Antiviral Therapy[JOURNAL]
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200 papers
CD4:CD8 T-cell ratio changes in people with HIV receiving antiretroviral treatment.
Vivancos-Gallego MJ, Okhai H, Perez-Elías MJ … +12 more , Gomez-Ayerbe C, Moreno-Zamora A, Casado JL, Quereda C, Sanz JM, Sanchez-Conde M, Serrano-Villar S, Del Campo S, Dronda F, Galan JC, Sabin CA, Moreno S
Antivir Ther · 2020 · PMID 32338638 · Publisher ↗
BACKGROUND: Cofactors associated with persistently abnormal CD4:CD8 T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART d...
BACKGROUND: Cofactors associated with persistently abnormal CD4:CD8 T-cell ratio in people with HIV (PWH) on antiretroviral treatment (ART) might change over time as the population of people with HIV ages or as new ART drugs become available. The main objective of our study was to determine the long-term associations of baseline factors, including the CD4 T-cell count and ratio, with ratio normalization (≥1). In addition to this, we explored whether the ratio remained associated with the risk of both AIDS and non-AIDS events among individuals on suppressive ART. METHODS: Clinic-based study in a tertiary, university hospital in Madrid. People with HIV starting a first-line ART regimen (January 2006-June 2017) were included in a prospective national multicentre cohort (CoRIS). People with controlled HIV-infection within the first year of ART initiation and complete CD4 and CD8 T-cell records were selected. Cox proportional hazard (PH) regression models were used to estimate the cumulative incidence of ratio normalization and to examine associations with socio-demographic and clinical variables. To investigate factors independently associated with the development of AIDS and non-AIDS events we used a time updated Poisson regression model. RESULTS: The study included 557 subjects. During follow-up (median 5.24 years), 44% of participants achieved a ratio of 1 within a median of 1.49 years. In a multivariate PH model, pre-ART factors negatively associated with ratio normalization were the pre-ART CD4:CD8 T-cell ratio and mode of HIV acquisition. For the secondary analysis, 1.3 events/100 person years of follow-up were observed. After adjustment, older age, HIV RNA >200 copies/ml and CD4:CD8 T-cell ratios over follow-up, remained significantly associated with the development of AIDS and non-AIDS events. In contrast, pre-ART ratio was not associated with the risk of AIDS and non-AIDS events. CONCLUSIONS: In summary, our study showed that higher pre-ART CD4:CD8 T-cell ratio is associated with rates of ratio normalization ≥1. In addition, the risk of AIDS and non-AIDS events seems to be predicted by the time updated CD4:CD8 T-cell ratio not by the pre-ART CD4:CD8 T-cell ratio. Therefore, CD4:CD8 T-cell ratio should be considered as a dynamic marker for translation into clinical practice.
DAA-based treatment for HIV-HCV-coinfected patients: analysis of factors of sustained virological response in a real-life study.
Alessio L, Onorato L, Sangiovanni V … +15 more , Borrelli F, Manzillo E, Esposito V, Simeone F, Martini S, Capoluongo N, Leone S, Di Filippo G, D'Abbraccio M, Aprea L, Megna AS, Milano E, Rizzo V, Saracino A, Coppola N
Antivir Ther · 2020 · PMID 32314978 · Publisher ↗
BACKGROUND: The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and th...
BACKGROUND: The aim of the present study was to evaluate in HIV-infected patients treated with a direct-acting antiviral agent (DAA)-based regimen the variables associated with sustained virological response (SVR) and the trend in biochemical parameters and clinical events during and after DAA regimen. METHODS: We performed a multicentre retrospective cohort study, enrolling all 243 HIV-HCV-coinfected adult patients treated with DAAs between January 2015 and December 2018 in one of the nine participating Infectious Disease Centers in southern Italy, eight in Campania and one in Apulia. RESULTS: Of the 243 patients enrolled, 233 (95.9%) obtained an SVR at 12 weeks (SVR12). Of the 10 patients with non-SVR, 7 were tested for NS3, NS5A and NS5B resistance-associated substitutions (RASs) by sequencing analysis and 6 showed at least 1 major RAS in 1 HCV region (all in NS5A, 2 in NS5B and 1 in NS3). Comparing the 233 patients achieving SVR and the 10 non-achievers, no variable was independently associated with non-SVR. During and after DAA regimen, no modification in the biochemical parameters and clinical events was observed; however, the serum cholesterol and low-density lipoprotein (LDL) levels showed an increase (from 159 ±41.3 mg/dl at baseline to 174 ±44.5 mg/dl at week 12 after stopping treatment, P<0.001, and from 92 ±34.6 mg/dl to 109.4 ±73.7 mg/dl, P=0.002, respectively). CONCLUSIONS: The treatment with DAAs led to a high SVR12 rate in HIV-HCV-coinfected subjects, irrespective of epidemiological, clinical or virological characteristics. However, the DAA regimen was associated with an increase in total- and LDL-cholesterol, to be taken into account in the management of HIV infection.
