Raltegravir Safe and Effective in Pregnancy in Small French Study
Raltegravir was safe and effective in pregnancy and for exposed infants in a small French study presented at the 53rd ICAAC.1
These data were presented by Vincent Jeantils and are from an ongoing study of mother-infant pairs conducted at Jean Verdier Hospital in Bondy, France.
All HIV positive pregnant women at this centre are referred to a multidisciplinary team including infectious disease specialists, obstetricians and pediatricians. Complete blood, CD4 cell count, viral load, transaminase, creatinine, and glucose is assessed monthly.
The study, which started in 2008, included 31 pregnant women with a median age of 31 years (range 18 to 44). Two women were coinfected with hepatitis C and three with hepatitis B.
Five (16%) women had started raltegravir-based regimens before they became pregnant and remained on them, three (10%) and 23 (74%) women started raltegravir in the second and third trimesters respectively.
Five women started raltegravir due to side effects with other antiretrovirals, 19 because of poor adherence with a previous regimen and two because of late diagnosis.
Their median CD4 count when starting raltegravir was 442 cells/mm3 (range 155 to 786) and viral load 17,765 copies/mL (range 61 to 114,638). Median raltegravir duration was 71 days (range 3 to 287). Median viral load before delivery was 41 copies/mL (range 0 to 641). Six women (19%) had detectable viral load (>40 copies/mL) at delivery, ranging from 45 to 641 copies/mL.
The investigators reported no biological abnormalities were observed in the 32 infants (one set of twins). Their median gestation age at delivery was 38 weeks. Fifteen women had vaginal deliveries and the remainder had planned or emergency caesareans. Almost all women (30/31) received intravenous AZT during labour.
The median weight of the infants was 3100 g (range 2120 to 4030) and median height was 48 cms (45 to 52), with a median Apgar score of 9.6 out of 10. All infants received four weeks of antiretrovirals: 23 AZT alone, four received two and five received three-drug prophylaxis. The investigators did not observe adverse reactions to treatment in the infants and 93% have tested HIV negative at six months.
At delivery the investigators performed a pharmacokinetic evaluation of maternal and cord blood in a subset of 16 cases. The median maternal raltegravir concentration was 10 to 270 ng/mL and median cord blood concentration was 5 to198 ng/mL. The median cord blood to maternal ratio was 3.48 (range 1 to 7.6).
The children in this study will be followed for six years, so far the longest has been five but no adverse outcomes have been reported yet.
BHIVA pregnancy guidelines recommend raltegravir: as a component of a three or four drug regimen for women presenting late (>28 weeks) with viral load greater than 100,000 copies/mL or unknown, and with AZT/3TC plus a single dose of nevirapine for women presenting in labour.2 The guidelines also do not recommend switching regimens for women who conceive on stable ART -- so similar scenarios to these described could be expected in the UK.
In this study 61% women also received a protease inhibitor, all but one woman received intrapartum IV AZT during delivery, and all infants four weeks of prophylaxis, so isolating the effect of raltegravir is tricky but there appears to be minimal HIV transmission.
Raltegravir has high first and second phase viral decay, rapid placental transfer and pre-loads the neonate (giving therapeutic concentrations that are stable for several days after delivery), which make it seem a good candidate for use in pregnancy -- particularly for late presenters -- although we note in the BHIVA guidelines that no adequate, well controlled studies of raltegravir in pregnant women have been conducted.
That no birth abnormalities were observed in the 32 infants is consistent with the limited data submitted to the Antiretroviral Pregnancy Registry so far -- 3 defects in 119 infants exposed to raltegravir during the first trimester, and 6 in 109 during the second or third trimesters.3 Raltegravir is pregnancy category C.
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This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
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