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Use of single-dose nevirapine for the prevention of mother-to-child transmission of HIV-1: does development of resistance matter?

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Nevirapine resistance has been detected in a considerable proportion of women after single-dose nevirapine (SD-NVP) for the prevention of mother-to-child human immunodeficiency virus–1 transmission. As a result, concern has been raised about the effectiveness of subsequent nevirapine-based treatment. Studies in Thailand, Botswana, and South Africa have assessed virologic treatment response after SD-NVP. These studies did not find any significant difference in virologic response for women who began treatment >6 months after SD-NVP exposure. Two studies found worse response rates in women when treatment was initiated within 6 months of SD-NVP exposure. Furthermore, 2 studies found no difference in human immunodeficiency virus transmission rates from mother to child after the receipt of SD-NVP in repeat pregnancies. These data support the use of SD-NVP as 1 option for the prevention of mother-to-child human immunodeficiency virus–1 transmission in resource-limited settings, particularly in settings where more complex regimens are not yet available. Further research in the optimization of perinatal prevention regimens is needed.

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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

References (68)

  • M. Lallemant et al.

    Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand

    N Engl J Med

    (2004)
  • V. Leroy et al.

    Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa?

    AIDS

    (2005)
  • Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial

    Lancet

    (2002)
  • K.M. De Cock et al.

    Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice

    JAMA

    (2000)
  • World Health Organization. Antiretroviral drugs and the prevention of mother-to-child transmission of HIV infection in...
  • World Health Organization. Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants in...
  • S.H. Eshleman et al.

    Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012)

    AIDS

    (2001)
  • S. Palmer et al.

    Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

    Proc Natl Acad Sci U S A

    (2006)
  • G. Jourdain et al.

    Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy

    N Engl J Med

    (2004)
  • A. Chalermchokcharoenkit et al.

    Combination short-course zidovudine plus 2-dose nevirapine for prevention of mother-to-child transmission: safety, tolerance, transmission, and resistance results

  • C.K. Cunningham et al.

    Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316

    J Infect Dis

    (2002)
  • M.G. Fowler et al.

    The interface of perinatal HIV prevention, antiretroviral drug resistance, and antiretroviral treatment: what do we really know?

    J Acquir Immune Defic Syndr

    (2003)
  • World Health Organization. What’s new in the revised ART guidelines for adults and adolescents. Last accessed: May 2,...
  • S.H. Eshleman et al.

    Nevirapine (NVP) resistance in women with HIV-1 subtype C, compared with subtypes A and D, after the administration of single-dose NVP

    J Infect Dis

    (2005)
  • M. Gordon et al.

    Surveillance of resistance in KZN South Africa, including mother-infant pairs 6 weeks after single-dose NVP

    Antivir Ther

    (2004)
  • R. Kantor et al.

    Rapid flux in non-nucleoside reverse transcriptase inhibitor resistance mutations among subtype C HIV-1-infected women after single dose nevirapine

    Antivir Ther

    (2003)
  • D.V. Havlir et al.

    Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients

    J Virol

    (1996)
  • Church JD, Hudelson SE, Guay LA, et al. HIV-1 variants with nevirapine resistance mutations are rarely detected in...
  • T.R. Cressey et al.

    Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1

    J Acquir Immune Defic Syndr

    (2005)
  • E. Muro et al.

    Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine: implications for intervention studies

    J Acquir Immune Defic Syndr

    (2005)
  • P. Musoke et al.

    A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)

    AIDS

    (1999)
  • S.H. Eshleman et al.

    Impact of human immunodeficiency virus type 1 (HIV-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent HIV-1 vertical transmission (HIV network for prevention trials 012 study)

    J Infect Dis

    (2001)
  • M.L. Chaix et al.

    Persistence of nevirapine-resistant virus and pharmacokinetic analysis in women who received intrapartum NVP associated to a short course of zidovudine (ZDV) to prevent perinatal HIV-1 transmission: the Ditrame Plus ANRS 1201/12 Study, Abidjan, Cote d’Ivoire

    Antivir Ther

    (2004)
  • J.B. Jackson et al.

    Identification of the K103N resistance mutation in Ugandan women receiving nevirapine to prevent HIV-1 vertical transmission

    AIDS

    (2000)
  • 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.

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