No increase in adverse pregnancy outcomes in Thai women receiving nevirapine-containing HAART
Polly Clayden, HIV i-Base
There have been concerns that use of HAART in pregnancy may be associated with increased adverse pregnancy outcomes. There have been conflicting data from the developed world and few data from developing countries to support this association.
Nittaya Phanuphak and coworkers from Thailand presented findings from a chart review of data from a pregnant cohort between January 2003 and September 2005.
Until April 2004, the Thai Red Cross AIDS Research Centre MTCT reduction regimen was short course AZT and single dose nevirapine. After April 2004, all HIV positive pregnant women received AZT/3TC/NVP irrespective of CD4 count. Pregnant women initiated therapy as early as either 14 or 28 weeks, depending on whether baseline CD4 count was <200 or >200 cells/mm3 respectively.
There were 460 pregnancy outcomes for 460 women. The mean duration on ART was 6.5 weeks in the AZT + single dose nevirapine group and 12.2 weeks in AZT/3TC/NVP group.
The authors explained that limited data in women on AZT + sdNVP with low CD4 counts meant that they could only compare the effect of ART regimens among women with high CD4 counts.
Among AZT/3TC/NVP group BMI <24.3 (RR = 3.7, 95%CI 1.1 to 12.4) was a risk factor for LBW. Older age was a risk factor for preterm birth (RR=1.1, 95% CI 1.0-1.2). Neither remained significant after multivariate analysis.
The authors wrote: At least among women with high CD4 cell counts, NVP-based ART used in HIV-infected pregnant women was not associated with increased incidence of adverse pregnancy outcomes as compared with AZT + sdNVP. With the potential of having higher effectiveness in preventing mother to child transmission of HIV while causing lower risk of NVP resistant mutations both in women after delivery and HIV-infected babies, NVP based HAART should be considered as a possible option for PMTCT in the developing world.
Table 1: Pregnancy outcomes
|Pregnancy outcomes||AZT/SD NVP||AZT/3TC/NVP||RR (95% CI)|
|CD4<200 n=2||CD4>200 n=64||Total n=66||Total n=378|
|LBW||0||8.1||7.8||19.8||13.4||15.3||1.5 (0.9-2.4)||0.6 (0.2-1.5)|
|Preterm||0||15.6||15.2||21.7||12.9||15.6||0.9 (0.8-1.0)||1.0 (0.9-1.1)|
|Stillbirth||0||1.6||1.5||3.5||1.5||2.1||1.0 (0.9-1.0)||1.0 (1.0-1.0)|
|Neonatal death||0||0||0||0||1.1||0.8||1.0 (0.9-1.0)||1.0 (1.0-1.0)|
LBW = Low birth weight <2500g, TR = Transmission rate, Preterm birth =37 weeks
Whether HAART, particularly PI-containing HAART, is associated with increased pre-term delivery (PTD), low birth weight (LBW), gestational diabetes mellitus (gDM) or pre-eclampsia (PET) is a contentious issue. Data from Europe have tended to support an association, whereas data from North America do not.
This study finds no increased incidence of LBW and PTD, in a Thai population with CD4 counts >200 cells/mm3, in patients receiving a HAART regimen, consisting of zidovudine, lamivudine and nevirapine, from 28 weeks compared to a similar cohort exposed only to ZDV monotherapy from 28 weeks with sdNVP in labour.
It would be inappropriate to extrapolate these findings to other settings or other combinations, however it is of interest to note that having a CD4 count below 200 cells/mm3 doubled the risk of low birth weight (RR 2.1) and increased the incidence of PTD by almost 50%. It is impossible to know whether this relates to the more advanced immune suppression or to the longer duration of therapy, which in these mothers was commenced from 14 weeks.
Phanuphak N, Apornpong T, Teeratakulpisarn S et al. Pregnancy outcomes after combined ART or short-course AZT with single-dose nevirapine in Thai women with high and low CD4 cell counts. 13th CROI. Denver. Abstract 712.