scholarly journals Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients

2021 ◽  
Author(s):  
Romain Palich ◽  
Elisa Teyssou ◽  
Sophie Sayon ◽  
Basma Abdi ◽  
Cathia Soulie ◽  
...  
Keyword(s):  
Detection Threshold ◽  
Factors Associated ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
History Of ◽  
Viral Sequences ◽  
Kinetics Of ◽  
M184v Mutation

Abstract Background We aimed to assess the kinetics of drug-resistant viral variants (DRVs) harboring the M184V mutation in proviral DNA of long-term virally suppressed patients, and factors associated with DRV persistence. Methods Human immunodeficiency virus (HIV) DNA from blood cells stored in 2016 and 2019 was sequenced using Sanger and ultradeep sequencing (SS and UDS; detection threshold 1%) in antiretroviral therapy (ART)-treated patients with HIV RNA < 50 copies/mL for at least 5 years, with past M184V mutation documented in HIV RNA. Results Among 79 patients, by combining SS and UDS, M184V was found to be absent in 26/79 (33%) patients and persistent in 53/79 (67%). M184V-positive patients had a longer history of ART, lower CD4 nadir, and higher pretherapeutic HIV RNA. Among 37 patients with viral sequences assessed by UDS, the proportion of M184V-positive DRVs significantly decreased between 2016 and 2019 (40% vs 14%, P = .005). The persistence of M184V was associated with duration and level of HIV RNA replication under lamivudine/emtricitabine (3TC/FTC; P = .0009 and P = .009, respectively). Conclusions While it decreased over time in HIV DNA, M184V mutation was more frequently persistent in HIV DNA of more treatment-experienced patients with longer past replication under 3TC/FTC.

scholarly journals 945. Prevalence of HIV Associated Non-AIDS Conditions and Associated Risk Factors among Hospitalized HIV-infected Patients in India

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S504-S505
Author(s):  
Amyeo A Jereen ◽  
Celia Kucera ◽  
Saniya Pervin ◽  
Muralidhar Varma ◽  
Radhakrishnan Rajesh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Transmitted Disease ◽  
Multivariate Logistic Regression Analysis ◽  
Patient Risk ◽  
Sexually Transmitted ◽  
Factors Associated ◽  
Immunodeficiency Virus ◽  
History Of ◽  
Artery Disease ◽  
Associated Risk Factors

Abstract Background HIV-associated non-AIDS (HANA) conditions are becoming common as People Living with Human Immunodeficiency Virus (PLWHIV) age. However, data estimating the prevalence of HANA conditions and associated risk factors is lacking in developing countries. This study evaluates reasons for hospitalizations among PLWHIV in Udupi, India in the antiretroviral era, and describes associated risk factors. Methods Demographic and clinical data were extracted from medical charts of 1280 HIV-infected patients 18 years and older who were admitted to Kasturba Hospital, Manipal, India between January 1, 2013 and December 31, 2017, for a total of 2157 hospitalizations. Primary reasons for hospitalization were categorized into AIDS-defining vs Non-AIDS-defining and HANA vs Non-HANA conditions (Fig 1). Multivariate logistic regression analysis was performed to estimate demographic and clinical factors associated with hospitalizations due to AIDS-defining illness and HANA conditions. Categorization of Reasons for Hospitalization Results Patients’ median age was 45 (18-80) years; 70% male. Median age of patients with AIDS-defining illness (45% of hospitalizations) was lower at 44 (18-75) years compared with HANA (15% of hospitalizations) at 48 (21-80) years. Age (OR, 95% CI) (0.985, 0.974-0.995), admission CD4 (0.998, 0.997 - 0.998), history of hypertension (HTN) (0.59, 0.42-0.82), stroke (0.49, 0.24 - 0.93), diabetes (1.56, 1.10 - 2.19), and AIDS-defining cancers (1.74, 1.05 - 2.89) were associated with AIDS-defining hospitalizations (Fig 2). Additionally, age (1.016, 1.001 - 1.031), history of HTN (1.70, 1.16 - 2.46), coronary artery disease (CAD) (4.02, 1.87- 9.02), chronic kidney disease (CKD) (2.30, 1.15 - 4.61), stroke (2.93, 1.46 - 5.96), Hepatitis B (3.32, 1.66- 6.72), Hepatitis C (16.1, 2.84 - 314), sexually transmitted disease (STD) (3.76, 1.38- 10.8), and HANA-associated cancer (2.44, 1.28- 6.42) were associated with HANA hospitalizations (Fig 3). Patient Risk Factors for AIDS-related Hospitalization Patient Risk Factors for HANA-related Hospitalization Conclusion Prevalence of HANA conditions was lower than AIDS-defining illnesses possibly because of a younger population. Patients with AIDS-defining illnesses were also likely to have HANA conditions. Early detection and effective treatment of both HIV and HANA conditions is essential to decrease hospitalizations in low-resource settings. Disclosures All Authors: No reported disclosures

