American Journal of Obstetrics and Gynecology
SupplementUse of single-dose nevirapine for the prevention of mother-to-child transmission of HIV-1: does development of resistance matter?
Section snippets
NVP Resistance in Women After SD-NVP
Antiretroviral resistance is detected most commonly through the use of genotypic assays. Genotyping assays detect viral resistance-associated mutations in the relevant viral genes. Most commonly used genotyping assays can detect drug-resistant viruses that represent at least 10%-20% of the circulating virus population. More sensitive assays can detect specific resistance-associated mutations at lower levels.
NVP resistance frequently emerges after SD-NVP exposure and has been detected in 19%-76%
NVP Resistance in Infants After SD-NVP
NVP resistance is also seen in infants who become HIV-infected, despite SD-NVP prophylaxis. At 6-8 weeks of age, NVP resistance was detected in 46% of infected Ugandan infants17 and 87% of Malawian infants42 and at 4-12 weeks in 45% of South African infants.43 The most common NVP-resistance mutation that has been detected in infants after SD-NVP exposure is tyrosine to cysteine at HIV reverse transcriptase codon 181.17, 25 Routine genotyping assays suggest that most NVP-resistant strains fade
Response to Treatment After SD-NVP
Several studies suggest that NNRTI-containing treatment regimens may still be effective as first-line therapy in women with previous SD-NVP exposure, particularly if, as 1 study suggests, there is sufficient time between SD-NVP dosing and treatment initiation. (Table 1).
The Thai Perinatal HIV Prevention Trials (PHPT)-2 study assessed the efficacy of an NNRTI-based treatment regimen in SD-NVP–exposed vs unexposed women.18 The analysis included 269 women who had previously received short- or
Effectiveness of SD-NVP in Subsequent Pregnancies
Two studies have evaluated the effectiveness of SD-NVP prophylaxis in women who received the same regimen in a previous pregnancy. A follow-up study of 207 women from the HIVNET 012 cohort and a PMTCT program in Uganda found no difference in transmission risk among NVP-exposed women compared with unexposed women (20.6% vs 18.7%, respectively; P = .81). In that study, the median time between delivery and previous SD-NVP exposure was 32 months.52 Similar results were seen in a study that was
Addition of Antiretrovirals After Delivery to Reduce the Risk of NVP Resistance After SD-NVP
Two studies have investigated whether the risk of NVP resistance after SD-NVP can be reduced by the addition of ZDV/3TC for 3-7 days after delivery.54, 55, 56 This “tail” provides additional antiretroviral coverage while NVP levels in plasma are declining. A study from South Africa compared NVP resistance among 226 women who received a short antenatal course of ZDV plus either SD-NVP alone or SD-NVP plus a 4- or 7-day ZDV/3TC tail. The risk of NVP resistance was 60% in women and 78% in infants
Ongoing and Planned Studies
At least 4 ongoing studies are evaluating interventions to complement NVP-containing PMTCT regimens and to reduce the development of NNRTI resistance mutations. These include (1) a US Centers for Disease Control and Prevention–sponsored study of 200 mother-infant pairs in Lilongwe, Malawi, where women and newborn infants receive SD-NVP plus a 7-day tail of ZDV/3TC or SD-NVP alone; (2) a study in Lusaka, Zambia, where 400 women who accessed SD-NVP in addition to ZDV in antenatal care are
Comment
Although preliminary, currently available data indicate that SD-NVP is effective for PMTCT in repeat pregnancies and that SD-NVP exposure does not compromise future treatment with an NNRTI-regimen, so long as treatment is initiated at least 6 months after SD-NVP exposure. The 1 study that assessed virologic response rates among women who initiated treatment within 6 months of SD-NVP exposure found a suboptimal response rate in these women, compared with women who began treatment >6 months after
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The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the US Centers for Disease Control and Prevention.