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Antiretroviral Drugs to Treat HIV Infection. Credit NIAID

ACT-ARV Safety Study Group

This is an extension of a planned dihydroartemisinin-piperaquine (DP) Safety Study Group, which aims to consider the effect of HIV disease and co-administration of widely-used antiretroviral (ARVs) on the safety of DP. Due to a lack of available DP studies, the individual patient data (IPD) meta-analysis will have greater public health value when these results were compared to other ACTs.

Timeline

The search is currently being updated and a draft publication will be circulated to study group members in due course with submission expected in Q1 or 2 2019

Rationale

Data on the safety of concomitant ACT-ARV use is scarce [1, 2], and a lack of systematically collected, standardised safety data in this population limits the ability to use this data to inform optimal drug selection and dosing in this group of vulnerable patients. Combining safety data is particularly challenging due to heterogeneity in how studies are conducted. Therefore, beyond an IPD meta-analysis analysis to compare adverse events (AEs) in patients with HIV (with or without ARVs) taking DP compared to other antimalarials, we will also aim to understand the complexities of integrating individual level safety analyses into WWARN’s global data platform. This is expected to enhance abilities to link efficacy and safety data for dose optimisation applicable across a range of drugs.

Objective

  • To define the effect of HIV disease and/or co-administration of widely-used ARVs on DP safety (AEs) and compare this to other ACTs

Inclusion criteria for data sets

  • Clinical studies in patients with OR people at risk of falciparum malaria (either alone or mixed infections) OR healthy volunteers
  • At least one ACT dose given, whether used for uncomplicated malaria treatment OR chemoprevention OR in healthy volunteers
  • HIV infected AND / OR treated with ARVs
  • Individual AE data available

Data standardisation and analysis

After upload to the WWARN Data Repository, data sets will be transformed, standardised and combined according to WWARN Data Management and Statistical Analysis Plans. The statistician appointed to the project will develop a statistical analysis plan specifically for the meta-analysis, in collaboration with Study Group members

The pooled databases will aim to include the following, if available:

  • Demographics
  • Baseline patient characteristics
  • Clinical signs and symptoms over time
  • Date ARV started and current regimen
  • CD4 and viral load in HIV infected patients, if available
  • Dosing (mg/kg dose and dosing times) for antimalarials and ARVs
  • Medical history
  • Adverse events
  • Concomitant medications (including traditional, alternative and complementary medicines)

Study group governance and membership

The Study Group comprises participating investigators who contribute relevant data sets to the pooled analysis. Data sets remain the property of the investigator. The Study Group will be asked to assist in the identification of any further relevant studies and will collectively make decisions with respect to data analysis plans and plans for publication, in line with the WWARN Publication Policy. The Study Group will be led by Dr Elizabeth Allen, Scientific Coordinator WWARN Pharmacology Group, at the University of Cape Town

For further information, email Elizabeth Allen (Elizabeth [dot] allen [at] wwarn [dot] org) or Karen Barnes (karen [dot] barnes [at] wwarn [dot] org)

References

1. Kamya MR, Yeka A, Bukirwa H, Lugemwa M, Rwakimari JB, Staedke SG, Talisuna AO, Greenhouse B, Nosten F, Rosenthal PJ, et al: Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial. PLOS Clin Trial 2007, 2:e20.

2. Katrak S, Gasasira A, Arinaitwe E, Kakuru A, Wanzira H, Bigira V, Sandison TG, Homsy J, Tappero JW, Kamya MR, Dorsey G: Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children. Malar J 2009, 8:272