scholarly journals Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4+T Cell Activation during Antiretroviral Treatment

2014 ◽  
Vol 88 (14) ◽  
pp. 7818-7827 ◽  
Author(s):  
Sara Gianella ◽  
Marta Massanella ◽  
Douglas D. Richman ◽  
Susan J. Little ◽  
Celsa A. Spina ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Immune Activation ◽  
Genital Tract ◽  
Cell Activation ◽  
Future Studies ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Dna Reservoir

ABSTRACTAsymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4+T cells in blood (P< 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4+T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P= 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P= 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4+(P< 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations.IMPORTANCEAlmost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in blood, and the size of the HIV DNA reservoir in 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. In support of our primary hypothesis, shedding of CMV DNA in semen was associated with increased activation and proliferation of T cells in blood and also significantly higher levels of HIV DNA in blood cells. These results suggest that CMV reactivation might play a role in the maintenance of the HIV DNA reservoir during suppressive ART and that it could be a target of pharmacologic intervention in future studies.

scholarly journals 1265. Monitoring of Human Immunodeficiency Virus (HIV)-Infection Using the Cepheid HIV-1 Qualitative Assay

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S455-S455
Author(s):  
Erin Keizur ◽  
Drew Wood-Palmer ◽  
Maryann Koussa ◽  
Manuel Ocasio ◽  
Mary Jane Rotheram-Borus ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Los Angeles ◽  
Hiv Infection ◽  
Whole Blood ◽  
Viral Rna ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Pcr Test

Abstract Background Human immunodeficiency virus (HIV)-1 RNA quantification is the primary method of monitoring response to antiretroviral therapy. In the U.S. viral RNA testing is recommended for all HIV-infected patients at entry into care, at initiation or modification of therapy, and on a regular basis thereafter. HIV-1 DNA testing may pose additional advantages. For example, proviral DNA may predict early loss of viral suppression. The Cepheid® (Sunnyvale, CA) HIV-1 Qualitative (HIV Qual) assay detects total nucleic acid for both RNA and DNA and provides a qualitative result (HIV detectable or undetectable). Methods We tested participants aged 14–24 years old from the Adolescent Trials Network (ATN) CARES study with known HIV infection in Los Angeles, California and New Orleans, Louisiana. We tested participants using the Cepheid® HIV Qual assay and the quantitative HIV-1 RNA, real-time PCR test using the COBAS P6800 system (Roche, Branchburg, NJ). We used 100 μL of whole blood for the HIV Qual assay and results were provided in 90 minutes. We sent the remainder of the whole blood from the same visit to a commercial laboratory for HIV-RNA PCR testing and results were reported as “detected,” “detected, <20 copies/mL plasma” or “not detected, <20 copies/mL plasma.” We compared HIV Qual and HIV RNA PCR test results from the same visit for each participant. Results Overall, 57 HIV Qual tests were performed with concurrent HIV RNA PCR tests. Of those, 9/15 tests were concordant with HIV viral RNA suppression while 39/42 tests were concordant with HIV viral RNA detection. In 6 cases, the HIV RNA was not detected at <20 copies/mL by the Roche PCR while the HIV Qual assay detected HIV DNA. Of those 6 cases, 3 had subsequent HIV RNA PCR testing. All 3 cases had detectable HIV RNA at their next testing date (214 copies/mL, detected <20 copies/mL, 2130 copies/mL). Conclusion The HIV Qual test is feasible for the monitoring of HIV-infection. Due to its detection of HIV DNA, it may predict future lack of HIV RNA suppression. Disclosures All authors: No reported disclosures.

