembly, capsid formation and nuclear entry. GS-6207 has demonstrated picomolar potency in vitro, activity confirmed by high potency in a Phase 1 clinical study, with a long-acting antiretroviral profile with potential dosing every 6 months. In vitro resistance selections previously conducted with increasing doses of GS-6207 have identified capsid variants with reduced susceptibility to GS-6207.

Objectives: To study the prevalence of capsid mutations associated with in vitro resistance to GS-6207 in people living with HIV (PLWH).

Methods: Plasma samples from ART-naive or -experienced PLWH, including PI-experienced people, were sequenced and analysed for the presence of capsid variants identified during in vitro resistance selection: L56I, M66I, Q67H, K70N, N74D, N74S and T107N.

Results: Among the samples from the 1500 patients studied, none of the seven GS-6207 resistance mutations identified during in vitro selection experiments was detected, regardless of HIV subtype or PLWH treatment history.

Conclusions: Out of the seven HIV capsid substitutions previously selected in vitro and shown to confer phenotypic resistance to GS-6207, none of these seven mutations was observed in this large dataset, suggesting that neither PLWH with previous PI failure nor PLWH with emergence of PI resistance mutations are anticipated to impact GS-6207 activity in these diverse HIV-infected populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa060DOI Listing
June 2020

Pharmacovirological analyses of blood and male genital compartment in patients receiving dolutegravir + lamivudine dual therapy as a switch strategy (ANRS 167 LAMIDOL trial).

J Antimicrob Chemother 2020 06;75(6):1611-1617

Université de Paris, INSERM UMR 1137 IAME, F-75018 Paris, France.

Objectives: To describe plasma residual HIV viraemia, cellular HIV reservoir size, blood plasma drug concentrations and their male genital tract penetration during the maintenance dual therapy dolutegravir + lamivudine.

Patients And Methods: ANRS167 LAMIDOL enrolled 104 virologically suppressed patients to switch to dolutegravir + lamivudine. In this pharmacovirological substudy, ultrasensitive plasma viral load (USpVL) and plasma drug concentrations were measured at Day 0 (D0), Week 24 (W24) and W48 of dolutegravir + lamivudine, and HIV-DNA was measured at W-8 and W48. Semen samples were collected at D0 and W24 from 18 participants. Total and unbound blood and seminal plasma drug concentrations were measured using UPLC-MS/MS.

Results: Median HIV-DNA was 2.5 log10 copies/106 PBMC (IQR = 2.2-3.0, n = 100) at W-8 and 2.4 log10 copies/106 PBMC (IQR = 2.1-2.9, n = 100) at W48 (P = 0.17). The proportion of patients with undetected USpVL was 38% (n = 98), 43% (n = 98) and 49% (n = 97) at D0, W24 and W48, respectively (P = 0.08). Total and unbound plasma dolutegravir concentrations were stable between timepoints (P = 0.13) and all total plasma dolutegravir concentrations except one were adequate. Median free fraction of dolutegravir in plasma was 0.21%. Median blood plasma and seminal plasma concentrations of total dolutegravir at 24 h were 1812 ng/mL and 206 ng/mL, respectively. Median seminal plasma/blood plasma total concentration ratios were 11.6% and 2478% for dolutegravir and lamivudine, respectively. HIV-RNA (365 to 475 copies/mL) was detected in seminal plasma of one patient at D0 (5.9%) and of two patients at W24 (11.8%).

Conclusions: These findings add further important information regarding the effectiveness of dolutegravir + lamivudine maintenance dual therapy in terms of plasma residual viraemia, cellular reservoir size and drug penetration in the male genital tract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa035DOI Listing
June 2020

M184V/I does not impact the efficacy of abacavir/lamivudine/dolutegravir use as switch therapy in virologically suppressed patients.

J Antimicrob Chemother 2020 05;75(5):1290-1293

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière - Charles Foix, laboratoire de virologie, F75013 Paris, France.