Multidrug-resistant cytomegalovirus infection in a patient with granulomatosis with polyangiitis during immunosuppressive treatment.
Piccirilli G, Chiereghin A, Maritati M … +6 more , Turello G, Felici S, La Corte R, Gabrielli L, Contini C, Lazzarotto T
Antivir Ther · 2020 · PMID 32297594 · Publisher ↗
Cytomegalovirus (CMV) infection is a major complication in immunocompromised patients, including those with autoimmune diseases. Here, we describe the first case of granulomatosis with polyangiitis treated with steroids...
Cytomegalovirus (CMV) infection is a major complication in immunocompromised patients, including those with autoimmune diseases. Here, we describe the first case of granulomatosis with polyangiitis treated with steroids and cyclophosphamide, complicated by a multidrug-resistant (MDR) CMV infection in presence of weak antiviral cellular immunity. Since reports regarding CMV infection in rheumatological patients are rarely described and no guidelines on its management exist, the described case contributes to identify potential strategies to predict the risk of CMV disease and developing of MDR-CMV in these patients, through virological and immunological surveillance.
Real-life use of elbasvir/grazoprevir in adults and elderly patients: a prospective evaluation of comedications used in the PITER cohort.
Quaranta MG, Rosato S, Ferrigno L … +17 more , Amoruso DC, Monti M, Di Stefano P, Filomia R, Biliotti E, Migliorino G, Russo FP, Degasperi E, Chemello L, Brancaccio G, Blanc P, Cannizzaro M, Barbaro F, Morsica G, Licata A, Kondili LA, PITER collaborating group
Antivir Ther · 2020 · PMID 32242526 · Publisher ↗
BACKGROUND: In patients treated for HCV infection, potential drug-drug interactions (DDIs) can occur among direct-acting antiviral drugs (DAAs) and comedications used. The real-life effectiveness and safety of elbasvir/g...
BACKGROUND: In patients treated for HCV infection, potential drug-drug interactions (DDIs) can occur among direct-acting antiviral drugs (DAAs) and comedications used. The real-life effectiveness and safety of elbasvir/grazoprevir (ELB/GZR) among co-medicated HCV patients was evaluated. METHODS: We prospectively evaluated consecutive patients from 15 clinical centres participating in PITER who were treated with ELB/GZR and had been followed for at least 12 weeks after treatment. Data were prospectively collected on the use of comedications (including discontinuation, dose modification and addition of drugs) and potential DDIs with DAAs. RESULTS: Of the 356 patients with at least 12-week post-treatment follow-up (median age 67, range 50-88 years), 338 (95%) achieved sustained virological response. Of these, 219 (60%) had at least one comorbidity (median 2, range 1-6); information on comedication was available for 212 of them. Of 190 comedications used, 15 (8%) drugs were modified during ELB/GZR therapy, specifically in 9 (4%) patients they were interrupted, in 2 (1%) of whom, the comedication was interrupted before the DAA therapy because of potential DDI (that is, patients treated with carbamazepine); in 12 (6%) patients the comedications were modified in terms of dosage. In 29 (14%) patients, the comedications required monitoring when used with ELB/GZR, as well as with all available DAAs. Of the 190 drugs, 27 (14%) used in 67% of patients were free of DDIs when used with ELB/GZR, whereas they required monitoring if used with other DAA regimens. CONCLUSIONS: The results of this prospective study support findings that ELB/GZR is effective and safe in most treated patients.
Short-term neuropsychiatric tolerability of bictegravir combined with emtricitabine/tenofovir alafenamide in clinical practice.
Hoffmann C, Schewe K, Fenske S … +5 more , Buhk T, Sabranski M, Adam A, Hansen S, Stellbrink HJ
Antivir Ther · 2020 · PMID 32235038 · Publisher ↗
BACKGROUND: Neuropsychiatric AEs (NPAEs) leading to dolutegravir (DTG) discontinuation were seen more frequently in real-world use than in randomized clinical trials (RCTs). The recently approved fixed-dose combination b...
