Should criteria for initiation of HAART be revisited in pregnant women?
Polly Clayden, HIV i-Base
Increasing numbers of women are diagnosed in pregnancy. Two posters evaluated the impact of pregnancy on CD4 counts and suggest that absolute CD4 values may not be the best criteria by which to initiate HAART in pregnancy.
In 2004, for the first time, WHO recommended the use of HAART in pregnant women in resource limited settings for the prevention of mother-to-child transmission (MTCT) of HIV.
Didier Koumavi Ekouevi and co-workers caution: The eligibility criteria to initiate HAART do not take into account the specificities of pregnancy. In particular they raise the risk of increased risk of pre-term delivery and that use of nevirapine is no longer recommended for women with CD4 >250 cells/mm3. 
They report findings from a study to assess whether the variation of CD4 absolute count and percentage in prepartum and postpartum periods could have consequences on the decision process regarding HAART initiation in HIV-positive African pregnant women.
The group reviewed data from the ANRS 1201/1202 DITRAME Plus study, an open label cohort in Abidjan, C’ote d’Ivoire, to assess the efficacy of short course AZT for MTCT. CD4 count and percentage were measured by flow cytometry at 32 weeks of gestation and at months 1, 6, and 12 after delivery. Signed-rank test was used to compare the distributions of the CD4 absolute count and percentage values at the four time points.
Data were available for 229 women. At baseline, the median CD4 count was 355 cells/mm3 (IQR: 225-494 cells/mm3) and the median CD4 percentage was 24.9% (IQR: 18.8-31.7%), 15% of women had CD4 count <200 cells/mm3 and 13 % had CD4 percentage <15%.
At one month after delivery, the median CD4 count was 495 cells/mm3 (vs baseline p<0.001), the median CD4 percentage was 26% (vs baseline p= 0.06), 7.0% of women had CD4 count <200 cells/mm3 (vs baseline p= 0.007), and 12% of women had CD4 percentage <15% (vs baseline p= 0.89).
When combining the CD4 count and the WHO clinical stage, the proportion of women eligible for HAART by WHO 2003 criteria was 28% at baseline but only 15% at one month after delivery (p <0.001) or 31% against 17% (p<0.001) with WHO 2005 criteria.
They reported a significant increase in absolute CD4 count post partum and a decrease in the proportion of women with <200 cells/mm3 but in comparison CD4 percentage values were stable.
The investigators concluded: It may be important to define specific conditions for HAART initiation in pregnant women in resource limited settings. We suggest using exclusively CD4 percentage instead of CD4 absolute count when considering HAART initiation in pregnant women.
Similar recommendations came from Fiona Mulcahy and co-workers from St Jamess Hospital, Dublin, Ireland who reported findings from a study to quantify the effect of pregnancy on the numbers of circulating CD4 cells. 
Data from 284 pregnancies in 198 HIV positive women over a 4-year period were assessed. Pre-conception (mean 10 weeks prior to conception, range 4 to 24 weeks), post conception (mean 13 weeks, range 4 to 24 weeks), and postpartum (mean 10 weeks, range 4 to 24 weeks) CD4 counts were available in 85 of these pregnancies.
Sixty of the women were African and 25 were Caucasian. The CD4 count declined in 77 of 85 (91%) of pregnancies by a mean of 21% (p = 0.0005). 50 of the women were receiving ART prior to conception and 35 women initiated treatment only after the 24th week of pregnancy to prevent MTCT.
The mean decline in CD4 count in women receiving treatment prior to conception was 13 % (mean CD4 preconception 485 cells/mm3, post conception 410 cells/mm3, p = 0.003) vs 27% (mean CD4 count pre-conception 575 cells/mm3, post conception 421 cells/mm3, p = 0.0001) in those not receiving treatment. Treatment prior to conception significantly reduced the fall in CD4 cells (p= 0.003). There was no difference between the CD4 counts pre-conception and post-partum CD4 count in either group and no difference in the pregnancy-induced fall in CD4 count between the different ethnic groups.
The authors wrote: Pregnancy induces a significant fall in CD4 counts in HIV-positive women and the magnitude of this fall is greater in the absence of ART. Commencement of long-term ART based on these values will result in over treatment in a significant number of women. The guidelines for the commencement of long-term ART in pregnancy should be reviewed.
The studies by Ekouevi et al and Mulcahy et al are timely reminders, as HAART becomes more widely available, that CD4 counts physiologically decline during pregnancy whilst CD4% remain stable. The assessment of need for continuing HAART post-partum must consider the effect of haemodilution on CD4 absolute counts and CD4% should be used both in making this assessment and in reassuring pregnant women that their immune system has not dramatically deteriorated.
- Ekouevi D, Inwoley A, Tonwe-Gold B et al. Criteria for HAART should be revisited in HIV-infected pregnant women in resource limited settings. 13th Conference on Retroviruses and Opportunistic Infections, 5-8 February 2006, Denver, Colorado. Abstract 704a.
- Mulcahy F, Wallace E, Woods S et al. CD4 Counts in Pregnancy Do not Accurately Reflect the Need for Long-term HAART. 13th Conference on Retroviruses and Opportunistic Infections, 5-8 February 2006, Denver, Colorado. Abstract 704b.