Background: M184V/I NRTI resistance mutations can be selected by either lamivudine/emtricitabine or abacavir. There are controversies about the use of abacavir/lamivudine/dolutegravir combinations in HIV-1-infected treatment-experienced patients with a fully suppressed HIV viral load (VL) and harbouring M184V/I.

Objectives: We assessed the efficacy of abacavir/lamivudine/dolutegravir when used in HIV-infected pretreated patients with an undetectable VL who previously harboured M184V/I as a unique NRTI resistance mutation in a genotypic resistance test and had no resistance to integrase inhibitors.

Patients And Methods: A total of 154 patients with a fully suppressed HIV-1 plasma VL (<50 copies/mL) treated with tenofovir disoproxil fumarate/emtricitabine/boosted PI or abacavir/lamivudine/boosted PI who switched to an abacavir/lamivudine/dolutegravir regimen and had M184V/I as a unique NRTI resistance mutation in their therapeutic history were retrospectively analysed up to 12 months after the switch to abacavir/lamivudine/dolutegravir. Assessment of residual viraemia was performed at Months 1, 3, 6 and 12. Plasma VL with undetectable HIV-1 RNA corresponded to an absence of residual viraemia.

Results: During the 12 months of follow-up, three patients had a blip of VL (53, 62 and 106 copies/mL) at Month 3 followed by a subsequent VL <50 copies/mL. No patient harboured a virological failure during the follow-up. Moreover, there was no change in residual viraemia during the follow-up.

Conclusions: M184V/I as a unique NRTI resistance mutation, regardless of possible selection by regimens containing lamivudine/emtricitabine or abacavir, does not affect the virological response of well-controlled patients who switched to abacavir/lamivudine/dolutegravir for at least 12 months.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa019DOI Listing
May 2020

Prevalence of doravirine-associated resistance mutations in HIV-1-infected antiretroviral-experienced patients from two large databases in France and Italy.

J Antimicrob Chemother 2020 04;75(4):1026-1030

Sorbonne Université, INSERM, UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de Virologie, Paris, France.

Objectives: Doravirine, a novel NNRTI, selects for specific mutations in vitro, including mutations at reverse transcriptase (RT) positions 106, 108, 188, 227, 230 and 234. The aim of this study was to examine the prevalence of doravirine-associated resistance mutations in HIV-1-infected antiretroviral-experienced patients.

Methods: Doravirine-associated resistance mutations identified in vitro or in vivo were studied in a set of 9199 HIV-1 RT sequences from HIV-1 antiretroviral-experienced patients, including 381 NNRTI-failing patients in France and Italy between 2012 and 2017. The following mutations were considered as resistance mutations: V106A/M, V108I, Y188L, G190S, F227C/L/V, M230I/L, L234I, P236L, K103N + Y181C, K103N + P225H and K103N + L100I.

Results: The frequencies of doravirine-associated resistance mutations (total dataset versus NNRTI-failing patients) were: V106A/M, 0.8% versus 2.6%; V108I, 3.3% versus 9.2%; Y188L, 1.2% versus 2.6%; G190S, 0.3% versus 2.1%; F227C/L/V, 0.5% versus 1.8%; M230I/L, 2.8% versus 0%; L234I, 0.1% versus 0.5%; K103N + Y181C, 3.9% versus 3.9%; K103N + P225H, 2.9% versus 4.7%; and K103N + L100I, 1.7% versus 3.9%, with a significantly higher proportion of these mutations in the NNRTI-failing group (P < 0.05), except for M230I/L and K103N + Y181C. The overall prevalence of sequences with at least one doravirine-associated resistance mutation was 12.2% and 34.9% in the total dataset and NNRTI-failing patients (P < 0.001), respectively. In comparison, the prevalence of the common NNRTI mutations V90I, K101E/P, K103N/S, E138A/G/K/Q/R/S, Y181C/I/V and G190A/E/S/Q were higher (8.9%, 7.9%, 28.6%, 12.6%, 14.2% and 8.9%, respectively).

