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Transmission rates in consecutive pregnancies exposed to single-dose nevirapine in Soweto, South Africa and Abidjan, Cote d'Ivoire
Global Health Sciences Literature Digest
Published July 2, 2007
Journal Article

Martinson NA, Ekouevi DK, Dabis F, Morris L, Lupodwana P, Tonwe-Gold B, et al. Transmission rates in consecutive pregnancies exposed to single-dose nevirapine in Soweto, South Africa and Abidjan, Cote d'Ivoire. J Acquir Immune Defic Syndr 2007 Jun 1;45(2):206-9.

Objective

To determine the effectiveness of singe-dose nevirapine (sdNVP) in preventing peripartum maternal-to-child transmission in successive pregnancies.

Study Design

Prospective cohort study of women and infants exposed to sdNVP in two successive pregnancies.

Setting

Soweto, South Africa and Abidjan, Cote d'Ivoire. Recruitment occurred between June 2003 and April 2005 in Soweto, and between March 2001 and July 2003 in Abidjan. At the time of the study, highly active ARV therapy was not widely available for pregnant women at either site.

Participants

Women who had been exposed to sdNVP during two pregnancies were recruited. In Soweto, 120 women attending the PMTCT program a second time were enrolled. The protocol for HIVNET 012 trial was used.(1) Eligibility criteria included written evidence that sdNVP had been dispensed during the previous pregnancy and maternal self-report of taking NVP at the onset of labor and of not breastfeeding the infant. In Abidjan, 41 women who were part of the ANRS Ditrame Plus Study (2) were identified and followed. HIV test results were available for 128 infants (90 in Soweto and 38 in Abidjan) from the first pregnancy and for 145 infants (108 in Soweto and 37 in Abidjan) from the second pregnancy. The median age of women at their initial exposure to sdNVP in Soweto and Abidjan was 26 years (interquartile range [IQR]: 22-29) and 28 years (IQR: 24-31), respectively; median delivery interval was 21 months (IQR: 15-29) and 26 months (IQR: 20-32), respectively.

Interventions

In Soweto, the HIV Network for Prevention Trials (HIVNET) 012 sdNVP regimen was used for the duration of this study.(3) In Abidjan, women received a short peripartum course of zidovudine (ZDV) plus sdNVP, or ZDV plus lamivudine (3TC) with sdNVP. Neonates received ZDV syrup (2 mg/kg every 6hours) for seven days and sdNVP (2 mg/kg) three days after birth.

Primary Outcomes

In Soweto, HIV status of the infant was assessed using the Amplicor HIV-1 qualitative assay, version 1.5. The HIV status of the previous child was ascertained in the same manner if the child was <18 months of age or by HIV EIA if the child was ≥18 months old. In Abidjan, pediatric HIV status was assessed using a validated real-time HIV RNA PCR on plasma samples at four weeks and confirmed at six weeks if positive.

Results

In Soweto, MTCT of live-born infants during the first pregnancy was 11.1% (95% CI:5.5% to 19.5%) and 11.1% (95% CI:5.9- 18.6%) in the second pregnancy. In Abidjan, the transmission rate of live-born infants was 13.2% (95% CI: 4.4- 28.1%) in the first pregnancy and 5.4% (95% CI:0.6- 18.2%) in the second pregnancy. Differences between first and second pregnancy MTCT were not statistically different (unpaired analysis). When stillbirths and infant deaths were also included, transmission rates in Soweto were 22.7% (23/101), 95% CI:15.0 - 32.2%) for the first pregnancy and 10.7% (11/103, 95% CI:5.4- 18.3%) for the second; in Abidjan, transmission rates were 19.5% (8/41) (95% CI:8.8- 34.9%) in the first pregnancy and 14.6% (6/41)(95% CI:5.6- 29.2%) in the second. These differences were not statistically significant.

Conclusions

The authors conclude that vertical peripartum transmission rates did not increase at either study site, despite presumed progression of maternal HIV disease between deliveries or the possibility of resistance mutations selected by initial use of sdNVP.

Quality Rating

Based on the Newcastle-Ottawa quality assessment scale, this study was of adequate quality. The study was limited by the small sample size and by differences in sdNVP-containing PMTCT regimens between the two sites. This study did not provide information on HIV disease progression among mothers, actual breastfeeding practices, or mode and duration of delivery. In addition, resistance testing was not performed.

In Context

The impact of prior exposure to sdNVP on MTCT transmission in subsequent pregnancies is an important issue because maternal resistance is detectable shortly after delivery and persists months after exposure. (3) Many countries with high HIV prevalence have total fertility rates in excess of four births per woman, and, therefore, repeated use of NVP will occur. An unpublished report from Kampala, Uganda comparing transmission rates between sdNVP-naive and sdNVP-exposed women showed that transmission after a second exposure was not significantly higher.(4) The current study does not report resistance data, but the authors postulate that the time elapsed between first labor and second exposure to sdNVP may have allowed NVP-resistant populations to wane. In this study, higher transmission rates were found in women whose interdelivery time was <12 months, compared with those with times of ≥12 months. Findings from another study showed that fewer women failed ARV therapy if they were initiated at least six months after their exposure to sdNVP (5)

Programmatic Implications

The results of this study suggest that nevirapine continues to be effective in prevention of MTCT when used in two consecutive pregnancies, although the addition of a short postpartum course of AZT plus 3TC added to sdNVP has been shown to reduce selection of maternal and infant non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance markedly. However, more research is needed to elucidate the effectiveness of sdNVP-containing MTCT regimens under a variety of conditions, particularly in settings where sdNVP is the mainstay of programs. In addition, increased length of time between deliveries of subsequent infants may also reduce transmission facilitated by the development of resistance.

References

  1. Flys T, Nissley DV, Claasen CW, Jones D, Shi C, Guay LA, et al. Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis 2005 Jul 1;192(1):24-9.
  2. Dabis F, Bequet L, Ekouevi DK, Viho I, Rouet F, Horo A, et al. Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission. AIDS 2005 Feb 18;19(3):309-18.
  3. Flys T, Nissley DV, Claasen CW, Jones D, Shi C, Guay LA, et al. Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012. J Infect Dis 2005 Jul 1;192(1):24-9.
  4. Eure C, Bakaki P, McConnell, et al. Effectiveness of repeat single-dose nevirapine in subsequent pregnancies among Ugandan women [abstract 125]. Presented at: 13th Conference on Retroviruses and Opportunistic Infections; 2006; Denver. (No abstract available.)
  5. Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, et al. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 2007 Jan 11;356(2):135-47.