scholarly journals Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Kristen E Ellis ◽  
George T Nawas ◽  
Connie Chan ◽  
Lawrence York ◽  
Julia Fisher ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Medical Records ◽  
Medication History ◽  
Hiv Rna ◽  
Persons Living With Hiv ◽  
Dosing Frequency ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Over Time

Abstract Background Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic. Methods Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the effect of ART switch on HIV RNA over time. Results Eighty-three PWH had DNA GT performed, 66 (80%) switched ART, and 59 had postswitch follow-up. Data were analyzed pre-/postswitch for these 59 PWH (median age, 54 years; 71% LWH ≥10 years; 46% ≥2 previous regimens; 36% recent low-level viremia; 34% unknown medication history). On DNA GT, 58% had ≥1-class ART resistance, 34% ≥2-class, and 10% 3-class. Median follow-up (range) was 337 (34–647) days. There was no change in probability of HIV RNA ≥50 copies/mL over time (P > .05). At baseline, 76% had HIV RNA <50 vs 88% at last postswitch follow-up (P = .092). Protease inhibitor use decreased from 58% to 24% (P < .001). Average daily pills and dosing frequency decreased from 3.48 to 2.05 (P < .001) and 1.39 to 1.09 (P < .001), respectively; ART cost did not change. Conclusions DNA GT facilitated changes in ART in a treatment-experienced population without increases in HIV RNA. Decreased pill burden occurred without increased ART cost. Further studies to identify optimal use of DNA GT are needed.

scholarly journals 1036. Persistence of Guideline-Recommended Antiretroviral Therapy Regimens among Persons Living with HIV Newly Initiating Treatment in the US

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S548-S549
Author(s):  
Joshua P Cohen ◽  
Xingzhi Wang ◽  
Rolin L Wade ◽  
Helena Diaz Cuervo ◽  
Dionne M Dionne
Keyword(s):  
Antiretroviral Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Treatment Discontinuation ◽  
Forest Plot ◽  
Current Guideline ◽  
First Line ◽  
Persons Living With Hiv ◽  
Living With Hiv

Abstract Background Discontinuation of first-line antiretroviral therapy (ART) may lead to poor outcomes for persons living with HIV (PLWH). While single-tablet regimens (STRs) have been associated with greater persistence compared to multi-tablet regimens (MTRs), few real-world studies have assessed persistence with current guideline-recommended ART regimens. The study aims to assess persistence among treatment-naïve PLWH initiating guideline-recommended ART regimens Methods Longitudinal pharmacy claims were extracted from IQVIA’s US LRx database for PLWH initiating ART between Jan 1, 2016 - Jul 31, 2019 (index period), with the observational period up to Jan 31, 2020. Index date was defined as the date of the first ART claim for STRs, or the date of the last filled drug of 1st set of claims for MTRs. Persistence was measured as the number of days until treatment discontinuation (≥ 90-day gap in therapy) and presented via Kaplan-Meier curves. Risk of discontinuation was assessed via Cox proportional hazards models, with BIC/FTC/TAF used as the reference ART regimen. Results Overall, 90,949 PLWH initiated STRs and 20,737 initiated MTRs. Average (SD) age was 43 (14) years, 75% were male, and 75% had commercial insurance. At 6 months of follow-up, 71% of PLWH initiating STRs and 56% initiating MTRs remained on their ART regimen. The proportion remaining on their index regimen at 6 months of follow-up was 79% for BIC/FTC/TAF, 73% for EVG/COBI/FTC/TAF, 71% for DTG/ABC/3TC, 69% for DTG + FTC/TAF, 67% for EFV/FTC/TDF, 62% for EVG/COBI/FTC/TDF, and 38% for DTG + FTC/TDF. Risk of discontinuation was higher for MTRs compared to STRs (hazard ratio [HR]: 1.63, 95% CI: 1.61 - 1.66). Compared to the referent BIC/FTC/TAF, risk of discontinuation was higher for EVG/COBI/FTC/TAF (HR: 1.54, 95% CI: 1.48 - 1.60), DTG/ABC/3TC (HR: 1.58, 95% CI: 1.52, 1.65), DTG + FTC/TAF (HR: 1.83, 95% CI: 1.74 - 1.93), EFV/FTC/TDF (HR: 2.31, 95% CI: 2.21 - 2.41), EVG/COBI/FTC/TDF (HR: 2.58, 95% CI: 2.47 - 2.70), and DTG + FTC/TDF (HR: 6.20, 95% CI: 5.83 - 6.59). Table 1. Persistence with ART by regimen for STR and MTR Figure 1. Forest Plot of Hazard Ratios for Treatment Discontinuation Conclusion Among US adult PLWH, STRs were associated with longer persistence on first-line therapy compared to MTRs. Among STRs, persistence was highest for BIC/FTC/TAF. Disclosures All Authors: No reported disclosures