Conclusions: These results suggest that doravirine resistance in antiretroviral-experienced patients generally and specifically among NNRTI-failing patients is lower than resistance to other NNRTIs currently used, confirming its distinguishing resistance pattern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz553DOI Listing
April 2020

Expanded Spectrum of Antiretroviral-Selected Mutations in Human Immunodeficiency Virus Type 2.

J Infect Dis 2020 06;221(12):1962-1972

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA.

Background: HIV-1 and HIV-2 differ in their antiretroviral (ARV) susceptibilities and drug resistance mutations (DRMs).

Methods: We analyzed published HIV-2 pol sequences to identify HIV-2 treatment-selected mutations (TSMs). Mutation prevalences were determined by HIV-2 group and ARV status. Nonpolymorphic mutations were those in <1% of ARV-naive persons. TSMs were those associated with ARV therapy after multiple comparisons adjustment.

Results: We analyzed protease (PR) sequences from 483 PR inhibitor (PI)-naive and 232 PI-treated persons; RT sequences from 333 nucleoside RT inhibitor (NRTI)-naive and 252 NRTI-treated persons; and integrase (IN) sequences from 236 IN inhibitor (INSTI)-naive and 60 INSTI-treated persons. In PR, 12 nonpolymorphic TSMs occurred in ≥11 persons: V33I, K45R, V47A, I50V, I54M, T56V, V62A, A73G, I82F, I84V, F85L, L90M. In RT, 9 nonpolymorphic TSMs occurred in ≥10 persons: K40R, A62V, K70R, Y115F, Q151M, M184VI, S215Y. In IN, 11 nonpolymorphic TSMs occurred in ≥4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, R231 5-amino acid insertions. Nine of 32 nonpolymorphic TSMs were previously unreported.

Conclusions: This meta-analysis confirmed the ARV association of previously reported HIV-2 DRMs and identified novel TSMs. Genotypic and phenotypic studies of HIV-2 TSMs will improve approaches to predicting HIV-2 ARV susceptibility and treating HIV-2-infected persons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289557PMC
June 2020

Genetic Variability of Long Terminal Repeat Region between HIV-2 Groups Impacts Transcriptional Activity.

J Virol 2020 03 17;94(7). Epub 2020 Mar 17.

Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.

The HIV-2 long terminal repeat (LTR) region contains several transcription factor (TF) binding sites. Efficient LTR transactivation by cellular TF and viral proteins is crucial for HIV-2 reactivation and viral production. Proviral LTRs from 66 antiretroviral-naive HIV-2-infected patients included in the French ANRS HIV-2 CO5 Cohort were sequenced. High genetic variability within the HIV-2 LTR was observed, notably in the U3 subregion, the subregion encompassing most known TF binding sites. Genetic variability was significantly higher in HIV-2 group B than in group A viruses. Notably, all group B viruses lacked the peri-ETS binding site, and 4 group B sequences (11%) also presented a complete deletion of the first Sp1 binding site. The lack of a peri-ETS binding site was responsible for lower transcriptional activity in activated T lymphocytes, while deletion of the first Sp1 binding site lowered basal or Tat-mediated transcriptional activities, depending on the cell line. Interestingly, the HIV-2 cellular reservoir was less frequently quantifiable in patients infected by group B viruses and, when quantifiable, the reservoirs were significantly smaller than in patients infected by group A viruses. Our findings suggest that mutations observed in HIV-2 LTR sequences are associated with differences in transcriptional activity and may explain the small cellular reservoirs in patients infected by HIV-2 group B, providing new insight into the reduced pathogenicity of HIV-2 infection. Over 1 million patients are infected with HIV-2, which is often described as an attenuated retroviral infection. Patients frequently have undetectable viremia and evolve at more slowly toward AIDS than HIV-1-infected patients. Several studies have reported a smaller viral reservoir in peripheral blood mononuclear cells in HIV-2-infected patients than in HIV-1-infected patients, while others have found similar sizes of reservoirs but a reduced amount of cell-associated RNA, suggesting a block in HIV-2 transcription. Recent studies have found associations between mutations within the HIV-1 LTR and reduced transcriptional activities. Until now, mutations within the HIV-2 LTR region have scarcely been studied. We conducted this research to discover if such mutations exist in the HIV-2 LTR and their potential association with the viral reservoir and transcriptional activity. Our study indicates that transcription of HIV-2 group B proviruses may be impaired, which might explain the small viral reservoir observed in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.01504-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081896PMC
March 2020

[Physiopathology of HIV-2 infection].

