Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study

2019 ◽  
Vol 75 (1) ◽  
pp. 194-199
Author(s):  
Sara Modica ◽  
David Redi ◽  
Roberta Gagliardini ◽  
Emanuela Giombini ◽  
Antonia Bezenchek ◽  
...  
Keyword(s):  
Resistance Mutations ◽  
Antiretroviral Drug Resistance ◽  
Antiretroviral Drug ◽  
History Of ◽  
Tenofovir Alafenamide ◽  
The Impact ◽  
Hiv 1 ◽  
Drug Resistant Virus

Abstract Background Antiretroviral drug resistance mutations remain a major cause of treatment failure. Objectives To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens. Materials and methods We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL. Results We included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39–53), 7 years (3–16) of HIV infection, nadir CD4+ 247 cells/mm3 (105–361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3–12.5) versus 3.8% (2.1–5.5) in virologically suppressed patients and 66.7% (39.5–93.9) versus 11.2% (6.5–15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02–1.27, P=0.024) in viraemic patients. Conclusions A switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.

scholarly journals ACQUIRED ANTIRETROVIRAL DRUG RESISTANCE MUTATIONS UPON TREATMENT FAILURE IN HIV-1 INFECTED PEDIATRIC PATIENTS IN CENTRAL BRAZIL

2020 ◽  
Vol 49 (2) ◽  
pp. 79-93
Author(s):  
Maly Albuquerque ◽  
Solomar Martins Marques ◽  
Ricardo Vieira Teles Filho ◽  
Paulo Sergio Sucasas Costa
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Children And Adolescents ◽  
Resistance Mutations ◽  
Central Brazil ◽  
Antiretroviral Drug Resistance ◽  
Drug Resistance Mutations ◽  
Antiretroviral Drug ◽  
Hiv 1

Antiretroviral drug-resistance mutations compromise the successful treatment of children and adolescents infected with human immunodeficiency virus type 1 (HIV-1). We describe the clinical, virological, and immunological follow-up of a cohort of children and adolescents perinatally infected with HIV-1 treated at Hospital Estadual de Doenças Tropicais Dr. Anuar Auad – HDT, in Central Brazil, after therapeutic failure related to drug resistance mutations.We analyzed the results of the genotypic test (protease codons 1–99 and reverse transcriptase codons 1–325) performed from 2003 to 2015. The ARV susceptibility profile was analyzed according to Stanford HIV drug resistance database. A total of 65 patients (median age of 10 years; range, 18 m–18 y) with therapeutic failure (after a median of 55 months of follow up; range, 9 m–13 y) and plasma levels of HIV-1 RNA greater than 1,000 copies/mL which were included and demonstrated mutations in: nucleoside reverse transcriptase inhibitors (NRTIs), 98.5%; non nucleoside reverse transcriptase inhibitors (NNRTIs), 75.4%; and protease inhibitors (PI), 44.6%. The most frequent NRTI mutations were found in codon T215 (83.1%) with a predominance of T215Y (56.9%), followed by M184V (69.3%). In the NNRTI class, mutations K103N (36.9%) and 190A (23.1%) were predominant, and, in the protease, mutations 54VL (35.4%) and 82ASTL (32.3%) were found in approximately the same proportion, with a predominance of the M54V mutation. These results demonstrate the high levels of resistance to different classes of antiretrovirals in HIV-infected children and adolescents and the importance of genotypic resistance tests in this population.KEY WORDS: HIV; drug resistance; genotypes; child; adolescent.

Long-term prognosis of patients withJ-wave syndrome

Heart ◽  
2019 ◽  
Vol 106 (4) ◽  
pp. 299-306
Author(s):  
Tsukasa Kamakura ◽  
Tetsuji Shinohara ◽  
Kenji Yodogawa ◽  
Nobuyuki Murakoshi ◽  
Hiroshi Morita ◽  
...  
Keyword(s):  
High Amplitude ◽  
Long Term Study ◽  
St Segment ◽  
History Of ◽  
Provocation Testing ◽  
Long Term Prognosis ◽  
Electrocardiographic Parameters ◽  
The Impact

