Penta HIV Trials

13

Mar, 2020

Adeqaute dolutegravir exposure dosed BID with rifampicin in children 6 to < 18 years

 

Authors: Waalewijn H, Mujuru HA, Amuge P, Cotton M, Bollen P, Chan M, Ali S, Variavan E, Makumbi S, Colbers A, Gibb D, Ford D, Burger D, Turkova A, and the ODYSSEY-trial team

Published in27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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13

Mar, 2020

Adeqaute dolutegravir exposure dosed BID with rifampicin in children 6 to < 18 years

 

Authors: Waalewijn H, Mujuru HA, Amuge P, Cotton M, Bollen P, Chan M, Ali S, Variavan E,Makumbi S, Colbers A, Gibb D, Ford D, Burger D, Turkova A, and the ODYSSEY-trial team

Published in: Oral presentation at 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.

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14

Nov, 2019

Analysing small groups within clinical trials, while borrowing information from larger groups

 

Authors: Turner B, Ford D, Moore C, Gibb D, Turkova A,  White I, and ODYSSEY trial team

Published in: Oral Presentation atInternational Society for Clinical Biostatics; July 16th 2019

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14

Sep, 2019

Pharmacokinetics of dolutegravir 5mg dispersible tablets in children weighing 6 to <20kg dosed using WHO weight bands

 

Authors: Waalewijn H, Bollen PDJ, Moore C, Kekitiinwa A, et al. The ODYSSEY Trail Team

Published in: Oral Presentation at 10th IAS Conference, July, 21-24th 2019

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14

Apr, 2019

Adult dolutegravir 50mg film-coated tablets in children living with HIV weighing 20 to <25 kg

 

Authors: Bollen P, Turkova A, Mujuru H, et al. for the ODYSSEY Trial Team

Published in: 26th Conference on Retroviruses and Opportunistic Infections, March 4th – 7th, 2019– Seattle. P_830

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26

Dec, 2018

Economic evaluation of weekends-off antiretroviral therapy for young people in 11 countries

 

Authors: Tierrablanca LE, Ochalek J, Ford D, et al; for BREATHER (PENTA 16) Trial Group

Published in: Medicine (Baltimore). 2018;97(5):e9698

Objectives To analyze the cost effectiveness of short-cycle therapy (SCT), where patients take antiretroviral (ARV) drugs 5 consecutive days a week and have 2 days off, as an alternative to continuous ARV therapy for young people infected with human immunodeficiency virus (HIV) and taking efavirenz-based first-line ARV drugs.

Methods We conduct a hierarchical cost-effectiveness analysis based on data on clinical outcomes and resource use from the BREATHER trial. BREATHER is a randomized trial investigating the effectiveness of SCT and continuous therapy in 199 participants aged 8 to 24 years and taking efavirenz-based first-line ARV drugs in 11 countries worldwide. Alongside nationally representative unit costs/prices, these data were used to estimate costs and quality adjusted life years (QALYs). An incremental cost-effectiveness comparison was performed using a multilevel bivariate regression approach for total costs and QALYs. Further analyses explored cost-effectiveness in low- and middle-income countries with access to low-cost generic ARV drugs and high-income countries purchasing branded ARV drugs, respectively.

Results At 48 weeks, SCT offered significant total cost savings over continuous therapy of US dollar (USD) 41 per patient in countries using generic drugs and USD 4346 per patient in countries using branded ARV drugs, while accruing nonsignificant total health benefits of 0.008 and 0.009 QALYs, respectively. Cost-effectiveness estimates were similar across settings with access to generic ARV drugs but showed significant variation among high-income countries where branded ARV drugs are purchased.

Conclusion SCT is a cost-effective treatment alternative to continuous therapy for young people infected with HIV in countries where viral load monitoring is available.

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26

Dec, 2018

Weekends-off efavirenz -based antiretroviral therapy in HIV infected children, adolescents and young adults (BREATHER): extended follow-up results of a randomised, open-label, non-inferiority trial

 

Authors: Turkova A, Moore CL, Butler K, et al. for BREATHER (PENTA 16) Trial Group.

Published in: PLos One. 2018;13(4):e0196239.

Background Weekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation.

Methods BREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virologi- cal suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL?50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz.

Findings Of 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9–216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12–18), median CD4 count 735 cells/μL (IQR 576–968). 16 SCT and 16 CT participants had con- firmed VL?50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50–2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6–10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12;

p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71–8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART fol- lowing viral failure (p = 0.50).

Conclusions Sustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring.

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14

Oct, 2018

Steady-state pharmacokinetics and early safety data in HIV-infected African children weighing 14 to <25kg on film-coated dolutegravir 25mg tablets

 

Authors: Bollen P, Turkova A, Hilda Mujuru H, et al. The ODYSSEY Trial Team

Published in: 10th International Workshop on HIV Pediatrics, Amsterdam, 20-21st July 2018. Poster Number 22

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14

Oct, 2018

ODYSSEY: design, current status, and baseline characteristics

 

Authors: Moore CL,  Kekitinwa A, Kaudha E, et al; the ODYSSEY Trial Team

Published in: 10th International Workshop on HIV Pediatrics, Amsterdam, July 20-21st, 2018. Poster Number 34

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9

Oct, 2018

“I failed to take them as I should and now I’m scared”: how can we support adolescents’ adherence on second line HIV treatment

 

Authors: Bernays S, Namukwaya S, Mupambireyi Z, Nanduudu A, Mujuru H, Turkova A, Gibb DM, Seeley J, and the ODYSSEY Trial Team.

Published in: 10th International Workshop on HIV Pediatrics, Amsterdam, July 20-21st 2018. Poster number 117

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