The effect of repeated single-dose nevirapine for PMTCT in a second pregnancy
Polly Clayden, HIV i-Base
For many people, the most important data from last years CROI for HIV-positive pregnant women globally, were those presented by Neil Martinson from Soweto, looking at HIV transmission in second pregnancies when single dose nevirapine was administered in both pregnancies .
Despite the lack of statistical significance between transmission rates of 132 nevirapine-naive and 75 nevirapine-exposed women (p= 0.096), the finding that the transmission rate rose from 3.8% in the first pregnancy to 10.7% in the second showed a strong trend (RR = 2.3) and provoked much discussion.
In an oral presentation at CROI this year, Paul Bakaki from Uganda presented findings from his group working at Makerre and John Hopkins Universities that addressed the same research question . This study compared women in a retrospective group, who had either received single dose nevirapine or short course AZT in the HIVNET 012 study, followed by single dose nevirapine in a subsequent pregnancy. It also included a prospective group of women from the mother to child transmission (MTCT) programme at Mulago Hospital who were either nevirapine-naive or exposed, and who then received single dose nevirapine in the study pregnancy. There were no significant differences in maternal CD4, viral loads or age in either group.
In the retrospective group of 41 nevirapine-naive and 59 nevirapine-experienced women, transmissions occurred in 17.1% and 11.8% of infants respectively. In the prospective group of 63 nevirapine naive-and 38 nevirapine-exposed women, the rates were 17.5% and 18.4% at 6-9 months. The hazard ratio for infant infection of nevirapine-naive vs -experienced mothers, adjusted for viral load, maternal age, CD4 and breastfeeding duration, was HR: 2.94 [95% CI: 0.55-15.55].
The authors found no significant differences in transmission rates from 201 infants born to nevirapine-naive and -exposed HIV positive Ugandan women. Dr Bakai suggested that the results are reassuring and provide evidence that use of single dose nevirapine in subsequent pregnancies remains an effective option in resource limited settings where more complex regimens are not yet feasible.
He also noted that these findings are consistent with those presented in a poster authored by Dr Martinson and co-workers combining data from the Soweto group and with those from the DITRAME or MTCT-Plus programmes in Abijan .
In the Abidjan group (n=41), women were enrolled prospectively and received single dose nevirapine in combination with either short course AZT, or short course AZT/3TC, in both pregnancies. Women in the Soweto group (n=120) were predominantly clade C whereas CRF02 was most common in Abidjan. Age and CD4 were similar in both groups. There were more C-sections in the Soweto group (21% in first and second pregnancies vs 2% and 3% in first and second pregnancies respectively).
At time of evaluation, HIV status data were available for 122 infants. Transmission rates were 10.9% and 13.2% after the first pregnancy and 13.5% and 2.9% after the second pregnancy in Soweto and Abidjan.
In a pooled sensitivity analysis, rates were 21.5% in the first pregnancies and 11.8% in the second pregnancies. In this analysis, 4/144 (2.7%) transmitted in both pregnancies. The authors also reported that 28.6% of women with <12 months between deliveries transmitted vs 7.7% whose inter-delivery time was >12 months (p=0.032).
Dr Martinson wrote: 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. Despite progression of disease between pregnancies, women who transmitted HIV to their infant in the first pregnancy do not necessarily transmit to their subsequent infant. No alteration in guidelines should be considered for the use of single dose nevirapine alone or in combination in women attending the prevention of MTCT programme a second time.
Although there is increasingly a move to co-prescribe dual NRTI therapy for 1 week with sdNVP to reduce the risk of NVP Resistance associated mutations this is not always possible. It is well documented that the frequency of virus with these mutations wanes with time and common-sense suggests that sdNVP prescribed in a subseqeunt pregnancy will be effective as the circulating virus will be predominantly wild type. The two studies presented, despite their obvious limitations provide supporting evidence although it will be important to determine further whether a minimum gap between pregnancies should be recommended.
- Martinson N, Pumla L, Morris L et al. Effectiveness of single-dose nevirapine in a second pregnancy. 12th CROI, 22-25 February 2005, Boston. Abstract 103.
- Eure C, Bakaki P, McConnell M et al. Effectiveness of repeat single-dose nevirapine in subsequent pregnancies among Ugandan women. 13th Conference on Retroviruses and Opportunistic Infections, 5-8 February 2006, Denver, Colorado, 2006. Abstract 125.
- Martinson N, Ekouevi D, Gray G et al. Effectiveness of single-dose nevirapine in consecutive pregnancies in Soweto and Abidjan. 13th Conference on Retroviruses and Opportunistic Infections, 5-8 February 2006, Denver, Colorado. Abstract 722.