scholarly journals 1022. Impact of Hospitalization on Antiretroviral Therapy for People Living with HIV

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S541-S541
Author(s):  
Amber Ladak ◽  
Henry N Young ◽  
Emily Tang ◽  
Jessica Curtis ◽  
Daniel B Chastain
Keyword(s):  
Antiretroviral Therapy ◽  
Primary Objective ◽  
Transitions Of Care ◽  
Specific Factor ◽  
People Living With Hiv ◽  
Hiv Rna ◽  
Patient Status ◽  
Persons Living With Hiv ◽  
Regimen Modification ◽  
Living With Hiv

Abstract Background Persons living with HIV (PLWH) are frequently hospitalized for reasons often unrelated to HIV. Transitioning of antiretroviral therapy (ART) while inpatient may not always be an immediate priority due to lack of knowledge, formulary restrictions, and patient status. This could lead to medication errors and gaps in therapy, which can persist at discharge, and could lead to viral rebound and disease progression. The purpose of this study was to identify effects of hospitalization on ART for PLWH. Methods This was an IRB approved, multi-center, retrospective cohort study of patients with HIV and/or AIDS based on ICD codes. Patients were included if they were at least 18 years old, receiving outpatient ART prior to admission, and hospitalized between March 2016 and March 2018. Patients were excluded if they were pregnant and only received intravenous zidovudine during their hospitalization. The primary objective was to determine the rate of ART restarted during hospitalization. Secondary objectives included rate at which inpatient ART was modified compared to outpatient regimen, and risk factors associated with regimen modification. Results Of 400 patients screened, 295 (74%) patients were on an outpatient ART regimen and were included in the study. Approximately half, 51%, were on a single tablet regimen (STR) outpatient. This population was majority male (59%) and of black race (87%). Median age was 49 years. Median CD4 count was 160 cells/mm3, while median HIV RNA for those with detectable viral load was 57,095 copies/mL. 236 of 295 patients (80%) received ART during their inpatient stay. However, 70 (30%) of these patients received a regimen that differed from their outpatient ART regimen. 69% of regimens were modified for reasons other than to optimize therapy. Patient sex, place of admission, and receipt of a STR or multi-tablet regimen (MTR) as an outpatient did not significantly impact rate of regimen modification. Conclusion Ensuring appropriate transition of ART during hospitalization remains an area in need of improvement. No one specific factor was associated with whether outpatient ART was appropriately and accurately restarted during hospitalization. Thus, there are many opportunities to improve transitions of care and antiretroviral stewardship. Disclosures All Authors: No reported disclosures

scholarly journals Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African Cohort Study

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Emmanuel Bahemana ◽  
◽  
Allahna Esber ◽  
Nicole Dear ◽  
Kavitha Ganesan ◽  
...  
Keyword(s):  
Cohort Study ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Cd4 Count ◽  
Age Group ◽  
Art Initiation ◽  
Living With Hiv ◽  
Over Time