ObjectiveLimited data are currently available regarding the long-term prognosis of patients with J-wave syndrome (JWS). The aim of this study was to investigate the long-term prognosis of patients with JWS and identify predictors of the recurrence of ventricular fibrillation (VF).MethodsThis was a multicentre retrospective study (seven Japanese hospitals) involving 134 patients with JWS (Brugada syndrome (BrS): 85; early repolarisation syndrome (ERS): 49) treated with an implantable cardioverter defibrillator. All patients had a history of VF. All patients with ERS underwent drug provocation testing with standard and high intercostal ECG recordings to rule out BrS. The impact of global J waves (type 1 ECG or anterior J waves and inferolateral J waves in two or more leads) on the prognosis was evaluated.ResultsDuring the 91±66 months of the follow-up period, 52 (39%) patients (BrS: 37; ERS: 15) experienced recurrence of VF. Patients with BrS and ERS with global J waves showed a significantly higher incidence of VF recurrence than those without (BrS: log-rank, p=0.014; ERS: log-rank, p=0.0009). The presence of global J waves was a predictor of VF recurrence in patients with JWS (HR: 2.16, 95% CI 1.21 to 3.91, p=0.0095), while previously reported high-risk electrocardiographic parameters (high-amplitude J waves ≥0.2 mV and J waves associated with a horizontal or descending ST segment) were not predictive of VF recurrence.ConclusionsThis multicentre long-term study showed that the presence of global J waves was associated with a higher incidence of VF recurrence in patients with JWS.

scholarly journals Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Flaminia Olearo ◽  
Huyen Nguyen ◽  
Fabrice Bonnet ◽  
Sabine Yerly ◽  
Gilles Wandeler ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Antiviral Treatment ◽  
Composite Endpoint ◽  
Hiv Treatment ◽  
Hiv Positive ◽  
Prior History ◽  
History Of ◽  
The Impact ◽  
Hiv 1

Abstract Objective The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. Method This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. Results We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154–441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2–79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4–21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35–4.59 and HR 1.66; 95% CI, 0.81–3.43, respectively). Conclusions In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.

scholarly journals HIV-1 pol gene diversity and antiretroviral drug resistance mutations in Itanhaém city, Brazil

2008 ◽  
Vol 11 (Suppl 1) ◽  
pp. P196
Author(s):  
RB Rodrigues-Matias ◽  
KCP Guatelli ◽  
RF Ambar ◽  
NB Duarte ◽  
LH Gagliani ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Gene Diversity ◽  
Resistance Mutations ◽  
Antiretroviral Drug Resistance ◽  
Drug Resistance Mutations ◽  
Antiretroviral Drug ◽  
Hiv 1

scholarly journals Long-term follow-up: tuberculosis, bronchiectasis and chronic pulmonary aspergillosis

Pneumologia ◽  
2019 ◽  
Vol 68 (3) ◽  
pp. 138-143
Author(s):  
Oxana Munteanu ◽  
Dumitru Chesov ◽  
Doina Rusu ◽  
Irina Volosciuc ◽  
Victor Botnaru
Keyword(s):  
Past History ◽  
Natural Evolution ◽  
Pulmonary Aspergillosis ◽  
Long Term Follow Up ◽  
History Of ◽  
Chronic Pulmonary Aspergillosis ◽  
The Impact

Abstract Pulmonary sequelae related to tuberculosis (TB) are among the major causes of bronchiectasis in Eastern Europe. The role of bacterial colonisation in the pathogenesis of bronchiectasis has been continuously studied over the last decades, less understood remains the impact of fungal infection, alone or in association with bacterial. Although the data on the development of chronic pulmonary aspergillosis (CPA) secondary to TB are scarce, recent evidence suggests a higher prevalence of CPA in patients with a past history of pulmonary TB than it was previously estimated. We present a case of natural evolution of CPA, with a radiological follow-up, in a patient with post-tuberculous bronchiectasis.

Prevalence of HIV-1 Subtypes and Antiretroviral Drug Resistance Mutations in Nepal

2016 ◽  
Vol 14 (6) ◽  
pp. 517-524 ◽  
Author(s):  
Nirajan Bhusal ◽  
Ruengpung Sutthent ◽  
Navin Horthongkham ◽  
Niracha Athipanyasilp ◽  
Wannee Kantakamalakul
Keyword(s):  
Drug Resistance ◽  
Resistance Mutations ◽  
Antiretroviral Drug Resistance ◽  
Drug Resistance Mutations ◽  
Antiretroviral Drug ◽  
Hiv 1
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