Efficacy and Safety of Dolutegravir or Darunavir in Combination with Lamivudine plus either Zidovudine or Tenofovir for second-line Treatment of HIV Infection (NADIA): week 96 results from a Prospective, Multicentre, Open-label, Factorial, Randomised, Non-inferiority trial

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dc.contributor.authorPaton, Nicholas I.
dc.contributor.authorMusaazi, Joseph
dc.contributor.authorKityo, Cissy
dc.contributor.authorWalimbwa, Stephen
dc.contributor.authorHoppe, Anne
dc.contributor.authorBalyegisawa, Apolo
dc.contributor.authorMirembe, Grace
dc.contributor.authorLugemwa, Abbas
dc.contributor.authorAtegeka, Gilbert
dc.contributor.authorMugerwa, Henry
dc.contributor.authorKambugu, Andrew
dc.date.accessioned2023-09-25T18:26:00Z
dc.date.available2023-09-25T18:26:00Z
dc.date.issued2022
dc.description.abstractWHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine. In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.en_US
dc.identifier.citationPaton, N. I., Musaazi, J., Kityo, C., Walimbwa, S., Hoppe, A., Balyegisawa, A., ... & Walker, S. (2022). Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. The Lancet HIV, 9(6), e381-e393.https://doi.org/10.1016/en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/9264
dc.language.isoenen_US
dc.publisherThe Lancet HIVen_US
dc.subjectHIVen_US
dc.subjectTenofoviren_US
dc.subjectDolutegraviren_US
dc.titleEfficacy and Safety of Dolutegravir or Darunavir in Combination with Lamivudine plus either Zidovudine or Tenofovir for second-line Treatment of HIV Infection (NADIA): week 96 results from a Prospective, Multicentre, Open-label, Factorial, Randomised, Non-inferiority trialen_US
dc.typeArticleen_US
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Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial
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