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Antiretroviral therapy for pregnant women living with HIV or hepatitis B: a systematic review and meta-analysis
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  • Published on:
    Authors respond to "Comments on PROMISE data interpretation in Siemieniuk meta-analysis from PROMISE team"
    • Reed A.C. Siemieniuk, Physician McMaster University
    • Other Contributors:
      • Graham P. Taylor, Physician
      • Gordon H. Guyatt, Physician
      • Lyubov Lytvyn, Patient involvement liaison
      • Yaping Chang, Methodologist
      • Paul E. Alexander, Methodologist
      • Yung Lee, Medical Student
      • Thomas Agoritsas, Physician
      • Arnaud Merglen, Physician
      • Haresh Kirpalani, Physician
      • Susan Bewley, Physician

    Dear Editor:

    We thank Dr. Fowler and colleagues for taking the time to consider and comment on our BMJ Rapid Recommendation (1). They speculate on reasons why tenofovir and emtricitabine increased the risk of neonatal mortality and early preterm delivery in their trial (2) and then say that the current evidence does not support a recommendation for alternative NRTIs over a tenofovir-based antiretroviral therapy (ART) regimen. We do agree that most, but not all, of the evidence comes from a single study, which may have overestimated harm. Our systematic review attempted to generate the current best evidence, and is not definitive: it is moderate-to-low quality for key outcomes (3). However, we disagree with the implication that based on this evidence, most women would choose a tenofovir-based ART regimen.

    The PROMISE authors suggest that results of the comparison between tenofovir-ART and AZT-ART are untrustworthy because the risk of neonatal death was lower in the AZT-ART arm in the earlier period 1 before the tenofovir-ART arm was introduced (2). However, the difference between the two time-periods in the AZT-ART arm could easily be explained by chance (neonatal mortality 1.4% in period 1 vs. 0.6% in period 2, p=0.39; very preterm delivery 3.4% in period 1 vs. 2.6% in period 2, p=0.60). Regardless, the only reliable comparison between tenofovir-ART and AZT-ART is during period 2 when randomisation to both AZT and tenofovir-based ART occurred. Despite these r...

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    Conflict of Interest:
    None declared.
  • Published on:
    Comments on PROMISE data interpretation in Siemieniuk meta-analysis from PROMISE team
    • Mary Glenn Fowler, Pediatric infectious disease and HIV physician Johns Hopkins University School of Medicine, Baltimore, MD
    • Other Contributors:
      • Lynne M Mofenson, Pediatric infectious disease and HIV physician
      • Patricia M Flynn, Pediatric infectious disease and HIV physician
      • Taha E Taha, Pediatric infectious disease and HIV physician

    To the BMJ Editor:

    A recent analysis in BMJ Open accompanied by a clinical practice guideline on antiretroviral therapy (ART) in pregnant women living with HIV by Siemieniuk et al has concluded that “tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine” (1,2). While the clinical practice guideline was based on a systematic review, in reality, the conclusion was based solely on results of the PROMISE study (3). Evidence from large observational studies did not support this recommendation, but was viewed as too low quality to consider in making recommendations. As coauthors of the PROMISE study, we would like to comment on the authors’ conclusion.

    The objective of the PROMISE trial was to compare the efficacy of zidovudine/single-dose nevirapine (AZT-alone) with protease inhibitor-based (lopinavir-ritonavir) combination ART (AZT-based ART [AZT-ART] or tenofovir-based ART [TDF-ART]) to prevent mother-to-child transmission in women with CD4 cell count >350 cells/mm3 (3).The study enrolled during two periods, and the comparisons of the TDF-ART arm to the other arms are restricted to the women who were concomitantly randomized among the three study arms, which occurred only in the second period of the study. In Period 1 – accounting for about two-thirds of enrollment - only hepatitis B virus (HBV)-coinfected women (~1% of overall enrollment) were randomized to TDF-ART vs...

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    Conflict of Interest:
    We are the primary authors of the PROMISE study cited as the evidence for the recommendation in this paper ; we disagree with the final conclusion based on our data.