Background
Nevirapine (NVP) has been demonstrated to be very effective in the prevention of mother-to-child transmission (PMTCT) of HIV. However, several studies have shown a high rate of mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in women (as well as infants) given single-dose NVP in PMTCT protocols.
Exposure to Intrapartum Single-dose Nevirapine and Subsequent Maternal 6-Month Response to NNRTI-based Regimens
Abstract: Jourdain G, Ngo-Giang-Huong N, Tungyai P, et al. Exposure to Intrapartum Single-dose Nevirapine and Subsequent Maternal 6-Month Response to NNRTI-based Regimens. 11th CROI, Abstract 41LB.
Description: This study examined the effect of intrapartum NVP exposure on subsequent antiretroviral therapy (ART). Subjects included 255 women who had received third-trimester zidovudine prophylaxis plus single-dose intrapartum nevirapine (NVP) (n=213), or zidovudine alone (n=42), as part of a PMTCT study and who subsequently started NNRTI-based ART. Three study groups were defined: those without prior NVP exposure, those with NVP exposure but no NNRTI mutations on postpartum genotype, and those with NVP exposure and NNRTI mutations.
Results: A pharmacokinetic study on a random sample of NVP-exposed women showed detectable NVP levels up to 19 days postpartum. At 12 days postpartum, 18% of the NVP-exposed women had at least one NNRTI mutation on genotype.
At six months after initiation of ART (primarily NVP + lamivudine + stavudine), significant differences in virologic suppression (defined as HIV viral load of either <400 or <50 RNA copies per mL of plasma) were seen among the groups:
| Level of viral suppression(HIV RNA copies /mL) | No NVP exposure | NVP exposure, no NNRTI mutations | NVP exposure, NNRTI mutations |
| <400 | 86% | 80% | 68% |
| <50 | 75% | 53%* | 34%* |
*p <0.001 for trend
CD4 increases were similar in the three groups.
For women who initiated ART more than six months after delivery, viral suppression to <400 copies/mL occurred more frequently than in those who started ART earlier; no significant difference based on timing of ART was seen when suppression to <50 copies/mL was examined.
Comment: In mothers who had received a single dose of NVP, subsequent ART resulted in decreased rates of virologic suppression to <50 copies/mL at six months, even in those who had no detectable NNRTI mutations in the immediate postpartum period.
HIV infection dramatically reduces infant survival, and NVP is currently the most effective and accessible PMTCT intervention in many resource-poor settings. This study shows that NVP used for PMTCT can compromise subsequent treatment of the mother with an NNRTI-containing regimen. . Intervention strategies that both reduce vertical transmission and protect treatment options for women and children are needed. Ideally, fully suppressive ART would be available to all expectant mothers with HIV. Where NVP remains the best available option for PMTCT, ART regimens that will not be compromised by NNRTI resistance (eg, 2 nucleoside analogues + a protease inhibitor) should be considered for women requiring ART who have previously received single-dose NVP.
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