BACKGROUND: Neuropsychiatric AEs (NPAEs) leading to dolutegravir (DTG) discontinuation were seen more frequently in real-world use than in randomized clinical trials (RCTs). The recently approved fixed-dose combination bictegravir plus emtricitabine and tenofovir alafenamide (BIC/F/TAF) has shown comparable NPAE rates but some favourable patient-reported outcomes in RCTs compared with DTG. We were interested in its neuropsychiatric tolerability in clinical practice. METHODS: All patients starting BIC/F/TAF from June 2018 in a single centre (two subcentres) were followed retrospectively. Discontinuation rates due to any AEs and NPAEs were compared with those of patients initiating DTG-based regimens. RESULTS: As of May 2019, a total of 943 patients (852 males, 76 females, 15 transgender and gender diverse) initiated BIC/F/TAF outside RCTs. After a median follow-up of 6.2 months, 50 (5.3%) and 31 (3.3%) patients had discontinued BIC/F/TAF due to any AEs or to NPAEs, respectively. In multivariate analysis, a pre-existing depression and subcentre remained predictive for NPAEs, but not age, gender, ethnicity or prior DTG-related AEs. Compared with 1,043 patients treated with DTG-based regimens, the estimated NPAE-related discontinuation rate with BIC/F/TAF was comparable during the first 6 months (P=0.36). Cross-intolerance was low, and only 5/55 patients with prior DTG intolerability had to discontinue BIC/F/TAF due to NPAEs. CONCLUSIONS: Short-term tolerability of BIC/F/TAF was comparable to DTG-containing regimens. As seen with DTG, discontinuation rates were higher than in RCTs. A pre-existing depression but also physician's awareness may have an impact on tolerability and continuation of BIC/F/TAF. In contrast, prior intolerability of DTG was of limited predictive value.
Differences in social and mental well-being of long-term survivors among people who inject drugs and other participants in the Swiss HIV Cohort Study: 1980-2018.
Kusejko K, Marzel A, Nguyen H … +17 more , Chaudron SE, Bachmann N, Weber R, Bruggmann P, Roth JA, Bernasconi E, Calmy A, Cavassini M, Bregenzer A, Böni J, Yerly S, Klimkait T, Perreau M, Walti LN, Günthard HF, Kouyos RD, Swiss HIV Cohort Study
Antivir Ther · 2020 · PMID 32235037 · Publisher ↗
BACKGROUND: People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a...
BACKGROUND: People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a particularly vulnerable population. We study social, clinical and mental factors of LTS in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID). METHODS: We quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. Using phylogenetic methods, we distinguished between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis. RESULTS: Overall, 1,663 of 5,686 (29.2%) PWID were LTS. We found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; P<0.001), incarceration (30.6% versus 7.0%; OR=6.9; P<0.001) and full work ability (25.4% versus 59.0%; OR=0.27; P<0.001). ClusteredHET were less vulnerable with respect to these variables than PWID LTS but more at risk compared with MSM/HETnc LTS, indicating that clusteredHET are closer to PWID with regard to social and mental aspects compared with all MSM/HETnc. CONCLUSIONS: Even more than 15 years post HIV diagnosis, special care for HIV-positive PWID is needed, with emphasis on mental health and social integration of PWID LTS.
Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.
Arenas-Pinto A, Stöhr W, Khoo S … +12 more , Clarke A, Beeching N, Warwick Z, Lee V, Else L, Wiggins R, Ferns B, Nastouli E, Dunn D, Lacey CJ, Paton NI, Protease Inhibitor monotherapy Versus Ongoing Triple therapy (PIVOT) Genital Secretion sub-study Team†
Antivir Ther · 2020 · PMID 32202510 · Publisher ↗
BACKGROUND: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monothe...
BACKGROUND: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono). METHODS: We measured HIV RNA and PI drug concentrations in samples of semen, cervico-vaginal and rectal mucosa secretions, and plasma in patients after 48-96 weeks on PI-mono or standard triple therapy. RESULTS: A total of 85 participants were recruited. Of the 43 participants on PI-mono (70% on darunavir [DRV]/ritonavir [r]), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, five had detectable virus in semen or vaginal secretions (HIV RNA >50 copies/ml in one), none in rectal mucosa and one in plasma. The median (IQR) concentration of DRV and atazanavir in semen (659.7 [339-1,089] and 128.8 [63-368] ng/ml, respectively) and cervico-vaginal samples (2,768 [312-7,879] and 1,836 [359-3,314] ng/ml, respectively) exceeded their protein adjusted median inhibition concentration (MIC). DRV concentration in rectal secretions showed higher variability compared with concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4, IQR 2.6-68.7:1). CONCLUSIONS: We found no substantive evidence of HIV shedding in patients taking PI-mono, suggesting that PIs provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.
Transmitted, pre-treatment and acquired antiretroviral drug resistance among men who have sex with men and transgender women living with HIV in Nigeria.
Crowell TA, Kijak GH, Sanders-Buell E … +14 more , O'Sullivan AM, Kokogho A, Parker ZF, Lawlor J, Polyak CS, Adebajo S, Nowak RG, Baral SD, Robb ML, Charurat ME, Ake JA, Ndembi N, Tovanabutra S, TRUST/RV368 Study Group
Antivir Ther · 2019 · PMID 32125280 · Full text
BACKGROUND: Across sub-Saharan Africa, men who have sex with men (MSM) and transgender women (TGW) have disproportionately poor HIV treatment outcomes. Stigma and criminalization create barriers to health-care engagement...