scholarly journals Natural History of Intestinal Microsporidiosis among Patients Infected with Human Immunodeficiency Virus

1999 ◽  
Vol 37 (10) ◽  
pp. 3421-3422 ◽  
Author(s):  
Kristin Dascomb ◽  
Rebecca Clark ◽  
Judith Aberg ◽  
Joseph Pulvirenti ◽  
Ross G. Hewitt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Natural History ◽  
Chart Review ◽  
Protease Inhibitor Therapy ◽  
Persistent Diarrhea ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
History Of ◽  
Weight Loss Predictors ◽  
Intestinal Microsporidiosis

A chart review of 73 human immunodeficiency virus (HIV)-infected patients with enteric microsporidiosis was conducted to define the natural history of microsporidiosis. A substantial proportion of patients remained symptomatic after 6 months (54.8% with persistent diarrhea and 51.2% with weight loss). Predictors for persistent diarrhea included high HIV RNA viral load and no initiation of protease inhibitor therapy.

scholarly journals T stage and venous invasion are crucial prognostic factors for long-term survival of patients with remnant gastric cancer: a cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kentaro Matsuo ◽  
Sang-Woong Lee ◽  
Ryo Tanaka ◽  
Yoshiro Imai ◽  
Kotaro Honda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Venous Invasion ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Long Term Survival ◽  
Factors Associated ◽  
T Stage ◽  
History Of

Abstract Background The incidence of remnant gastric cancer (RGC) after distal gastrectomy is 1–5%. However, as the survival rate of patients with gastric cancer improves due to early detection and treatment, more patients may develop RGC. There is no consensus on the surgical and postoperative management of RGC, and the clinicopathological characteristics correlated with the long-term outcomes remain unclear. Therefore, we investigated the clinicopathological factors associated with the long-term outcomes of RGC. Methods We included 65 consecutive patients who underwent gastrectomy for RGC from January 2000 to December 2015 at the Osaka Medical and Pharmaceutical University Hospital, Japan. The Kaplan–Meier method was used to create survival curves, and differences in survival were compared between the groups (clinical factors, pathological factors, and surgical factors) using the log-rank test. Multivariate analyses using the Cox proportional hazard model were used to identify factors associated with long-term survival. Results No significant differences were noted in the survival rate based on clinical factors (age, body mass index, diabetes mellitus, hypertension, cardiovascular disease, pulmonary complications, liver disease, diet, history of alcohol drinking, and history of smoking) or the type of remnant gastrectomy. Significant differences were noted in the survival rate based on pathological factors and surgical characteristics (intraoperative blood loss, operation time, and the number of positive lymph nodes). Multivariate analysis revealed that the T stage (hazard ratio, 5.593; 95% confidence interval [CI], 1.183–26.452; p = 0.030) and venous invasion (hazard ratio, 3.351; 95% CI, 1.030–10.903; p = 0.045) were significant independent risk factors for long-term survival in patients who underwent radical resection for RGC. Conclusions T stage and venous invasion are important prognostic factors of long-term survival after remnant gastrectomy for RGC and may be keys to managing and identifying therapeutic strategies for improving prognosis in RGC.

scholarly journals Risk Factors for Long-Term Vancomycin-Resistant Enterococci Persistence—A Prospective Longitudinal Study

