scholarly journals 301. Risk of Virologic Failure with Antiretroviral Switches in HIV/HCV Co-infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S162-S162
Author(s):  
Diana M Mosquera ◽  
Julius Wilder ◽  
Alicia Ellis ◽  
Susanna Naggie
Keyword(s):  
Treatment Failure ◽  
Virologic Failure ◽  
Sustained Viral Response ◽  
Composite Endpoint ◽  
Hiv Treatment ◽  
Transmission Risk ◽  
Research Network ◽  
Strand Transfer ◽  
Hcv Transmission ◽  
Switch Group

Abstract Background Direct-acting antivirals (DAA) and antiretroviral (ARV) medications pose treatment challenges in HIV/HCV co-infection. Management of contraindicated combinations varies across practices. ARV switches may increase the risk of HIV virologic and treatment failure, and has been reported to increase the risk of DAA treatment failure. This analysis assesses how switches in ARV regimen impacts treatment outcomes in HIV/HCV co-infection. Methods This retrospective cohort study includes patients 18 years and older with stable HIV/HCV co-infection (HIV RNA<50 for ≥6 months) who received DAA HCV therapy. Data were obtained using the Centers for AIDS Research Network of Integrated Clinical Systems. The “ARV switch” cohort is defined as patients undergoing a switch in ARV regimen within 6 months prior to DAA treatment. The “no ARV switch” cohort was defined as patients without a change in ARV during the same time period. The primary outcome is HIV treatment failure which is a composite endpoint including HIV virologic failure (defined as confirmed loss of HIV viral suppression), discontinuation/change of ARV regimen, progression to AIDS, or death. We compared baseline characteristics, the proportion of patients free of HIV treatment failure, free of HIV virologic failure, and that achieved sustained viral response (SVR) at 12 and 24 weeks after DAA treatment among ARV switch and no ARV switch groups. Results Of the 256 patients, 63/256 (25%) underwent an ARV switch (Table 1). At baseline, the most common regimen in the ARV switch group was protease inhibitor (PI)-based while for the no ARV switch group, it was an integrase strand transfer inhibitor (INSTI)-based regimen. HIV/HCV transmission risk factors, HCV genotype, and AST/ALT were similar among the two groups (Table 1). The proportion with HIV treatment and virologic failure, and the proportion achieving SVR12/24 were similar among the ARV switch and no ARV switch groups. Conclusion HIV treatment and virologic failure, and SVR12/24 were not different among patients who did or did not undergo a switch in their ARV regimen prior to DAA treatment. This suggests that switches in the ARV regimen for DAA treatment of HCV do not negatively impact HIV or HCV outcomes among patients with HIV/HCV Coinfection. Disclosures All authors: No reported disclosures.

scholarly journals Evolution in Real-World Therapeutic Strategies for HIV Treatment: A Retrospective Study in Southern Italy, 2014–2020

2021 ◽  
Vol 11 (1) ◽  
pp. 161
Author(s):  
Nunzia Papa ◽  
Simona Cammarota ◽  
Anna Citarella ◽  
Luigi Atripaldi ◽  
Francesca F. Bernardi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Real World ◽  
Treatment Guidelines ◽  
Virologic Failure ◽  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
Strand Transfer ◽  
Treatment Change ◽  
Hiv Patients ◽  
Treatment Naïve

Changes in HIV treatment guidelines over the last two decades reflect the evolving challenges in this field. Our study examined treatment change patterns throughout a 7-year period in a large Italian cohort of HIV patients as well as the reasons and direction of changes. Treatment-naïve and -experienced HIV patients managed by Cotugno Hospital of Naples between 2014 and 2020 were analyzed. During the period, the proportion of single-tablet regimen treatment sharply increased for the naïve and experienced patients. Regimens containing integrase strand transfer inhibitors rapidly replaced those containing protease inhibitor and non-nucleoside reverse transcriptase inhibitors. The use of the tenofovir alafenamide fumarate/emtricitabine backbone increased rapidly after its introduction in the Italian pharmaceutical market, making up 63.7 and 54.9% of all treatments in naïve and experienced patients, respectively, in 2020. The main reason for treatment changes was optimization and/or simplification (90.6% in 2018; 85.3% in 2019; 95.5 in 2020) followed by adverse effects and virological failure. Our real-world analysis revealed that the majority of treatment-naïve and treatment-experienced patients received antiretroviral drugs listed as preferred/recommended in current recommendations. Regimen optimization and/or simplification is a leading cause of treatment modification, while virologic failure or adverse effects are less likely reasons for modification in the current treatment landscape.

