Patient-reported outcomes for HIV: the future of long-acting injectables and antiretroviral therapy evaluations

2021 ◽  
Author(s):  
Richard Leong ◽  
Leon Owusu ◽  
Jerrica Tang ◽  
Neeraj John ◽  
Kira E Voyer ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Treatment Satisfaction ◽  
Patient Reported Outcomes ◽  
Potential Role ◽  
Drug Regimen ◽  
Patient Reported ◽  
Immunodeficiency Virus ◽  
Long Acting ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Patient-reported outcomes (PROs) are an increasingly important aspect of patient care, as they offer a perspective from the patient themselves in the treatment and management of a particular disease state. They have a potential role in helping clinicians select an appropriate drug regimen in human immunodeficiency virus-1 (HIV-1)-infected individuals, as well as those with HIV/hepatitis C (HCV) co-infection. They can also provide insight for individuals receiving long-acting (LA) injectable antiretroviral therapy (ART). Studies found from PROs that participants on an LA injectable ART regimen reported greater preference and treatment satisfaction compared with those on an oral ART regimen. Some additional studies have also used PROs to evaluate the switch to single-tablet regimens and compare different ART in treating HIV-1. Current PROs and how they can be improved for LA injectables were also discussed.

scholarly journals 1035. Patient-Reported Outcomes on Long-Acting Cabotegravir + Rilpivirine as Maintenance Therapy: FLAIR 96-Week Results

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S548-S548
Author(s):  
Vasiliki Chounta ◽  
Enrique Bernal ◽  
Johan Lombaard ◽  
Harold P Katner ◽  
Sharon Walmsley ◽  
...  
Keyword(s):  
Treatment Satisfaction ◽  
Patient Reported Outcomes ◽  
Hiv Treatment ◽  
Virologic Suppression ◽  
Research Support ◽  
Treatment Groups ◽  
Patient Reported ◽  
The Difference ◽  
Long Acting ◽  
Hiv 1

Abstract Background In the phase 3 FLAIR study, switching to monthly injectable long-acting (LA) cabotegravir (CAB) + rilpivirine (RPV) was noninferior to continued daily oral dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) for the maintenance of virologic suppression over 96 weeks in adults with HIV-1. Key patient-reported outcomes (PROs) through Week 96 are presented. Methods In FLAIR, ART-naive adult participants received induction therapy with oral DTG/ABC/3TC for 20 weeks. Those with HIV-1 RNA < 50 c/mL at 16 weeks were randomized (1:1) to continue DTG/ABC/3TC or receive monthly CAB + RPV LA injections after a 4-week lead-in with daily oral CAB + RPV through Week 96. Treatment satisfaction (HIV Treatment Satisfaction Questionnaire status version [HIVTSQs]) and acceptability of injections (Perception of Injection [PIN] Questionnaire) up to Week 96 were secondary endpoints. Results A total of 566 participants were randomized (median age, 34 years; 22% female); baseline characteristics were similar between treatment groups. At Week 96, significantly greater improvement from baseline in total treatment satisfaction score was observed in the CAB + RPV LA vs DTG/ABC/3TC treatment group (adjusted mean difference, 2.3 [95% CI, 1.1-3.5]; P< 0.001), further increasing from Weeks 24 (2.1 [0.9-3.3]) and 44 (0.7 [−0.4, 1.9]). Key drivers for the difference in HIVTSQs between treatment groups were items assessing convenience, flexibility, and satisfaction to continue with LA therapy. In participants receiving CAB + RPV LA, mean score for the “Acceptability of ISRs” dimension of PIN (scale, 1-5) significantly decreased (improved) from Week 5 to Weeks 41, 48, and 96 (2.08 to 1.71, 1.66, and 1.71, respectively; P< 0.001 for all). In addition, 82% and 85% of LA participants, respectively, rated pain and local reactions due to injections as “totally” or “very acceptable” at Week 96. Conclusion At Week 96, FLAIR participants receiving LA therapy reported greater improvement in treatment satisfaction compared with participants continuing on daily oral medication as well as overall good acceptability of injections with improvement over time. Overall, these results support monthly CAB + RPV LA as an alternative to daily oral regimens for adults with HIV-1. Disclosures Vasiliki Chounta, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sharon Walmsley, FRCPC, MD, MSC, GSK (Grant/Research Support)ViiV Healthcare (Grant/Research Support) David Dorey, MMATH, GlaxoSmithKline Inc. (Employee, Shareholder) William Spreen, PharmD, ViiV Healthcare (Employee, Shareholder) Sandy Griffith, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) David Margolis, MD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

scholarly journals 2484. Patient Reported Outcomes After Switching to a 2-Drug Regimen of Dolutegravir + Rilpivirine: Week 148 Results from the Sword-1 and Sword-2 Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S861-S861
Author(s):  
Alan Oglesby ◽  
Kostas Angelis ◽  
Yogesh Punekar ◽  
Vasiliki Chounta ◽  
Antonio Antela ◽  
...  
Keyword(s):  
Health Status ◽  
Treatment Satisfaction ◽  
Patient Reported Outcomes ◽  
Symptom Burden ◽  
Drug Regimen ◽  
Virologic Suppression ◽  
Symptom Bother ◽  
Alternative Treatment Option ◽  
Maximum Utility ◽  
Patient Reported

