Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the prevention of mother-to-child HIV transmission: a randomized clinical trial

James A McIntyre, Mark Hopley, Daya Moodley, Marie Eklund, Glenda E Gray, David B Hall, Patrick Robinson, Douglas Mayers, Neil A Martinson, James A McIntyre, Mark Hopley, Daya Moodley, Marie Eklund, Glenda E Gray, David B Hall, Patrick Robinson, Douglas Mayers, Neil A Martinson

Abstract

Background: Single-dose nevirapine (sdNVP)-which prevents mother-to-child transmission of HIV-selects non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance mutations in the majority of women and HIV-infected infants receiving it. This open-label, randomised trial examined the efficacy of short-course zidovudine (AZT) and lamivudine (3TC) with sdNVP in reducing NNRTI resistance in mothers, and as a secondary objective, in infants, in a setting where sdNVP was standard-of-care.

Methods and findings: sdNVP alone, administered at the onset of labour and to the infant, was compared to sdNVP with AZT plus 3TC, given as combivir (CBV) for 4 (NVP/CBV4) or 7 (NVP/CBV7) days, initiated simultaneously with sdNVP in labour; their newborns received the same regimens. Women were randomised 1ratio1ratio1. HIV-1 resistance was assessed by population sequencing at: baseline, 2, and 6 wk after birth. An unplanned interim analysis resulted in early stopping of the sdNVP arm. 406 pregnant women were randomised and took study medication (sdNVP 74, NVP/CBV4 164, and NVP/CBV7 168). HIV-1 resistance mutations emerged in 59.2%, 11.7%, and 7.3% of women in the sdNVP, NVP/CBV4, and NVP/CBV7 arms by 6 wk postpartum; differences between NVP-only and both NVP/CBV arms were significant (p<0.0001), but the difference between NVP/CBV4 and NVP/CBV7 was not (p = 0.27). Estimated efficacy comparing combined CBV arms with sdNVP was 85.6%. Similar resistance reductions were seen in infants who were HIV-infected by their 6-wk visit.

Conclusions: A short course of AZT plus 3TC, supplementing maternal and infant sdNVP, reduces emergent NNRTI resistance mutations in both mothers and their infants. However, this trial was not powered to detect small differences between the CBV arms.

Trial registration: www.ClinicalTrials.govNCT 00144183.

Trial registration: ClinicalTrials.gov NCT00144183.

Conflict of interest statement

M. Hopley, M. Ekelund, D. B. Hall, and P. Robinson are employed by Boehringer Ingelheim, the sponsor of the study, and D. Mayers was employed by Boehringer Ingelheim at the time of the study. Employees of the sponsor were involved in protocol design, were responsible for data management and statistical analyses, and assisted with the preparation of the paper. J. A. McIntyre and G. E. Gray have received research funding, travel grants and speaker's honoraria from Boehringer Ingelheim and Glaxo SmithKline. N. A. Martinson and D. Moodley declare no competing interests.

Figures

Figure 1. CONSORT diagram of the trial.
Figure 1. CONSORT diagram of the trial.
Screening was while women were pregnant and randomisation was during labour (CBV, 3TC with AZT).

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