Abstract
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. 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. 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. www.ClinicalTrials.govNCT 00144183.
Highlights
Single-dose nevirapine given to human immunodeficiency virus (HIV)-1 infected women in labour, followed by a single dose administered to their infants within 72 h of birth, is the simplest regimen to prevent intrapartum mother-to-child transmission (MTCT) of HIV-1 [1,2,3] and is used extensively in resource-limited settings
In October 2008, the US National Institutes of Health (NIH) released a press statement reporting that a randomised trial comparing the efficacy of NVP-based highly active antiretroviral therapy (HAART) to ritonavir-boosted-lopinavir HAART in women previously exposed to Single-dose nevirapine (sdNVP) was terminated early because of higher rates of virological failure and death in the NVP-based HAART arm; this finding was accentuated in women with NVPresistant HIV
The primary objective of this trial—the Treatment Options Preservation Study (TOPS)—was to compare the selection of maternal nucleoside reverse-transcriptase inhibitor (NNRTI) resistance mutations after receipt of three NVP-containing regimens for prevention of mother-tochild transmission (PMTCT): sdNVP alone or sdNVP combined with short courses of AZT and lamivudine (3TC), given as combivir, initiated simultaneously with the dose of NVP at the onset of labour to mother and continued postpartum
Summary
Single-dose nevirapine (sdNVP) given to HIV-1 infected women in labour, followed by a single dose administered to their infants within 72 h of birth, is the simplest regimen to prevent intrapartum mother-to-child transmission (MTCT) of HIV-1 [1,2,3] and is used extensively in resource-limited settings. The primary objective of this trial—the Treatment Options Preservation Study (TOPS)—was to compare the selection of maternal NNRTI resistance mutations after receipt of three NVP-containing regimens for prevention of mother-tochild transmission (PMTCT): sdNVP alone or sdNVP combined with short courses (either 4 or 7 d) of AZT and lamivudine (3TC), given as combivir, initiated simultaneously with the dose of NVP at the onset of labour to mother and continued postpartum. 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-ofcare. MTCT is preventable and there is a global commitment, agreed at the UN General Assembly Session on HIV/AIDS in 2001, to reduce the proportion of infants infected with HIV by 50% by 2010
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