BACKGROUND: Across sub-Saharan Africa, men who have sex with men (MSM) and transgender women (TGW) have disproportionately poor HIV treatment outcomes. Stigma and criminalization create barriers to health-care engagement and adherence to antiretroviral therapy (ART), potentially promoting the development of HIV drug resistance (HIVDR). We evaluated transmitted, pre-treatment and acquired HIVDR among MSM and TGW in Lagos and Abuja, Nigeria. METHODS: Adults with HIV RNA ≥1,000 copies/ml in the TRUST/RV368 cohort, including incident cases diagnosed via 3-monthly screening, underwent HIVDR testing using the Sanger sequencing method. Major mutations conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were identified from the 2017 IAS-USA list. World Health Organization surveillance drug resistance mutations (SDRMs) were identified in ART-naive participants. RESULTS: From March 2013 to June 2017, 415 participants with median age 24 (interquartile range [IQR] 21-27) years, CD4 T-cell count 370 (IQR 272-502) cells/mm, and HIV RNA 4.73 (IQR 4.26-5.15) log copies/ml underwent HIVDR testing. SDRMs were observed in 36 of 373 ART-naive participants (9.7%, 95% confidence interval [95% CI 6.8, 13.1%]), including 8 of 39 incident cases (20.5%, [95% CI] 9.3, 36.5%). Among 42 ART-experienced participants, NNRTI resistance was detected in 18 (42.9%, 95% CI 27.7, 59.0%) and NRTI resistance in 10 (23.8%, 95% CI 12.0, 39.4%). No PI resistance was detected. CONCLUSIONS: The high prevalence of transmitted and acquired drug resistance among Nigerian MSM and TGW living with HIV suggests the need for programmatic solutions to improve uninterrupted access to ART and timely switch to second-line regimens in cases of viral failure.
Pretreatment HIV drug resistance and treatment failure in non-Italian HIV-1-infected patients enrolled in ARCA.
Bavaro DF, Di Carlo D, Rossetti B … +12 more , Bruzzone B, Vicenti I, Pontali E, Zoncada A, Lombardi F, Di Giambenedetto S, Borghi V, Pecorari M, Milini P, Meraviglia P, Monno L, Saracino A
Antivir Ther · 2020 · PMID 32118584 · Publisher ↗
BACKGROUND: An increase in pretreatment drug resistance (PDR) to first-line antiretroviral therapy (ART) in low-income countries has been recently described. Herein we analyse the prevalence of PDR and risk of virologica...
BACKGROUND: An increase in pretreatment drug resistance (PDR) to first-line antiretroviral therapy (ART) in low-income countries has been recently described. Herein we analyse the prevalence of PDR and risk of virological failure (VF) over time among migrants to Italy enrolled in ARCA. METHODS: HIV-1 sequences from ART-naive patients of non-Italian nationality were retrieved from ARCA database from 1998 to 2017. PDR was defined by at least one mutation from the reference 2009 WHO surveillance list. RESULTS: Protease/reverse transcriptase sequences from 1,155 patients, mainly migrants from sub-Saharan Africa (SSA; 42%), followed by Latin America (LA; 25%) and Western countries (WE; 21%), were included. PDR was detected in 8.6% of sequences (13.1% versus 5.8% for B and non-B strains, respectively; P<0.001). 2.1% of patients carried a PDR for protease inhibitors (PIs; 2.1% versus 2.3%; P=0.893), 3.9% for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; 6.8% versus 2.1%; P<0.001) and 4.3% for non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs; 6.3% versus 3.1%; P=0.013). Overall, prevalence of PDR over the years remained stable, while it decreased for PIs in LA (P=0.021) and for NRTIs (P=0.020) among migrants from WE. Having more than one class of PDR (P=0.015 versus absence of PDR), higher viral load at diagnosis (P=0.008) and being migrants from SSA (P=0.001 versus WE) were predictive of VF, while a recent calendar year of diagnosis (P<0.001) was protective for VF. CONCLUSIONS: PDR appeared to be stable over the years in migrants to Italy enrolled in ARCA; however, it still remains an important cause of VF together with viral load at diagnosis.
In vitro anti-influenza activity of in silico repurposed candidate drug cycrimine.
Matejin S, Bukreyeva N, Radosevic D … +5 more , Sencanski M, Mantlo E, Veljkovic V, Glisic S, Paessler S
Antivir Ther · 2019 · PMID 32108589 · Publisher ↗
BACKGROUND: Due to the limitations of current antiviral therapies because of drug resistance and the emergence of new circulating viral strains, novel effective antivirals are urgently needed. Results of the previous dru...
BACKGROUND: Due to the limitations of current antiviral therapies because of drug resistance and the emergence of new circulating viral strains, novel effective antivirals are urgently needed. Results of the previous drug repurposing by virtual screening of DrugBank revealed the anticholinergic drug cycrimine as a possible inhibitor of the influenza virus infection. METHODS: In this study we examined the potential antiviral activity of cycrimine in vitro. RESULTS: The experimental results showed the anti-influenza activity of cycrimine against two different influenza A subtypes in cell culture. CONCLUSIONS: The findings of this study suggest cycrimine as a potential therapeutic agent for influenza.