Abstract Introduction With increased use of antiretroviral therapy (ART), HIV mortality rates are declining and people living with HIV (PLWH) are surviving longer. We characterized CD4 recovery and viral suppression among adults aged < 50 and ≥ 50 years living with HIV who initiated ART in the African Cohort Study (AFRICOS). Methods Beginning in January 2013, PLWH at twelve clinics in Kenya, Uganda, Tanzania and Nigeria underwent medical history review, CD4 and viral load testing as part of the ongoing African Cohort Study (AFRICOS). ART-naïve PLWH who initiated ART within 30 days of enrollment and had at least one year of follow-up were included in these analyses. To compare ART response in participants < 50 years and ≥ 50 years old, changes in CD4 count and viral load suppression after ART initiation were examined at different time points using linear and binomial regression with generalized estimating equations. Variables for time since ART initiation and the interaction between age group and time on ART were included in the model to evaluate longitudinal changes in CD4 recovery and viral suppression by age. Results Between January 2013 and September 2019, 2918 PLHV were enrolled in the cohort. Of these, 443 were ART naïve and initiated on ART within 30 days of enrollment, with 90% (n = 399) aged < 50 years old at ART initiation. At ART initiation, participants aged 50 and older had a higher median CD4 count compared to participants younger than 50 years of age although it did not reach statistical significance (306 cells/mm3, IQR:130–547 vs. 277cells/mm3, IQR: 132–437). In adjusted models examining CD4 recovery and viral suppression there were no significant differences by age group over time. By the end of follow-up viral suppression was high among both groups of adults (96% of adults ≥ 50 years old and 92% of adults < 50 years old). Conclusion This study found no difference in long-term CD4 recovery or viral suppression by age at ART initiation. We found that particularly among younger adults participants had lower median CD4 counts at ART initiation, suggesting the importance of identifying and putting this population on treatment earlier in the disease course.

scholarly journals Same-Day Associations Between Substance Use and Medication Nonadherence Among Persons Living with HIV

2019 ◽  
Vol 13 ◽  
pp. 117822181987875
Author(s):  
Susan E. Ramsey ◽  
Evan G. Ames ◽  
Julia Uber ◽  
Samia Habib ◽  
Seth Clark ◽  
...  
Keyword(s):  
Substance Use ◽  
Antiretroviral Therapy ◽  
Drug Use ◽  
Heavy Drinking ◽  
Art Adherence ◽  
Medication Nonadherence ◽  
Persons Living With Hiv ◽  
Objectively Measured ◽  
Living With Hiv

Objectives: To examine the same-day associations between substance use and objectively measured antiretroviral therapy (ART) nonadherence among persons living with HIV (PLWH). Methods: PLWH ( N = 53) were given an electronic pill box (EPB), and their ART adherence was monitored for 14 days. During a follow-up interview, participants were asked about any alcohol or drug use that occurred during those same 14 days. Results: Daily heavy drinking (⩾5 drinks for males and ⩾4 drinks for females) was associated with a nearly five times greater likelihood of same-day ART nonadherence (OR = 4.90, 95% CI = 1.79-13.36, P = .002). Further, drug use was associated with a nearly two times greater likelihood of ART nonadherence on the same day (OR = 1.80, 95% CI = 1.14-2.85, P = .012). Conclusions: These results highlight the importance of continuing to pursue interventions to effectively address heavy drinking and drug use among PLWH in order to improve ART adherence.

scholarly journals Decrease in Incidence Rate of Hospitalizations Due to AIDS-Defining Conditions but Not to Non-AIDS Conditions in PLWHIV on cART in 2008–2018 in Italy

2021 ◽  
Vol 10 (15) ◽  
pp. 3391
Author(s):  
Silvia Nozza ◽  
Laura Timelli ◽  
Annalisa Saracino ◽  
Nicola Gianotti ◽  
Claudia Lazzaretti ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Drug Users ◽  
Intravenous Drug Use ◽  
Hiv Rna ◽  
Persons Living With Hiv ◽  
History Of ◽  
Sex With Men ◽  
Living With Hiv ◽  
Italian Cohort

