The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection

Paton, Nicholas I.; Stöhr, Wolfgang; Oddershede, Lars; Arenas‐Pinto, Alejandro; Walker, Simon; Sculpher, Mark; Dunn, David

doi:10.3310/hta20210

Cited by 15 publications

(18 citation statements)

References 84 publications

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“…This, however, does not have to translate into an alteration of the FG [23]. In our study, however, a slight decrease in mil/min of GFR during treatment with DRV/COBI was observed, at week 24 and 48.…”

Section: Discussioncontrasting

confidence: 75%

“…Secondly, the "pure ITT" or "switch-included" endpoint may have been interpreted differently across the studies -long-term follow-up after switching off randomized medication is essential for this endpoint to be collected. Thirdly, PIVOT trial [22,23] could not be included in the main analyses of efficacy, because the data had been presented using Kaplan-Meier curves, which were not consistent with the analyses of the other trials at fixed time-points.…”

Section: Discussionmentioning

confidence: 99%

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One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

Yunquera-Romero¹,

Diez²,

Rio-Valencia³

et al. 2017

J AIDS Clin Res

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IntroductionThe availability of antiretroviral treatment (ART) has made it possible to consider HIV-1 infection as a chronic disease. This has led to a change in the objectives of ART with a greater importance in improving the patient's quality of life and more efficient use of the resources, without compromising the effectiveness of treatments. In ART naive patients, on the first and successive lines after ART failure, preferred regimens remain the combination of three active drugs against HIV: Two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), a protease inhibitor (PI) with a pharmacokinetic (PK) enhancer (booster) (cobicistat or ritonavir), integrase strand transfer inhibitor (INSTI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) [1][2][3].Currently, boosted protease inhibitor monotherapy (PI/r): Darunavir/ritonavir (DRV/r) or Lopinavir/ritonavir (LPV/r) is only contemplated in the main treatment guidelines in pretreated patients to avoid toxicity associated with NRTIs, reduce costs and simplify ART. PI/r monotherapy with Atazanavir/ritonavir (ATV/r) is not recommended because of the worst results obtained in clinical trials. To initiate monotherapy based on PI/r, the patient must meet the following criteria: absence of chronic hepatitis B, plasma HIV-RNA viral load <50 copies/mL for at least 6 months and absence of mutations in the protease gene or virological failures (VF) prior to PI/r. PI/r are drugs that have a high genetic barrier and are used in monotherapy to maintain virological suppression in most patients, but with lower rates than triple therapy. The use of monotherapy with Lopinavir/ritonavir (LPV/r) and Darunavir/ritonavir (DRV/r) is associated with a higher frequency of "blips", defined as isolated and transient viral load values between 50 and <200 copies/mL. The "blips", although in most studies are not related to the increased risk of virological failure, do recommend re-evaluation of ART (degree of adhesion and genetic barrier) and in some patients may select resistant mutants [1]. Virological failure occurs when, in a patient with strict adherence and optimal tolerability to ART, there are any of the following two situations: a) Viral load detectable after 24 weeks of initiation of ART; B) if after reaching undetectability, th e viral load returns to >50 copies/mL in two consecutive determinations (separated by 2-4 weeks), excluding intercurrent vaccinations or infections (they may produce transient elevations of viral load). Virologic a l failure is AbstractIntroduction: Boosted protease inhibitor monotherapy (PI/r ) : Darunavir/ritonavir (DRV/r) or Lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pre-treated HIV patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTIs), reduce costs and simplify antiretroviral treatment. To start PI/r monotherapy, according to GESIDA g uidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, pla...