The effect of tenofovir disoproxil fumarate on bone mineral density: a systematic review and meta-analysis.
Baranek B, Wang S, Cheung AM … +2 more , Mishra S, Tan DH
Antivir Ther · 2020 · PMID 32077867 · Publisher ↗
BACKGROUND: We conducted a systematic review and meta-analysis (CRD#42017070552) to quantify the impact of oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) on bone mineral density (BMD) and the risk of osteopor...
BACKGROUND: We conducted a systematic review and meta-analysis (CRD#42017070552) to quantify the impact of oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) on bone mineral density (BMD) and the risk of osteoporosis, low bone mass and fractures, among people taking it as pre-exposure prophylaxis (PrEP), HIV treatment and HBV treatment. METHODS: We searched MEDLINE and EMBASE for randomized controlled trials published from 1997-2018 reporting BMD, osteoporosis, low bone mass and/or fractures in treatment-naive patients taking compared with not taking TDF for 48 ±4 weeks. We pooled outcomes using DerSimonian random-effects models. RESULTS: Our search yielded 5,178 abstracts, representing 3,865 articles, with 25 meeting the inclusion criteria. TDF was associated with greater BMD decline when taken as PrEP (lumbar spine: mean difference [MD]=-0.82%, 95% CI=-1.28, -0.37%, I=38%; total hip: MD=-0.81%, 95% CI=-1.22, -0.40%, I=48%) and HIV treatment (lumbar spine: MD=-1.62%, 95% CI=-2.30, -0.95%, I=93%; total hip: MD=-1.75%, 95% CI=-2.08, -1.42%, I=83%; femoral neck: MD=-1.26%, 95% CI=-2.15, -0.38%, I=43%) in comparison to those not taking TDF. Eight studies reported on incident osteoporosis or low bone mass, with variable results. Pooled results from five PrEP studies showed that TDF was not associated with increased fractures compared with no PrEP (RR=1.12, 95% CI=0.752, 1.74, I=26%). CONCLUSIONS: TDF caused greater decreases in BMD than did comparators when used for all three indications and the magnitude of this decrease was larger for HIV treatment compared with PrEP. Fractures were not increased among PrEP patients. The clinically significant BMD decline caused by TDF and current expansion of PrEP use suggest attention to the adverse bone effects of TDF will increase in importance.
Clinical efficacy and safety in telbivudine- or tenofovir-treated hepatitis B e antigen-positive pregnant women.
Deng H, Liang S, Xu M … +9 more , Zhuo L, Gao H, Chen K, Shi Y, Li H, Jiao Q, Lin L, Lei Y, Liu H
Antivir Ther · 2020 · PMID 32049069 · Publisher ↗
BACKGROUND: Telbivudine (LdT) and tenofovir (TDF) are widely used in pregnant women to prevent vertical transmission; however, limited data are available on the differences in clinical efficacy and safety between the two...
BACKGROUND: Telbivudine (LdT) and tenofovir (TDF) are widely used in pregnant women to prevent vertical transmission; however, limited data are available on the differences in clinical efficacy and safety between the two drugs. METHODS: A total of 307 hepatitis B e antigen (HBeAg)-positive pregnant women with complete follow-up data were enrolled, the patients with alanine aminotransferase (ALT) levels <1×ULN at baseline were enrolled to cohort 1 for treatment from 28 ±4 weeks gestation to delivery, while ALT levels >1×ULN at baseline were enrolled to cohort 2 for treatment from 28 ±4 weeks gestation and continued after delivery. The clinical efficacy and safety was compared in LdT- and TDF-treated patients. In addition, 32 patients in cohort 1 were analysed for nucleoside analogue (NA)-related resistance mutations at baseline and after delivery. RESULTS: The results showed that HBV DNA levels were significantly lower at delivery than at baseline (P<0.001), but the decreases in HBV DNA, ALT, total bilirubin and total bile acid levels did not differ between the LdT- and TDF-treated patients at different time points (P>0.05) in the two cohorts. However, gastrointestinal adverse effects (vomiting) occurred more frequently in TDF-treated than LdT-treated patients (6.6% versus 0.0%; P=0.001). The results of NA-related resistance mutations analysis in cohort 1 revealed that short-term LdT or TDF treatment did not significantly change the NA-related resistance mutations (P>0.05). CONCLUSIONS: This study revealed that the clinical efficacy in LdT- or TDF-treated HBeAg-positive Chinese pregnant women is similar, and gastrointestinal adverse effects occurred more frequently in TDF-treated patients.
Molecular pathway of influenza pan-neuraminidase inhibitor resistance in an immunocompromised patient.
Abed Y, Schibler M, Checkmahomed L … +7 more , Carbonneau J, Venable MC, Fage C, Giannotti F, Goncalves AR, Kaiser L, Boivin G
Antivir Ther · 2019 · PMID 32031540 · Publisher ↗
BACKGROUND: Neuraminidase (NA) inhibitors (NAIs), including oseltamivir and zanamivir, play an important therapeutic role against influenza infections in immunocompromised patients. In such settings, however, NAI therapy...
