Single-dose nevirapine

Results from two very large clinical trials involving African women demonstrated that one or two doses of nevirapine (NVP) during and after labour can reduce the rate of HIV transmission significantly .

As women in resource-limited settings do not always have access to antenatal care, many are not tested for HIV until they come to the clinic in labour. Treatment during labour and after childbirth can still reduce MTCT.

In the HIVNET 012 study, 626 women took a single dose of 200mg nevirapine at the onset of labour and a dose of 2mg/kg was given to the baby three days after birth. Compared with an AZT regimen involving treatment of the mother during labour and the infant during the first week of life, the NVP-treated group had a 47% reduction in the risk of transmission.1 

Further follow-up from HIVNET 012 suggested that the reduction in the risk of transmission associated with NVP prophylaxis persists for at least the first year of life, despite the ongoing risk posed by breastfeeding. Furthermore, NVP was more effective in reducing transmission than AZT in women with CD4 counts below 200 cells/mm3 . 2

These findings were corroborated by the South African SAINT study, which showed that giving the mother a dose of NVP during labour and to both mother and infant after delivery was as effective in reducing the rate of perinatal transmission as a seven-day course of AZT and 3TC.3 

However, a high rate of nevirapine resistance was detected among mothers and infants when the mother took two doses of nevirapine. Because of these concerns, future studies gave only one dose of NVP to the mother at the onset of labour and one dose to the infant within 72 hours of birth.

This cheap and effective way of reducing vertical transmission made possible the widespread implementation of programmes to prevent mother-to-child transmission of HIV in the most resource-limited countries. Nevirapine can be given to pregnant women with HIV, with instructions to take one dose for themselves when they go into labour and then to give one dose of nevirapine syrup to their child. This approach was shown to be effective in a study from Uganda, reducing transmission by approximately 60% when compared to historic levels.4

Other studies have examined the effect of combining short course AZT with single-dose nevirapine (SD-NVP). A large randomised, double-blind, placebo-controlled Thai study called Perinatal HIV Prevention Trial-2 (PHPT-2) looked at the efficacy of the standard Thai AZT prophylactic regimen (300mg bid starting at week 28 of gestation) to mother and child with the addition of NVP to the mother's therapy versus NVP added to both the mother's and the child's regimen.

After the first interim analysis, the AZT-only arm was discontinued, as transmission was significantly higher (MTCT rate was 7%). Transmission rates were 2% in the arm that gave SD-NVP to mother and child as compared to 3% when infants were only given placebo.5 

Single-dose nevirapine given only to the infant has been shown to lead to fewer transmissions than six weeks of AZT. This may therefore be a useful strategy in situations where the mother does not access antenatal care or HIV testing. Risk factors for transmission were lower CD4 cell count and higher viral load in the mother and breastfeeding.6

The study investigators found that as long as the mother was given NVP within 48 hours of delivery and the infants within 72 hours of birth, the timing of NVP administration did not affect PMTCT rates.7

References

  1. Guay LA et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 354: 795-802, 1999
  2. Jackson JB et al. A phase I/II study of nevirapine for pre-exposure prophylaxis of HIV-1 in uninfected subjects at high risk. AIDS 17: 547-553, 2003
  3. Moodley D et al. Evaulation of safety and efficacy of two simple regimens for the prevention of mother to child transmission (MTCT) in HIV infection: nevirapine vs lamivudine and zidovudine used in a randomised clinical trial (the SAINT study). 13th International AIDS Conference, Durban, abstract TuOrB356, 2000
  4. Kagaayi J et al. Maternal self-medication and provision to newborns by women in Rakai, Uganda. J Acquir Immune Defic Syndr 39: 121-124, 2005
  5. Lallemant M et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 351: 217-228, 2004
  6. Gray GE et al. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers. AIDS 19: 1289-1297, 2005a
  7. Chi BH et al. Timing of maternal and neonatal dosing of nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024. AIDS 19: 1857-1864, 2005