Abstract Background The SWORD-1 and SWORD-2 studies previously demonstrated that high rates of virologic suppression were maintained for 148 weeks after switching virologically suppressed HIV-1 infected adults from their current 3- or 4-drug antiretroviral regimen (CAR) to the 2-drug regimen (2DR) of dolutegravir + rilpivirine on Day 1 (Early Switch (ES) DTG+RPV group). This abstract reports the pooled SWORD-1/2 results of patient reported outcomes (PRO) measures through Week 148. Methods HIV Treatment Satisfaction Questionnaire (HIVTSQ) and Symptom Distress Module (SDM) were secondary PRO endpoints in the SWORD trials. For HIVTSQ, high scores represent greater treatment satisfaction (range 0 to 60). SDM was assessed using the Symptom Bother Score with low values indicating less symptom bother (range 0 to 80). The EQ-5D-5L measure of general health status was assessed as an exploratory endpoint with maximum utility score of 1 to indicate perfect health. Change from Baseline in these endpoints was calculated for the ES subjects (over 148 weeks). Subjects randomized to CAR switched to DTG+RPV at Week 52 (Late Switch (LS) DTG+RPV group) and change from LS Baseline (i.e., last pre-switch assessment) was calculated (over 96 weeks). Results Low Symptom Bother (9.6 and 10.3) and high TSQ scores (54.4 and 54.3) were reported pre-switch in the ES and LS groups, respectively. ES subjects reported modest improvements from Baseline in both symptom burden and overall treatment satisfaction in all visits through Week 148 (Figures 1 and 2). Among the LS group, there was little change in symptom burden but similar improvement in treatment satisfaction. Pre-switch health status was high in ES and LS groups (EQ-5D mean utility: 0.96 and 0.94, respectively) and remained stable in both groups at all time points. Conclusion High treatment satisfaction and low symptom burden that were observed in patients under CAR were maintained long term after switching to DTG+RPV. These results corroborate DTG+RPV as a well-tolerated 2DR alternative treatment option in patients currently suppressed on other 3/4-drug regimens without previous virologic failure. Disclosures All authors: No reported disclosures.

scholarly journals Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Daniel O. Griffin ◽  
Michael Metzger ◽  
Kaitlin Poeth ◽  
Kathy Deng ◽  
Arif Dharsee ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
B Cell ◽  
Highly Active Antiretroviral Therapy ◽  
B Cell Lymphomas ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1 ◽  
Hiv Negative

Abstract Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival of <2 months from time of diagnosis.

scholarly journals Association of Male Sex and Obesity With Residual Plasma Human Immunodeficiency Virus 1 Viremia in Persons on Long-Term Antiretroviral Therapy

2020 ◽  
Author(s):  
Joshua C Cyktor ◽  
Ronald J Bosch ◽  
Hanna Mar ◽  
Bernard J Macatangay ◽  
Ann C Collier ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Single Copy ◽  
Normal Weight ◽  
Virologic Suppression ◽  
Residual Viremia ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Abstract Background Although adipose tissue has been proposed to harbor part of the human immunodeficiency virus 1 (HIV-1) reservoir, the influence of host characteristics, including sex and body mass index (BMI), on measures of HIV-1 persistence during antiretroviral therapy (ART) are incompletely understood. Methods We evaluated age, sex, BMI, waist circumference, years on ART, pre-ART HIV-1 RNA, pre-ART CD4+ T-cell count, and initial ART regimen with measures of HIV-1 persistence in blood (residual viremia, cellular HIV-1 DNA and RNA) in a cohort of 295 individuals with well-documented long-term virologic suppression (HIV-1 RNA <50 copies/mL) on ART (AIDS Clinical Trials Group study A5321). Results Men were more likely than women to have detectable plasma HIV-1 RNA by single-copy assay (52% vs 29%; P = .003), and the proportion of participants with detectable residual viremia increased in a stepwise fashion by BMI category (normal weight or underweight, 38%; overweight, 50%; and obese, 55%). ART regimen type was not associated with measures of HIV-1 persistence after controlling for ART duration. Conclusions Sex and obesity are independently associated with residual viremia in people on long-term ART. Additional studies to confirm these relationships and to define the mechanisms by which sex and obesity affect HIV-1 persistence are needed to inform HIV-1 cure strategies.

scholarly journals Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1798
Author(s):  
Grant R. Campbell ◽  
Stephen A. Spector
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Functional Cure ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.

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