BACKGROUND: Neuraminidase (NA) inhibitors (NAIs), including oseltamivir and zanamivir, play an important therapeutic role against influenza infections in immunocompromised patients. In such settings, however, NAI therapy may lead to the emergence of resistance involving mutations within the influenza surface genes. The aim of this study was to investigate the evolution of NA and haemagglutinin (HA) genes of influenza A(H1N1)pdm09 virus in an immunocompromised patient receiving oseltamivir then zanamivir therapies. METHODS: Nasopharyngeal swab (NPS) samples were collected between 27 January 2018 and 11 April 2018 from a haematopoietic stem cell transplant recipient. These include 10 samples collected either pre-therapy, during oseltamivir and zanamivir treatment as well as after therapy. The A(H1N1)pdm09 HA/NA genes were sequenced. The H275Y NA substitution was quantified by droplet digital RT-PCR assay. A(H1N1)pdm09 recombinant viruses containing HA mutations were tested by HA elution experiments to investigate in vitro binding properties. RESULTS: Oseltamivir rapidly induced the H275Y NA mutation which constituted 98.33% of the viral population after 15 days of oseltamivir treatment. The related HA gene contained S135A and P183S substitutions within the receptor-binding site. After a switch to zanamivir, 275H/Y and 119E/G/D mixed populations were detected. In the last samples, the double H275Y-E119G NA variant dominated with S135A and P183S HA substitutions. CONCLUSIONS: This report confirms that oseltamivir can rapidly induce the emergence of the H275Y substitution in A(H1N1)pdm09 viruses and subsequent switch to zanamivir can lead to additional substitutions at codon E119 resulting in multi-drug resistance. Such data additionally suggest a potential compensatory role for HA substitutions near the receptor binding site.
Confirmation of the drug-drug interaction potential between cobicistat-boosted antiretroviral regimens and hormonal contraceptives.
Majeed SR, West S, Ling KH … +2 more , Das M, Kearney BP
Antivir Ther · 2019 · PMID 31933482 · Publisher ↗
BACKGROUND: Cobicistat (COBI), a CYP3A inhibitor, is a pharmacokinetic enhancer that increases exposures of the HIV protease inhibitors (PIs) atazanavir (ATV) and darunavir (DRV). The potential drug interaction between C...
BACKGROUND: Cobicistat (COBI), a CYP3A inhibitor, is a pharmacokinetic enhancer that increases exposures of the HIV protease inhibitors (PIs) atazanavir (ATV) and darunavir (DRV). The potential drug interaction between COBI-boosted PIs and hormonal contraceptives, which are substrates of intestinal efflux transporters and extensively metabolized by CYP enzymes, glucuronidation and sulfation, was evaluated. METHODS: This was a Phase I, open-label, two cohort (n=18/cohort), fixed-sequence study in healthy females that evaluated the drug-drug interaction (DDI) between multiple-dose ATV+COBI or DRV+COBI and single-dose drospirenone/ethinyl estradiol (EE). DDIs were evaluated using 90% confidence intervals of the geometric least-squares mean ratios of the test (drospirenone/EE+boosted PI) versus reference (drospirenone/EE) using lack of DDI boundaries of 70-143%. Safety was assessed throughout the study. RESULTS: 29/36 participants completed the study. Relative to drospirenone/EE alone, drospirenone area under the plasma concentration versus time curve extrapolated to infinity (AUC) was 1.6-fold and 2.3-fold higher, and maximum observed plasma concentration (C) was unaltered, upon coadministration with DRV+COBI and ATV+COBI, respectively. EE AUC decreased 30% with drospirenone/EE + DRV+COBI and was unchanged with ATV+COBI + drospirenone/EE, relative to drospirenone/EE alone. Study treatments were generally well tolerated. The majority of adverse events were mild and consistent with known safety profiles of the compounds. CONCLUSIONS: Consistent with COBI-mediated CYP3A inhibition, drospirenone exposure increased following coadministration with COBI-containing regimens, with a greater increase with ATV+COBI. Thus, clinical monitoring for drospirenone-associated hyperkalaemia is recommended with DRV+COBI and ATV+COBI should not be used with drospirenone. Lower EE exposure with DRV+COBI may be attributed to inductive effects of DRV on CYP enzymes and/or intestinal efflux transporters (that is, P-gp) involved in EE disposition.
Pharmacokinetics of oral tenofovir disoproxil fumarate in pregnancy and lactation: a systematic review.
Bierhoff M, Smolders EJ, Tarning J … +8 more , Burger DM, Spijker R, Rijken MJ, Angkurawaranon C, McGready R, White NJ, Nosten F, van Vugt M
Antivir Ther · 2019 · PMID 31868655 · Publisher ↗
BACKGROUND: Tenofovir disoproxil fumarate (TDF), the oral prodrug of tenofovir (TFV), is advocated in pregnancy for prevention of mother-to-child transmission (PMCT) with failure of hepatitis B immunoglobulin and vaccina...