Background: We aimed to describe the change in the incidence and causes of hospitalization between 2008 and 2018 among persons living with HIV (PLWHIV) who started antiretroviral therapy (ART) from 2008 onwards in Italy. Methods: We included participants in the ICONA (Italian Cohort Naïve Antiretrovirals) cohort who started ART in 2008. All the hospitalizations occurring during the first 30 days from the start of ART were excluded. Hospitalizations were classified as due to: AIDS-defining conditions (ADC), non-ADC infections and non-infections/non-ADC (i.e., cardiovascular, pulmonary, renal-genitourinary, cancers, gastrointestinal-liver, psychiatric and other diseases). Comparisons of rates across time were assessed using Poisson regression. The Poisson multivariable model evaluated risk factors for hospitalizations, including both demographic and clinical characteristics. Results: A total of 9524 PLWHIV were included; 6.8% were drug users, 48.9% men-who-have sex with men (MSM), 39.6% heterosexual contacts; 80.8% were males, 42.3% smokers, 16.6% coinfected with HCV and 6.8% with HBV (HBsAg-positive). During 36,157 person-years of follow-up (PYFU), there were 1058 hospitalizations in 747 (7.8%) persons; they had HIV-RNA >50 copies mL in 34.9% and CD4 < 200/mmc in 27%. Causes of hospitalization were 23% ADC, 22% non-ADC infections, 55% non-infections/non-ADC (11% cancers; 9% gastrointestinal-liver; 6% cardiovascular; 5% renal-genitourinary; 5% psychiatric; 4% pulmonary; 15% other). Over the study period, the incidence rate (IR) decreased significantly (from 5.8 per 100 PYFU in 2008–2011 to 2.21 per 100 PYFU in 2016–2018). Age > 50 years, intravenous drug use (IDU), family history of cardiovascular disease, HIV-RNA > 50, CD4 < 200, were associated with a higher hospitalization risk. Conclusions: In our population of PLWHIV, the rate of hospitalization decreased over time.

scholarly journals 108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S183-S183
Author(s):  
Rajesh Gandhi ◽  
Joshua Cyktor ◽  
Ronald Bosch ◽  
Hanna Mar ◽  
Gregory Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Panel Member ◽  
Plasma Viremia ◽  
Research Support ◽  
Review Panel ◽  
Proviral Dna ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia ◽  
Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p&lt; 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

scholarly journals Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mayumi Imahashi ◽  
Hirotaka Ode ◽  
Ayumi Kobayashi ◽  
Michiko Nemoto ◽  
Masakazu Matsuda ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Strand Transfer ◽  
Intestinal Dysbiosis ◽  
Α Diversity ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1 ◽  
Over Time

AbstractIn HIV-1-infected patients, antiretroviral therapy (ART) is a key factor that may impact commensal microbiota and cause the emergence of side effects. However, it is not fully understood how long-term ART regimens have diverse impacts on the microbial compositions over time. Here, we performed 16S ribosomal RNA gene sequencing of the fecal and salivary microbiomes in patients under different long-term ART. We found that ART, especially conventional nucleotide/nucleoside reverse transcriptase inhibitor (NRTI)-based ART, has remarkable impacts on fecal microbial diversity: decreased α-diversity and increased ß-diversity over time. In contrast, dynamic diversity changes in the salivary microbiome were not observed. Comparative analysis of bacterial genus compositions showed a propensity for Prevotella-enriched and Bacteroides-poor gut microbiotas in patients with ART over time. In addition, we observed a gradual reduction in Bacteroides but drastic increases in Succinivibrio and/or Megasphaera under conventional ART. These results suggest that ART, especially NRTI-based ART, has more suppressive impacts on microbiota composition and diversity in the gut than in the mouth, which potentially causes intestinal dysbiosis in patients. Therefore, NRTI-sparing ART, especially integrase strand transfer inhibitor (INSTI)- and/or non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens, might alleviate the burden of intestinal dysbiosis in HIV-1-infected patients under long-term ART.

scholarly journals Effects of integrase inhibitor-based antiretroviral therapy on brain outcomes according to time since acquisition of HIV-1 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Prats ◽  
Ignacio Martínez-Zalacaín ◽  
Beatriz Mothe ◽  
Eugènia Negredo ◽  
Núria Pérez-Álvarez ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Integrase Inhibitor ◽  
Strand Transfer ◽  
Cognitive Differences ◽  
Integrase Strand Transfer Inhibitors ◽  
Initiation Of Therapy ◽  
Main Component ◽  
Living With Hiv ◽  
The Impact ◽  
Hiv 1

AbstractIntegrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.

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