2019 ◽  
Vol 7 (10) ◽  
pp. 400 ◽  
Author(s):  
Correa-Martinez ◽  
Stollenwerk ◽  
Kossow ◽  
Schaumburg ◽  
Mellmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Infection Control ◽  
Control Measures ◽  
Factors Associated ◽  
Infection Control Measures ◽  
Vancomycin Resistant Enterococci ◽  
History Of ◽  
Vancomycin Resistant ◽  
Prospective Longitudinal

Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that require effective infection control measures, representing a challenge for healthcare systems. This study aimed at identifying risk factors associated with prolonged VRE carriage and determining the rate of clearance that allows the discontinuation of contact precautions. During a 2-year study, screening was performed in patients with a history of VRE or at risk of becoming colonized. After bacterial identification and antibiotic susceptibility testing, glycopeptide resistance was confirmed by PCR. Isolates were compared via whole genome sequence-based typing. Risk factors were recorded, and follow-up screening was performed upon readmission, defining patients as long-term carriers if still colonized ≥10 weeks after first detection. Of 1059 patients positive for VRE, carriage status was assessed upon readmission in 463 patients. VRE was cleared in 56.4% of the cases. Risk factors associated with long-term persistence were hospital stays (frequency, length), hemato-oncological disease, systemic treatment with steroids, and use of antibiotics. No specific genotypic clustering was observed in patients with VRE clearance or persistence. VRE clearance is possibly underestimated. The identification of risk factors favoring long-term carriage may contribute to a targeted implementation of infection control measures upon readmission of patients with history of VRE.

scholarly journals Thyrotoxic Atrial Fibrillation: Factors Associated with Persistence and Risk of Ischemic Stroke

2017 ◽  
Vol 2017 ◽  
pp. 1-11
Author(s):  
Cheuk-Lik Wong ◽  
Ho-Kee Vicki Tam ◽  
Chun-Kit Vincent Fok ◽  
Pong-Kai Ellen Lam ◽  
Lai-Ming Fung
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Significant Proportion ◽  
Persistent Atrial Fibrillation ◽  
High Rate ◽  
Factors Associated ◽  
History Of ◽  
Reduce Risk ◽  
Free Thyroxine Level

Background. Atrial fibrillation (AF) is one of the commonest cardiovascular manifestations of thyrotoxicosis. A significant proportion of patients have persistent AF which may have long term consequences, for example, ischemic stroke. Methods. We performed a retrospective cohort study in a regional hospital from January 2004 to June 2016 to examine the clinical characteristics and outcomes of thyrotoxic patients who presented with atrial fibrillation and to investigate possible factors associated with persistent atrial fibrillation and ischemic stoke. Results. Among 1918 patients who had a diagnosis of thyrotoxicosis, 133 (6.9%) patients presented with AF. Spontaneous sinus conversion occurred in 89 (66.9%) patients in which 85 (94%) patients developed sinus conversion before or within 6 months after having achieved euthyroidism. The remaining 44 (33.1%) had persistent AF. The rate of ischemic stroke was numerically higher among patients who had persistent AF than those with spontaneous sinus conversion (15.9% versus 10.1%; log-rank 0.442, p=0.506). Patients who sustained an ischemic stroke were older (71 ± 11 years versus 62 ± 16 years, p=0.023) and had a trend towards higher CHA2DS2-VASc score (2.9 ± 1.7 versus 2.3 ± 1.7, p=0.153). History of smoking (adjusted odds ratio 4.9, 95% CI [1.8,14.0], p=0.002), a larger left atrial diameter (adjusted odd ratio 2.6, 95% CI [1.2,5.5], p=0.014), and a relatively lower free thyroxine level at diagnosis (adjusted odd ratio 2.1, 95% CI [1.2,3.5], p=0.008) were associated with persistence of AF on multivariate analysis. Conclusion. Persistence of thyrotoxic AF occurred in one-third of patients and spontaneous sinus conversion was unlikely after six months of euthyroidism. High rate of ischemic stroke was observed among patients with persistent thyrotoxic AF and older age. Patients with factors associated with persistent AF, especially older people, should be closely monitored beyond 6 months so that anticoagulation can be initiated in a timely manner to reduce risk of ischemic stroke.