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

Yunquera-Romero¹,

Diez²,

Rio-Valencia³

et al. 2017

J AIDS Clin Res

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“…Histograms revealed that the cost data were right-skewed; therefore, gamma distribution was used. For QALYs, as suggested in a previous National Institute for Health Research Health Technology Assessment report, 67 decrement of QALY was originally predicted in the regression using a gamma distribution. Decrement of QALY was calculated as the difference between the maximum QALYs that could possibly be accrued within the time frame and the actual QALY gained.…”

Section: Discussionmentioning

confidence: 99%

Exercise- and strategy-based physiotherapy-delivered intervention for preventing repeat falls in people with Parkinson’s: the PDSAFE RCT

Ashburn

Pickering

McIntosh

et al. 2019

Health Technol Assess

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Background People with Parkinson’s disease are twice as likely to experience a fall as a healthy older person, often leading to debilitating effects on confidence, activity levels and quality of life. Objective To estimate the effect of a physiotherapy programme for fall prevention among people with Parkinson’s disease. Design A multicentre, pragmatic, investigator-masked, individually randomised controlled trial (RCT) with prespecified subgroup analyses. Setting Recruitment from NHS hospitals and clinics and community and social services in eight English regions with home-based interventions. Participants A total of 474 people with Parkinson’s disease (i.e. Hoehn and Yahr scale stages 1–4) were recruited: 238 were assigned to a physiotherapy programme and 236 were assigned to usual care. Random allocation was 50 : 50. Interventions All participants received routine care; the usual-care group received an information digital versatile disc (DVD) and a single advice session at trial completion. The intervention group had an individually tailored, progressive, home-based fall avoidance strategy training programme with balance and strengthening exercises: PDSAFE. Main outcome measures The primary outcome was the risk of repeat falling, collected by self-report monthly diaries between 0 and 6 months after randomisation. Secondary outcomes included near-falls, falls efficacy, freezing of gait (FoG), health-related quality of life, and measurements taken using the Mini-Balance Evaluation Systems Test (Mini-BESTest), the Chair Stand Test (CST), the Geriatric Depression Scale, the Physical Activity Scale for the Elderly and the Parkinson’s Disease Questionnaire. Results PDSAFE is the largest RCT of falls management among people with Parkinson’s disease: 541 patients were screened for eligibility. The average age was 72 years, and 266 out of 474 (56%) participants were men. Of the 474 randomised participants, 238 were randomised to the intervention group and 236 were randomised to the control group. No difference in repeat falling within 6 months of randomisation was found [PDSAFE group to control group odds ratio (OR) 1.21, 95% confidence interval (CI) 0.74 to 1.98; p = 0.447]. An analysis of secondary outcomes demonstrated better balance (Mini-BESTest: mean difference 0.95, 95% CI 0.24 to 1.67; p = 0.009), functional strength (CST: p = 0.041) and falls efficacy (Falls Efficacy Scale – International: mean difference 1.6, 95% CI –3.0 to –0.19; p = 0.026) with near-falling significantly reduced with PDSAFE (OR 0.67, 95% CI 0.53 to 0.86; p = 0.001) at 6 months. Prespecified subgroup analysis (i.e. disease severity and FoG) revealed a PDSAFE differing effect; the intervention may be of benefit for people with moderate disease but may increase falling for those in the more severe category, especially those with FoG. Limitations All participants were assessed at primary outcome; only 73% were assessed at 12 months owing to restricted funding. Conclusions PDSAFE was not effective in reducing repeat falling across the range of people with Parkinson’s disease in the trial. Secondary analysis demonstrated that other functional tasks and self-efficacy improved and demonstrated differential patterns of intervention impact in accordance with disease severity and FoG, which supports previous secondary research findings and merits further primary evaluation. Future work Further trials of falls prevention on targeted groups of people with Parkinson’s disease are recommended. Trial registration Current Controlled Trials ISRCTN48152791. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 36. See the NIHR Journals Library website for further project information. Sarah E Lamb is funded by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) at Oxford Health NHS Foundation Trust, the NIHR Oxford Biomedical Research Centre at the Oxford University Hospitals NHS Foundation Trust and CLAHRC Oxford. Victoria A Goodwin is supported by the NIHR Collaborations for Leadership in Applied Health Research and Care in the South West Peninsula (PenCLAHRC). Lynn Rochester is supported by the NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The research was also supported by the NIHR Newcastle Clinical Research Facility Infrastructure funding. Helen C Roberts is supported by CLAHRC Wessex and the NIHR Southampton Biomedical Research Centre.

