CROI: Two studies show single-dose nevirapine prevents HIV transmission in consecutive pregnancies

Women who have used single-dose nevirapine (Viramune) to prevent mother to child transmission (PMTCT) of HIV can use it with equal or greater success during a second delivery, according to studies presented at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver last week.

A study conducted in Uganda, given as an oral presentation by Dr Paul Bakaki, on behalf of the Makerere University, Kampala, Uganda and Johns Hopkins University Research Collaboration, (downloadable as an mp3 file here demonstrated that sdNVP is as effective in the second pregnancy as the first. Supporting evidence was provided by a second study, by Martinson et al, in women from South Africa and the Côte d’Ivoire — where different HIV subtypes are prevalent — suggesting the results should be generalisable throughout Africa. The second study also found that women who previously transmitted HIV to their infants despite single-dose nevirapine, do not necessarily transmit to their subsequent infant.

Single-dose nevirapine background

The benchmark study, HIVNET 012, which was conducted in Uganda, demonstrated that single-dose nevirapine administered at the onset of labour to HIV-infected mothers and to newborn infants significantly reduces the risk of mother-to-child transmission. The treatment has since become widely used for prevention of mother-to child transmission programmes in resource-limited settings. "More than half a million women have received single-dose nevirapine already and it is likely that more women will be returning a second time," wrote Martinson et al.

However, after nevirapine-resistance conferring mutations were detected in some women exposed to single-dose nevirapine, there were concerns that the drug might not work as well in subsequent pregnancies.

Soweto/Abidjan

Consistent results were observed in a study that evaluated the effectiveness of single-dose nevirapine in consecutive pregnancies in Soweto, South Africa and Abidjan, Côte d’Ivoire. Preliminary results from the South African patients in this study were presented at last year’s conference.

A total of 76 HIV-infected women were identified in Soweto who had received single-dose nevirapine in a previous pregnancy, delivered live infants on both occasions, did not breastfeed their first infant, and both infants were tested for HIV. A similar group of 35 women were identified in Abidjan and included in the analysis.

The median age of women at their initial exposure to single-dose nevirapine was similar, 26-27 year-old, in both settings, as was the time: 22-23 months between pregnancies.

Out a total of 112 births, HIV was transmitted to twelve infants in both the first and second pregnancies — however, the mothers who transmitted to their infants in the first pregnancy did not transmit the virus in the second pregnancy.

The Ugandan study

The current Ugandan study compared infection rates after single-dose nevirapine among infants born to women with prior nevirapine exposure (cases) to the rates among infants of nevirapine-naïve pregnant women (controls) — some of whom chose to nourish their infants with breastmilk or mixed feeding (which carries a higher risk of transmission). The study combined data from a retrospectively studied group, from women involved in the HIVNET 012 study for whom data on subsequent pregnancies were available, as well as from women prospectively studied (in whom baseline variables such as viral load and CD4 cell data could be assessed).

In the prospectively studied group, there were no significant differences in baseline maternal viral load, CD4 cell count or age group between cases and controls. The time between deliveries was around twelve months.

Final infection status data were available at six months for about one hundred infants in both the prospective and retrospective cohorts, for a combined total of 201 infants.

In the first pregnancy, the infection rate ranged between 17-18% for the retrospective and prospective groups. In the second pregnancy, the infection rate was around 12% in the retrospective group and 17% in the prospective group. In both groups and overall, there were no significant differences in infant infection rates for nevirapine-experienced compared to nevirapine-naive women.

Conclusion

"It appears that the effectiveness of single-dose nevirapine alone or in combination is not reduced by previous exposure. This may be due to reversion to wild type virus in the absence of a sustained selection pressure," wrote Martinson et al. They suggested that changes in guidelines for the use of single-dose nevirapine alone or in combination in women attending the prevention of mother-to-child transmission program a second time are not necessary.

Dr Bakaki agreed. "The results are reassuring and provide evidence that use of single-dose nevirapine in subsequent pregnancies remains an effective option for PMTCT in resource-limited settings where more complex regimens are not yet feasible," he concluded.

However, while these results are encouraging, it must be remembered that another downside to the development of resistance after exposure to single-dose nevirapine is that it may limit the mother’s response to subsequent treatment with a nevirapine-containing ART regimen for her own health. For women identified as HIV-positive in PMTCT programmes, a more complete option than single-dose nevirapine should be available by her second pregnancy, most experts now agree.