scholarly journals Intact Human Immunodeficiency Virus (HIV) Reservoir Estimated by the Intact Proviral DNA Assay Correlates With Levels of Total and Integrated DNA in the Blood During Suppressive Antiretroviral Therapy

2020 ◽  
Author(s):  
Emmanouil Papasavvas ◽  
Livio Azzoni ◽  
Brian N Ross ◽  
Matthew Fair ◽  
Zhe Yuan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Hiv Reservoir ◽  
Dna Assay ◽  
Proviral Dna ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Immunodeficiency Virus

Abstract Accurate characterization of the human immunodeficiency virus (HIV) reservoir is imperative to develop an effective cure. HIV was measured in antiretroviral therapy-suppressed individuals using the intact proviral DNA assay (IPDA), along with assays for total or integrated HIV DNA, and inducible HIV RNA or p24. Intact provirus correlated with total and integrated HIV.

scholarly journals Human Immunodeficiency Virus (HIV)-Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children

2018 ◽  
Vol 8 (5) ◽  
pp. 433-438 ◽  
Author(s):  
Salvatore Rocca ◽  
Paola Zangari ◽  
Nicola Cotugno ◽  
Anita De Rossi ◽  
Bridget Ferns ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Antibody Responses ◽  
Hiv Dna ◽  
Art Initiation ◽  
Therapy Initiation ◽  
Immunodeficiency Virus ◽  
Dna Size ◽  
Hiv 1 ◽  
Plasma Assay

Different specific antibody responses against 10 HIV-1 viral proteins detected by Western blot, plasma assay on a very small amount of plasma (20 μL) can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children.

scholarly journals Factors Associated with the Selection of Mutations Conferring Resistance to Protease Inhibitors (PIs) in PI-Experienced Patients Displaying Treatment Failure on Darunavir

2007 ◽  
Vol 52 (2) ◽  
pp. 491-496 ◽  
Author(s):  
Sidonie Lambert-Niclot ◽  
Philippe Flandre ◽  
Ana Canestri ◽  
Gilles Peytavin ◽  
Christine Blanc ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Resistance Mutation ◽  
Transcriptase Inhibitor ◽  
Resistance Mutations ◽  
Factors Associated ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Selection Of

ABSTRACT The objective of this study was to characterize the mutations selected by darunavir (DRV) use in protease inhibitor (PI)-experienced patients and the associated factors. We analyzed treatment failure in 54 PI-experienced human immunodeficiency virus (HIV)-infected patients on a DRV- and ritonavir-containing regimen. Viral genotyping was carried out at the baseline, at between 1 and 3 months of treatment, and at between 3 and 6 months of treatment to search for the selection of mutations conferring resistance to PIs. The median baseline HIV RNA level was 4.9 log10 copies/ml, and the median CD4 count was 87 cells/mm3. At the baseline, the median numbers of resistance mutations were as follows: 3 DRV resistance mutations, 4 major PI resistance mutations, and 10 minor PI resistance mutations. The most common mutations that emerged at rebound included V32I (44%), I54M/L (24%), L33F (25%), I84V (21%), and L89V (12%). Multivariate analysis showed that higher baseline HIV RNA levels and smaller numbers of nucleoside reverse transcriptase inhibitor simultaneously used with DRV were associated with a higher risk of DRV resistance mutation selection. By contrast, L76V, a known DRV resistance mutation, was found to decrease the risk of selection of another DRV resistance mutation. The occurrence of virological failure while a patient was on DRV was associated with the selection of mutations that increased the level of DRV resistance without affecting susceptibility to tipranavir (TPV). In these PI-treated patients who displayed treatment failure while they were on a DRV-containing regimen, we confirmed the set of emerging mutations associated with DRV failure and identified the factors associated with the selection of these mutations. TPV susceptibility does not seem to be affected by the selection of a DRV resistance mutation.

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