BACKGROUND: Tenofovir disoproxil fumarate (TDF), the oral prodrug of tenofovir (TFV), is advocated in pregnancy for prevention of mother-to-child transmission (PMCT) with failure of hepatitis B immunoglobulin and vaccination. The pharmacokinetics of TDF monotherapy for PMCT-HBV is important if deployment is to emulate the success of multiple antiretrovirals (ARVs) for PMCT-HIV in resource-constrained settings. METHODS: This systematic review followed a protocol and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We included studies that enrolled pregnant women who received oral TDF therapy as monotherapy or in combination with other ARVs: irrespective of the reason for receiving the drug (for example, HIV, HBV or pre-exposure prophylaxis); and reported pharmacokinetics. RESULTS: The area under the concentration-time curve (AUC), maximum plasma concentrations (C) and last measurable plasma concentration (C) of TFV were decreased in the second and third trimester compared with first trimester or post-partum. In none of the manuscripts was the non-pregnant HBV threshold of C of 300 ng/ml reached, but the 50% effective concentration (EC) of TFV is lower for treatment of HBV compared with HIV. The TFV concentration in breastfed infants was 0.03% of the recommended infant dose. CONCLUSIONS: Most knowledge of pharmacokinetics of TFV in pregnancy results from studies on HIV involving multiple ARVs. Increased TFV clearance occurred in the second and third trimester when optimal TFV concentrations are required to maximize suppression of HBV in the window before birth. Dose or duration adjustments will be better conceptualized with concurrent analysis of the pharmacokinetics of TFV monotherapy and hepatitis B pharmacodynamics in pregnancy.
Elevated risk of viral rebound on ART in migrants living in France: role of socioeconomic factors.
Abgrall S, Raho-Moussa M, Seng R … +6 more , Ghislain M, Matheron S, Pialoux G, Goujard C, Meyer L, ANRS CO9-COPANA study group†
Antivir Ther · 2019 · PMID 31868654 · Publisher ↗
BACKGROUND: In Western countries, viral rebound on antiretroviral therapy (ART) appears to occur more frequently in migrants. We aimed to assess the respective roles of socioeconomic factors and migration on viral reboun...
BACKGROUND: In Western countries, viral rebound on antiretroviral therapy (ART) appears to occur more frequently in migrants. We aimed to assess the respective roles of socioeconomic factors and migration on viral rebound in people living with HIV (PLHIV) in France. METHODS: We included PLHIV in France, enrolled from 2004 to 2008 in the French ANRS-COPANA cohort, who started a first ART and achieved undetectability (<50 copies/ml) within 1 year. Determinants of viral rebound were assessed using Cox models including geographical origin, HIV transmission group, and clinicobiological and sociodemographic data. RESULTS: Of 499 included individuals, 288 were born in France, 158 in sub-Saharan Africa (SSA) and 53 in another country. Kaplan-Meier probabilities of viral rebound-free survival were similar for men having sex with men (MSM) and heterosexuals born in France, and lower in migrants from SSA or other countries (P<0.001). The crude hazard ratio (HR) of viral rebound was 2.49 (95% CI, 1.59, 3.90) in migrants from SSA and 1.78 (0.94, 3.88) in migrants from other countries compared with MSM born in France. Educational level, financial difficulties and HIV status disclosure had the biggest impact on the difference between the crude and adjusted HRs for viral rebound in migrants. In multivariable analysis, viral rebound was no longer associated with geographical origin, but with protease inhibitor-containing ART, a VACS index ≥35 as a potential indicator of frailty, poor financial status (difficulties or debts) and non-disclosure to friend(s). CONCLUSIONS: Socioeconomic factors affect outcomes on ART, even in the context of free access to HIV care and treatment. Patient-centred strategies should be encouraged with the intervention of social workers to address basic needs and promote social support for more socially vulnerable individuals.
Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study.
Abreu RM, Bassit LC, Tao S … +8 more , Jiang Y, Ferreira AS, Hori PC, Ganova-Raeva LM, Khudyakov Y, Schinazi RF, Carrilho FJ, Ono SK
Antivir Ther · 2019 · PMID 31799942 · Full text
BACKGROUND: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients. METHODS: A prospective 183 Br...