Virologie (Montrouge) 2019 10;23(5):277-291

Paris University, AP-HP, Hôpital Bichat-Claude-Bernard, IAME, Inserm, Laboratoire de virologie, 46 rue Henri-Huchard 75018 Paris, France.

The HIV-2 virus is not widely spread worldwide, with only one to three million infected people, mainly in West Africa. HIV-2 is responsible for an attenuated infection compared to HIV-1. Thus, HIV-2 infection is characterized by low and frequently undetectable viral loads and a slower course to AIDS. Describing the infection natural history differences between these two viruses, and then determining the mechanisms underlying the HIV-2 lower pathogenicity, is essential to identify the mechanisms underlying the immunopathogenicity of HIV infection. Studies conducted to date have identified both host-related and virus-related factors contributing to an improved immune control and the attenuated viral replication. In this review, we summarize the origins and epidemiology of HIV-2, the natural history of infection, the main virological tools for monitoring the infection course, and the main mechanisms explaining the attenuated infection of HIV-2. We also indicate the points remaining to be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/vir.2019.0789DOI Listing
October 2019

Was Zika introduced to Brazil by participants at the 2013 Beach Soccer World Cup held in Tahiti: A phylogeographical analysis.

Travel Med Infect Dis 2019 Nov 5:101512. Epub 2019 Nov 5.

Université de Paris, INSERM UMR 1137 IAME, F-75018, Paris, France; Laboratoire de Virologie, AP-HP, Hôpital Bichat-Claude Bernard, F-75018, Paris, France.

Background: Zika virus (ZIKV) was initially responsible for a limited number of punctual epidemics throughout Africa and Asia. Recently, large epidemics occurred in French Polynesia, Brazil and Pan-America. These outbreaks were associated with severe outcomes such as Guillain-Barré Syndrome and microcephaly of in-utero infected newborns. Previous studies demonstrated that ZIKV was introduced in Brazil from French Polynesia but failed to identify a founding event.

Method: All publicly available ZIKV full-genome sequences (n = 182) were phylogenetically analyzed, using Bayesian method, to estimate the introduction date of ZIKV into Brazil.

Results: Introduction date into Brazil was estimated between 8th of July 2013 and 4th of November 2013, encompassing the Beach Soccer World Cup held in French Polynesia, in September 2013, which gathered Brazilian athletes and supporters. We also observed that ZIKV sequences from travelers infected in South-East Asia or in Pacific islands were closely related to viruses identified prior to the French Polynesian epidemic, underlining an endemic circulation of ZIKV in those countries since 2007, at least.

Conclusion: This work provides a narrower estimation of ZIKV introduction into Brazil and illustrates the need for a better exploration of ZIKV circulation and endemicity in South-East Asia, while epidemiological and prevention efforts have been mainly focused on the Pan-American epidemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tmaid.2019.101512DOI Listing
November 2019

2019 update of the drug resistance mutations in HIV-1.

Top Antivir Med 2019 09;27(3):111-121

Veterans Affairs San Diego Healthcare System and University of California San Diego, La Jolla, CA, USA.

The 2019 edition of the IAS-USA drug resistance mutations list updates the Figure last published in January 2017. The mutations listed are those that have been identified by specific criteria for evidence and drugs described. The Figure is designed to assist practitioners in identifying key mutations associated with resistance to antiretroviral drugs, and therefore, in making clinical decisions regarding antiretroviral therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892618PMC
September 2019

Short Communication: Extremely Severe CD4 Lymphopenia During HIV-1 Primary Infection.

AIDS Res Hum Retroviruses 2019 10 12;35(10):930-933. Epub 2019 Sep 12.