scholarly journals Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011–2017

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Volkan Korten ◽  
◽  
Deniz Gökengin ◽  
Gülhan Eren ◽  
Taner Yıldırmak ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Virologic Failure ◽  
Risk Function ◽  
Transcriptase Inhibitor ◽  
Cox Proportional Hazards ◽  
Antiretroviral Drugs ◽  
Competing Risk ◽  
First Year ◽  
Strand Transfer ◽  
Factors Associated

Abstract Background There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics. Methods A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models. Results The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0–6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1–6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4–0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05). Conclusion ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

scholarly journals 936. Evaluating the Impact of Polypharmacy on Virologic Success in People with HIV

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S501-S502
Author(s):  
Humberto R Jimenez ◽  
Naana Boachie ◽  
Sangwon Park ◽  
Jin Suh
Keyword(s):  
Hiv Transmission ◽  
Virologic Failure ◽  
Descriptive Analysis ◽  
Virologic Response ◽  
Transmission Risk ◽  
Pill Burden ◽  
Cross Sectional ◽  
Hiv Rna ◽  
Aids Diagnosis ◽  
The Impact

Abstract Background As people with HIV (PWH) have experienced reductions in antiretroviral pill burden, there has been an increase in medications to manage non-AIDS-related co-morbidities. Previous studies have linked virologic failure to an increased pill burden. This study assessed whether polypharmacy and other variables affect success of HIV management in our population. Methods A retrospective, cross-sectional analysis of PWH receiving care at a Ryan White-funded clinic in New Jersey was performed. Eligible patients were ≥18 years old, had ≥2 visits in 2019 and were receiving antiretroviral therapy (ART). The primary endpoints were to determine the effect polypharmacy (defined as 5 or more non-ART pills per day) on virologic response rates (HIV RNA &lt; 200 copies/mL). Secondary endpoints accounted for the impact of age, gender, race/ethnicity, HIV transmission risk factor, and AIDS diagnosis on virologic response. A descriptive analysis of comorbidities and medication classes was also completed. Logistic regression, chi square and student’s t test were used for statistical analysis. Results 964 patients were included in the analysis, with 355 (37%) meeting the criteria for polypharmacy. Most patients were male (60%) and the mean age was 49 years of age. The racial/ethnic breakdown was 46% Hispanic, 45% Black and 8% White. Polypharmacy was associated with higher rates of virologic success compared to those with a lower pill burden: 94% vs 86% had an HIV RNA &lt; 200 copies/mL (P=0.0003), respectively. ART pill burden was statistically, but not clinically higher among those with polypharmacy (1.34 vs 1.45, P=0.025). Virologic response was found to be higher among Hispanics and Whites in comparison to Black patients (OR 2.2, CI 1.4-3.5 and 3.0, CI 1.1-8.2). Patients with an AIDS diagnosis were less likely to achieve virologic response (OR 0.64, CI 0.42-0.99). Conclusion Patients with polypharmacy were more likely to achieve virologic success than paitents with a low pill burden in our population. Disclosures Humberto R. Jimenez, PharmD, BCPS, AAHIVP, Gilead (Speaker’s Bureau)

scholarly journals Analysis of Low-Frequency Mutations Associated with Drug Resistance to Raltegravir before Antiretroviral Treatment

2010 ◽  
Vol 55 (3) ◽  
pp. 1114-1119 ◽  
Author(s):  
Jia Liu ◽  
Michael D. Miller ◽  
Robert M. Danovich ◽  
Nathan Vandergrift ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Low Frequency ◽  
Hiv Treatment ◽  
Viral Population ◽  
Virologic Suppression ◽  
Resistance Mutations ◽  
The Difference ◽  
Allele Specific Sequencing ◽  
Hiv 1

ABSTRACTRaltegravir is highly efficacious in the treatment of HIV-1 infection. The prevalence and impact on virologic outcome of low-frequency resistant mutations among HIV-1-infected patients not previously treated with raltegravir have not been fully established. Samples from HIV treatment-experienced patients entering a clinical trial of raltegravir treatment were analyzed using a parallel allele-specific sequencing (PASS) assay that assessed six primary and six secondary integrase mutations. Patients who achieved and sustained virologic suppression (success patients,n= 36) and those who experienced virologic rebound (failure patients,n= 35) were compared. Patients who experienced treatment failure had twice as many raltegravir-associated resistance mutations prior to initiating treatment as those who achieved sustained virologic success, but the difference was not statistically significant. The frequency of nearly all detected resistance mutations was less than 1% of viral population, and the frequencies of mutations between the success and failure groups were similar. Expansion of pre-existing mutations (one primary and five secondary) was observed in 16 treatment failure patients in whom minority resistant mutations were detected at baseline, suggesting that they might play a role in the development of drug resistance. Two or more mutations were found in 13 patients (18.3%), but multiple mutations were not present in any single viral genome by linkage analysis. Our study demonstrates that low-frequency primary RAL-resistant mutations were uncommon, while minority secondary RAL-resistant mutations were more frequently detected in patients naïve to raltegravir. Additional studies in larger populations are warranted to fully understand the clinical implications of these mutations.

Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries

2021 ◽  
pp. sextrans-2020-054648
Author(s):  
Babatunde Akinwunmi ◽  
Daniel Buchenberger ◽  
Jenny Scherzer ◽  
Martina Bode ◽  
Paolo Rizzini ◽  
...  
Keyword(s):  
Unmet Needs ◽  
Resource Constraints ◽  
Hiv Treatment ◽  
Transmission Risk ◽  
People Living With Hiv ◽  
Privacy Concerns ◽  
Medical Needs ◽  
Suboptimal Adherence ◽  
Long Acting ◽  
Living With Hiv

ObjectivesA novel long-acting regimen (LAR) of cabotegravir and rilpivirine for HIV treatment requires dosing every 2 months instead of daily. We assessed what proportion of people living with HIV and physicians would be interested in trying and offering LAR respectively and why.Methods688 people living with HIV on treatment, and 120 HIV physicians completed web-based surveys in Germany, Italy, the UK and France during 2019. Balanced description of a hypothetical LAR regarding efficacy, administration and possible side effects were provided. The hypothetical long-acting injections were assumed to be cost-neutral to current daily oral antiretrovirals. Interest of people living with HIV in trying (‘very’/’highly’) and physicians’ willingness to offer (‘definitely’/’probably’) this LAR in different situations, with perceived benefits/concerns was measured.ResultsOf people living with HIV, 65.8% were interested in trying LAR. The majority (~80%–90%) of those with unmet needs felt LAR would help, including those with strong medical needs (malabsorption and interfering gastrointestinal conditions), suboptimal adherence, confidentiality/privacy concerns and emotional burden of daily dosing. Of physicians, percentage willing to offer LAR varied situationally: strong medical need (dysphagia, 93.3%; malabsorption, 91.6%; interfering gastrointestinal issues, 90.0%; central nervous system disorders, 87.5%); suboptimal adherence (84.2%); confidentiality/privacy concerns (hiding medications, 86.6%) and convenience/lifestyle (84.2%). People living with HIV liked LAR for not having to carry pills when travelling (56.3%); physicians liked the increased patient contact (54.2%). Furthermore, 50.0% of people living with HIV perceived LAR would minimise transmission risk and improve their sexual health. The most disliked attribute was scheduling appointments (37.2%) and resource constraints (57.5%) for people living with HIV and physicians, respectively. Physicians estimated 25.7% of their patients would actually switch.ConclusionProviders and people living with HIV viewed the described LAR as addressing several unmet needs. Alternative treatment routes and especially LAR may improve adherence and quality of life.

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections

Chemotherapy ◽  
2018 ◽  
Vol 63 (6) ◽  
pp. 345-351 ◽  
Author(s):  
Corey C. Burrelli ◽  
Eleanor K. Broadbent ◽  
Alice Margulis ◽  
Graham M. Snyder ◽  
Howard S. Gold ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Adverse Effects ◽  
Treatment Failure ◽  
Kidney Injury ◽  
Bloodstream Infections ◽  
Composite Endpoint ◽  
Acute Interstitial Nephritis ◽  
Beta Lactam ◽  
Significant Difference

Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. Conclusions: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

scholarly journals Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
María Eugenia Soria ◽  
Carlos García-Crespo ◽  
Brenda Martínez-González ◽  
Lucía Vázquez-Sirvent ◽  
Rebeca Lobo-Vega ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Treatment Failure ◽  
Antiviral Agents ◽  
Three Dimensional ◽  
Sustained Viral Response ◽  
Amino Acid Substitutions ◽  
Hepatitis C Virus Infection ◽  
Bona Fide

