Single dose nevirapine infant prophylaxis to reduce mother to child transmission may have similar efficacy to maternal and infant doses

13 October 2005. Related: Pregnancy.

Polly Clayden, HIV I-Base

Administration of single-dose nevirapine for mother to child transmission prophylaxis is associated with rapid emergence of nevirapine resistance in both the mother and HIV-infected infants.

This is likely to increase risk of treatment failure in women who subsequently receive nevirapine-containing HAART, which despite limited coverage is an important consideration as treatment programmes roll out. Single-dose nevirapine prophylaxis given only to the infant would avoid the risk of nevirapine resistance in the mothers.

A study conducted by Glenda Gray and co-workers published in the August 12 edition of AIDS compared HIV infection rates at 12 weeks in a group of infants born to HIV positive mothers, uninfected at birth and randomised to receive either single dose nevirapine (10 mg/ml oral suspension at a dose of 2 mg/kg) or 6 weeks AZT (10 mg/ml at a dose of 4 mg/kg every 12 hours) [1]. The effect of breastfeeding on the efficacy of the regimens was a secondary objective of the study.

Women delivering with unknown HIV status at three South African clinics were offered voluntary counselling and rapid testing. Women testing HIV positive were offered enrolment into the trial.

Pre term infants were excluded from the study if they weighed < 1200g, needed ventilation, were unable to take oral medication or had congenital abnormalities. Informed consent and randomisation took place within 24 hours of delivery. Formula was provided for women who opted not to breastfeed and those opting to breastfeed were advised to do so exclusively.

From October 2000 to September 2002 1051 infants were randomised into the study: 533 in the AZT arm and 518 in the nevirapine arm. At 12 weeks, 718 infants had evaluable results.

Overall 12-week mother to child transmission probability was 16.3% (95%, CI: 13.4-19.2%). Among infants not infected at birth, 24 (7.9%) new infections were in the nevirapine arm and 41(13.1%) in the AZT arm (p=0.06).

There was no statistical significance in the incidence of serious adverse events between the two arms.

The additional infection rate in the breastfed infants in the AZT arm was 20.6% compared with 11.1% in those infants who were not breastfed (p=0.004). The additional infection rate in the breastfed infants in the nevirapine arm was 9.9% compared with 7.3% (p=0.3) in the non-breastfed arm.

The authors report that in multivariate analysis, maternal viral load, CD4 count, breastfeeding and infant AZT were independently associated with an increased risk of infection between day 10 and day 100. Maternal CD4 count < 500 cells/mm3 was associated with a twofold increase in transmission (multivariate OR, 2.5; 95% CI, 1.3-5.0); a maternal viral load of > 50 000 copies/mL led to a more than threefold increased risk of infection (multivariate OR, 3.6; 95% CI, 2.0-6.2). Breastfeeding (multivariate OR, 2.2; 95% CI, 1.3-3.8) was also a significant risk for transmission at week 12.

They found that compared with 6 weeks of AZT, “single-dose nevirapine is easier to implement, is likely to be more cost-effective and adherence would be easier to ensure.” Additionally, in multivariate analysis, the AZT regimen did not appear to be as effective as single-dose NVP in reducing postnatal transmission.

They reported a comparable transmission rate seen in the single-dose single dose arm at 6 weeks (11.9%; 95% CI, 8.8-15.0) to the transmission rate seen in HIVNET 012 (11.8%; 95% CI, 8.2-15.5), where both mother and infant received nevirapine [2]. It was also comparable to the transmission rate at 6-8 weeks (15.3%) seen in infants who received single-dose nevirapine in addition to one week AZT in the Malawi study [3]. Additionally at 12 weeks, the transmission rate seen in the single-dose nevirapine arm (14.3%) was similar to the transmission rate (13.1%) seen in HIVNET 012 at 14-16 weeks.

They note that a limitation of this study is that 20% of infants were lost to follow-up, although the baseline characteristics of the lost to follow up group were similar to those of the infants overall. The authors suggest: “In countries with a high HIV burden, universal nevirapine therapy to all newborns could be considered, particularly where HIV testing and counselling is not available. This could be viewed as analogous to the universal use of tetracycline eye ointment in newborns for preventing ophthalmia neonatorum.”

They conclude: “As access to antiretroviral therapy becomes a reality in countries heavily affected by HIV, attempts should be made to preserve the efficacy of nevirapine for the treatment and care of women. Post exposure prophylaxis to infants provides a valuable alternative.”

References:

1. Gray G, Urban M, Chersich M et al. A randomised trial of two post exposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers. AIDS: Volume 19(12) 12 August 2005 p 1289-1297.
2. Guay L, Musoke P, Fleming T 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 1999; 354:795-802.
3. Taha TE, Kumwenda NI, Gibbons A et al. Short post exposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial. Lancet 2003; 362:1171-1177.