BACKGROUND: Chronic hepatitis B (CHB) treatment adherence has been poorly studied worldwide. We evaluated long-term virological and adherence outcomes to antiviral treatment in CHB patients. METHODS: A prospective 183 Brazilian CHB patient cohort treated with monotherapy or combination adefovir dipivoxil, entecavir, lamivudine and/or tenofovir disoproxil fumarate was studied in a reference tertiary centre. Treatment adherence was evaluated by a validated questionnaire named 'Assessment of Adherence to Antiviral Therapy Questionnaire' (CEAT-HBV) within three yearly periods (2010/2011, 2013/2014 and 2014/2015). RESULTS: CEAT-HBV identified 43% (79/183) patients with non-adherence to antiviral treatment and among them, 67% (53/79) were viral load positive. The main causes associated with non-response to antiviral treatment were drug resistance variants followed by non-adherence, insufficient treatment duration and other causes. Single-dose pharmacokinetics demonstrated 35% (23/65) antiviral non-adherence. 2 years after the first assessment, the CEAT-HBV indicated that 71% (101/143) of subjects adhered to treatment (per-protocol population). However, 21% (40/183) of the patients could not be evaluated and were excluded. The main reasons for exclusion were death (20/183), 11 out 20 deaths due to hepatocellular carcinoma. HBV booklet was used for medical education. The third CEAT-HBV assessment (2014/2015) showed that 83% (112/135) patients were compliant with treatment adherence (per-protocol population). Long-term evaluation showed that adherence rate based on CEAT-HBV continue to increase after 4-years (P<0.001). CONCLUSIONS: The results highlight the importance of CHB therapy adherence assessment monitoring. Long-term adherence outcomes were dynamic and it is possible to increase the migration rate to adherence/HBV-DNA-negative group.
Low vitamin D is associated with coronary atherosclerosis in women with HIV.
Cheru LT, Saylor CF, Fitch KV … +5 more , Looby SE, Lu M, Hoffmann U, Stanley TL, Lo J
Antivir Ther · 2019 · PMID 31742564 · Full text
BACKGROUND: Vitamin D deficiency is underdiagnosed and undertreated, especially among people living with HIV (PLWH). Recently, there has been an increased interest in the role of vitamin D in cardiovascular disease (CVD)...
BACKGROUND: Vitamin D deficiency is underdiagnosed and undertreated, especially among people living with HIV (PLWH). Recently, there has been an increased interest in the role of vitamin D in cardiovascular disease (CVD). While vitamin D deficiency has been associated with CVD in observational studies in the general population, there are limited data in PLWH. We therefore performed an analysis to assess the relationship of vitamin D and coronary atherosclerosis using coronary CT angiography (CCTA). METHODS: Women living with HIV (WLWH) without known CVD were included. Based on the median value of serum vitamin D levels, participants were dichotomized to either the <25 ng/ml (lower vitamin D group) or ≥25 ng/ml (higher vitamin D group). CCTA was used to assess plaque characteristics. RESULTS: Forty-three WLWH were included in the analyses (mean age 46 ±8 years, 56% African American, duration of HIV 15 ±6 years, 83% undetectable HIV viral load). WLWH in the lower vitamin D group (n=22) had significantly higher numbers of segments with any coronary plaque (2.27 ±3.01 versus 0.38 ±0.97; P=0.02) and segments with non-calcified coronary plaque (1.41 ±1.82 versus 0.29 ±0.64; P=0.03) compared with WLWH in the higher vitamin D group (n=21). After adjusting for Framingham CHD risk point score, body mass index, diabetes and race, the relationship remained significant. CONCLUSIONS: Our study demonstrates a significant, independent relationship between lower vitamin D status and higher numbers of noncalcified coronary plaque segments in WLWH. Further studies are warranted to evaluate the effect of vitamin D on CVD in PLWH. Trial Registration Identifier: NCT00455793.
21st International Workshop on Co-morbidities and Adverse Drug Reactions in HIV.
Antivir Ther · 2019 · PMID 31697264
Abstract loading — click title to view on PubMed.
Abnormal QTc syndrome in HIV-infected patients: a systematic review of prevalence and risk factors.
Chastain DB, Veve MP, Wagner JL
Antivir Ther · 2019 · PMID 31570667 · Publisher ↗
BACKGROUND: The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac death (SCD) in persons living with HIV...
BACKGROUND: The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac death (SCD) in persons living with HIV (PLWH). METHODS: A systematic literature search using PubMed and Google Scholar databases was performed using the following search terms: 'HIV and prolonged QTc' and 'managing HIV-patients with prolonged QTc'. References within articles of interest were also evaluated. RESULTS/DISCUSSION: PLWH are at an increased risk of having a prolonged QTc interval. Some risk factors for this include the virus itself, concomitant medications, comorbid conditions, addictions and electrolyte disturbances. PLWH who have an increased HIV RNA viral load or decreased CD4 T-cell count are at further risk for progressing to sudden cardiac death (SCD). Many medications commonly prescribed in the PLWH population, such as antiretrovirals and antimicrobials used in opportunistic infection prophylaxis, have also been shown to promote QTc prolongation through inhibition of human ether-a-go-go potassium channels or through drug metabolism inhibition of other QTc prolonging drugs. CONCLUSIONS: Due to the high number of risk factors associated with QTc prolongation, clinicians should incorporate baseline and routine ECG monitoring for PLWH to potentially lower the increased risk of SCD in PLWH.
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