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“…When QALY data were in a distribution with a left-skewed tail bounded by 0.5 QALYs (maximum QALYs accrued for a 6-month period), decrements of QALYs were predicted in the GLM regression with a gamma and log-link. The method of predicting decrements of QALYs was applied in a previous NIHR HTA report, 92 with decrements calculated as the difference between the maximum QALYs that could possibly be accrued within the time horizon of the analysis and the actual QALYs gained. This ensures that the QALY variable is right-skewed and left-bounded by 0, fitting into a gamma distribution.…”

Section: Discussionmentioning

confidence: 99%

A loyalty scheme to encourage physical activity in office workers: a cluster RCT

et al. 2019

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Background Increasing physical activity in the workplace can provide physical and mental health benefits for employees and economic benefits for the employer through reduced absenteeism and increased productivity. However, there is limited evidence on effective behaviour change interventions in workplace settings that led to maintained physical activity. This study aimed to address this gap and contribute to the evidence base for effective and cost-effective workplace interventions. Objectives To determine the effectiveness and cost-effectiveness of the Physical Activity Loyalty scheme, a multicomponent intervention based on concepts similar to those that underpin a high-street loyalty card, which was aimed at encouraging habitual physical activity behaviour and maintaining increases in mean number of steps per day. Design A cluster randomised controlled trial with an embedded economic evaluation, behavioural economic experiments, mediation analyses and process evaluation. Setting Office-based employees from public sector organisations in Belfast and Lisburn city centres in Northern Ireland. Participants A total of 853 participants [mean age 43.6 years (standard deviation 9.6 years); 71% of participants were female] were randomly allocated by cluster to either the intervention group or the (waiting list) control group. Intervention The 6-month intervention consisted of financial incentives (retail vouchers), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of the workplaces allowed participants to monitor their accumulated minutes of physical activity. Main outcome measures The primary outcome was mean number of steps per day recorded using a sealed pedometer (Yamax Digiwalker CW-701; Yamax, Tasley, UK) worn on the waist for 7 consecutive days and at 6 and 12 months post intervention. Secondary outcomes included health, mental well-being, quality of life, work absenteeism and presenteeism, and the use of health-care resources. Results The mean number of steps per day were significantly lower for the intervention group than the control group [6990 mean number of steps per day (standard deviation 3078) vs. 7576 mean number of steps per day (standard deviation 3345), respectively], with an adjusted mean difference of –336 steps (95% confidence interval –612 to –60 steps; p = 0.02) at 6 months post baseline, but not significantly lower at 12 months post baseline. There was a small but significant enhancement of mental well-being in the intervention group (difference between groups for the Warwick–Edinburgh Mental Wellbeing Scale of 1.34 points, 95% confidence interval 0.48 to 2.20 points), but not for the other secondary outcomes. An economic evaluation suggested that, overall, the scheme was not cost-effective compared with no intervention. The intervention was £25.85 (95% confidence interval –£29.89 to £81.60) more costly per participant than no intervention and had no effect on quality-adjusted life-years (incremental quality-adjusted life-years –0.0000891, 95% confidence interval –0.008 to 0.008). Limitations Significant restructuring of participating organisations during the study resulted in lower than anticipated recruitment and retention rates. Technical issues affected intervention fidelity. Conclusions Overall, assignment to the intervention group resulted in a small but significant decline in the mean pedometer-measured steps per day at 6 months relative to baseline, compared with the waiting list control group. The Physical Activity Loyalty scheme was deemed not to be cost-effective compared with no intervention, primarily because no additional quality-adjusted life-years were gained through the intervention. Research to better understand the mechanisms of physical activity behaviour change maintenance will help the design of future interventions. Trial registration Current Controlled Trials ISRCTN17975376. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 7, No. 15. See the NIHR Journals Library website for further project information.

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The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection

Cited by 15 publications

References 84 publications

One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

Exercise- and strategy-based physiotherapy-delivered intervention for preventing repeat falls in people with Parkinson’s: the PDSAFE RCT

A loyalty scheme to encourage physical activity in office workers: a cluster RCT

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