ABSTRACT Despite the high virological response rates achieved with current directly acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. The identification of amino acid substitutions associated with treatment failure requires analytical designs, such as subtype-specific ultradeep sequencing (UDS) methods, for HCV characterization and patient management. Using this procedure, we have identified six highly represented amino acid substitutions (HRSs) in NS5A and NS5B of HCV, which are not bona fide resistance-associated substitutions (RAS), from 220 patients who failed therapy. They were present frequently in basal and posttreatment virus of patients who failed different DAA-based therapies. Contrary to several RAS, HRSs belong to the acceptable subset of substitutions according to the PAM250 replacement matrix. Their mutant frequency, measured by the number of deep sequencing reads within the HCV quasispecies that encode the relevant substitutions, ranged between 90% and 100% in most cases. They also have limited predicted disruptive effects on the three-dimensional structures of the proteins harboring them. Possible mechanisms of HRS origin and dominance, as well as their potential predictive value for treatment response, are discussed.

scholarly journals Predictors of Hepatitis C Treatment Failure After Using Direct-Acting Antivirals in People Living With Human Immunodeficiency Virus

2019 ◽  
Vol 6 (3) ◽  
Author(s):  
Edward R Cachay ◽  
Alvaro Mena ◽  
Luis Morano ◽  
Laura Benitez ◽  
Ivana Maida ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mental Illness ◽  
Drug Use ◽  
Treatment Failure ◽  
Illicit Drug ◽  
Virologic Failure ◽  
Illicit Drug Use ◽  
Hcv Treatment ◽  
Immunodeficiency Virus ◽  
Direct Acting

Abstract Background Little is known about the influence of ongoing barriers to care in the persistence of hepatitis C virus (HCV) viremia after treatment with direct-acting antivirals (DAAs) among people living with human immunodeficiency virus (PLWH). Methods We conducted a retrospective cohort analysis of PLWH treated through the standard of care in 3 Western countries, to investigate the predictors of HCV treatment failure (clinical or virologic), defined as having a detectable serum HCV ribonucleic acid within 12 weeks after DAA discontinuation. In addition to HCV and liver-related predictors, we collected data on ongoing illicit drug use, alcohol abuse, mental illness, and unstable housing. Logistic regression analyses were used to identify predictors of HCV treatment failure. Results Between January 2014 and December 2017, 784 PLWH were treated with DAA, 7% (n = 55) of whom failed HCV therapy: 50.9% (n = 28) had a clinical failure (discontinued DAA therapy prematurely, died, or were lost to follow-up), 47.3% (n = 26) had an HCV virologic failure, and 1 (1.8%) was reinfected with HCV. Ongoing drug use (odds ratio [OR] = 2.60) and mental illness (OR = 2.85) were independent predictors of any HCV treatment failure. Having both present explained 20% of the risk of any HCV treatment failure due to their interaction (OR = 7.47; P &lt; .0001). Predictors of HCV virologic failure were ongoing illicit drug use (OR = 2.75) and advanced liver fibrosis (OR = 2.29). Conclusions People living with human immunodeficiency virus with ongoing illicit drug use, mental illness, and advanced liver fibrosis might benefit from enhanced DAA treatment strategies to reduce the risk of HCV treatment failure.

scholarly journals Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya

2020 ◽  
Vol 30 (1) ◽  
Author(s):  
Mabeya Sepha ◽  
Nyamache Anthony ◽  
Ngugi Caroline ◽  
Nyerere Andrew ◽  
Lihana Raphael
Keyword(s):  
Drug Resistance ◽  
Direct Sequencing ◽  
Integrase Inhibitor ◽  
Hiv Treatment ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Integrase Gene ◽  
Hiv 1

BACKGROUND: Antiretroviral therapy containing an integrase strand transfer inhibitor plus two Nucleoside Reverse Transcriptase inhibitors has now been recommended for treatment of HIV-1-infected patients. This thus determined possible pre-existing integrase resistance associated mutations in the integrase gene prior to introduction of integrase inhibitors combination therapy in Kenya.METHODS: Drug experienced HIV patients were enrolled at Kisii Teaching and Referral in Kenya. Blood specimens from (33) patients were collected for direct sequencing of HIV-1 polintegrase genes. Drug resistance mutations were interpreted according to the Stanford algorithm and phylogenetically analysed using insilico tools.RESULTS: From pooled 188 Kenyan HIV integrase sequences that were analysed for drug resistance, no major mutations conferring resistance to integrase inhibitors were detected. However, polymorphic accessory mutations associated with reduced susceptibility of integrase inhibitors were observed in low frequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%). Phylogenetic analysis (330 sequences revealed that HIV-1 subtype A1 accounted for majority of the infections, 26 (78.8%), followed by D, 5 (15.2%) and C, 2 (6%).CONCLUSION: The integrase inhibitors will be effective in Kenya where HIV-1 subtype A1 is still the most predominant. However, occurring polymorphisms may warrant further investigation among drug experienced individuals on dolutegravir combination or integrase inhibitor treatment. 

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