Département d'Immunologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

We report the case of a patient with a very profound CD4 T cell lymphopenia <20 cells/mm in the context of a primary HIV-1 infection, associated with both delayed HIV-specific antibody and CD8 T cell responses. A long-term immune reconstitution was observed after immediate initiation of antiretroviral therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2019.0065DOI Listing
October 2019

HIV Infection in North African Patients.

AIDS Res Hum Retroviruses 2019 07 19;35(7):628-633. Epub 2019 Jun 19.

3 Infection Antimicrobials Modelling Evolution (IAME), UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

North Africa is one of the rare regions where the HIV epidemic is growing. In France, 5% of the migrants discovering their HIV infection are from North Africa. The objective of this study was to compare the sociodemographic characteristics and outcomes of North African and French HIV-infected patients. This study was conducted in the HIV clinic of Bichat Hospital (Paris, France). The North African HIV-infected patients were born in Algeria, Tunisia, or Morocco or had lived there for more than 6 months. They were matched for age and gender (1:2) to patients born in France who had never lived outside France for more than 6 months. Sociodemographic, clinical, and immunovirological characteristics of North African and French patients were compared using conditional logistic regression. Among 4,738 eligible patients, 285 North Africans were identified. CD4 levels at HIV diagnosis were not significantly different between North African and French patients, but were more frequently <200/mm in the former than the latter at treatment initiation ( = .02). CDC stage 3 disease occurred more frequently in the first 3 years of care in our center in North African patients than in French patients ( = .01), and control of the HIV viral load over the 12 months preceding inclusion was better in French patients ( = .0001). There was no difference regarding loss to care. These results highlight possible issues in adherence to antiretroviral treatment in North African patients, which may be related to differences in the acceptability of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/AID.2018.0292DOI Listing
July 2019

Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection.

PLoS Pathog 2019 05 16;15(5):e1007758. Epub 2019 May 16.

Sorbonne Université, Inserm 1135, Centre d'immunologie et des maladies infectieuses, Cimi-Paris, AP-HP, Hôpital universitaire Pitié-Salpêtrière, Paris, France.

The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1007758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541300PMC
May 2019

New mechanisms of resistance in virological failure to protease inhibitors: selection of non-described protease, Gag and Gp41 mutations.

J Antimicrob Chemother 2019 07;74(7):2019-2023

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France.

Objectives: To further characterize HIV-1 viruses of patients experiencing unexplained virological failure (VF) on PI-containing regimens, ultradeep sequencing was performed on protease, gag and gp41 genes in patients failing a first-line treatment.

Methods: All naive patients initiating an antiretroviral treatment based on boosted darunavir, atazanavir or lopinavir and experiencing VF without any transmitted drug resistance mutation detected by Sanger sequencing on protease and reverse transcriptase genes were selected. Ultradeep sequencing (IlluminaTM Nextera®) was performed on protease, gag and gp41 genes in plasma before initiation of treatment and at VF to identify emergent mutations.

Results: Among the 32 patients included in the study, emergent and previously undescribed mutations in the viral protease gene were identified in five patients at VF: 64M (1 CRF02_AG), 64M/70R with mutation 15V (2 CRF02_AG), 79A (1 CRF06_cpx) and 79A with mutation 15V (1 CRF02_AG). Two patients showed the emergence of R286K in the gag region, outside of cleavage sites (2 CRF02_AG). In the gp41 region, the V321I mutation emerged inside the cytoplasmic tail (1 subtype A and 1 subtype B). All these patients were treated with a darunavir/ritonavir-based regimen.

Conclusions: In some cases of VF to PIs, we observed the emergence of protease, Gag or Gp41 mutations that had not previously been associated with VF or PI resistance. These mutations should be further studied, in particular the 15V/64M/70R pattern in the protease gene identified among CRF02_AG viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz151DOI Listing
July 2019

New insights are game-changers in HIV-2 disease management.

Lancet HIV 2019 04;6(4):e214

INSERM, UMR 1137 IAME, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, AP-HP, Paris, France; Service de Maladies Infectieuses et Tropicales, Hôpital Bichat, AP-HP, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(19)30088-8DOI Listing
April 2019