Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

Effect of Adherence to Primaquine on the Risk of Plasmodium Vivax Recurrence: A Systematic Review and Individual Patient Data Meta-Analysis (#310)

Parinaz Mehdipour 1 , Robert J Commons 2 3 , Ric N Price 2 3 4 , Saber Dini 1 , Julie A Simpson 1
  1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
  2. Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
  3. WorldWide Antimalarial Resistance Network (WWARN), Oxford, United Kingdom
  4. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

Introduction: Adherence is a major barrier to the effectiveness of primaquine radical cure regimens. This study investigates the effect of reduced adherence on the risk of P. vivax recurrence.

Methods: Efficacy studies of uncomplicated P. vivax including a treatment arm with daily primaquine and published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardised methodology. Adherence to primaquine was assessed based on supervision status and the total versus expected mg/kg dose administered. The effect of adherence to primaquine on the incidence risk of P. vivax recurrence between days 7 and 90 after starting treatment was investigated by Cox regression analysis.

Results: Of 82 eligible studies, 32 were available including 6,917 patients from 18 countries. For supervision of primaquine, 2,790 patients (40.3%) had poor adherence (<50%) and 4,127 (59.6%) had complete adherence (90%). Among 3,706 patients with information on total mg/kg dose received, 347 (9.4%) had poor adherence (<50%), 88 (2.4%) had moderate adherence between 50-90%, and 3,271 (88.2%) had complete adherence to treatment (90%). The risk of recurrence by day 90 was 15.5% [95% Confidence Interval: 13.4-17.9] in patients with poor adherence compared to full adherence 7.9% [95% CI: 6.4-9.8] by supervision. The corresponding risk for adherence by total dose was 30% [7.0-82.5] in patients with poor adherence and 23.7% [13.5-47.7] in patients with moderate adherence compared with 7.1% [5.6-9.0] in patients with full adherence. After controlling for confounders, the rate of the first recurrence was increased following poor versus full adherence by supervision (Adjusted Hazard Ratio (AHR)=2.5 [95% Confidence Interval: 2.0-3.5]). The corresponding rate was also increased in poor (AHR=5.9 [3.2-10.6]) and moderate adherence (AHR=5.4 [2.8-10.5]) groups compared to the complete adherence by total dose.

 Conclusion: Reduced adherence, including less supervision, increases the risk of vivax recurrence.