1. Atazanavir Use in Pregnancy : a report of 33 cases St George’s Hospital South West London HIV & GUM Clinical Services Network Macky Natha 1, Phillip Hay 1, Graham Taylor 2, Gary Brook 3, Liat Sarner 4, Laura Cunningham 5, John Watson 6, Chris Wood 7, Jane Anderson 8, Annemiek de Ruiter 9 : Perinatal Pregnancy Group London UK St Georges Healthcare NHS Trust 1, Imperial College London 2, North Middlesex University Hospital NHS Trust 3, Barts and the London NHS Trust 4, Newham University Hospital NHS Trust 5, Mayday Healthcare NHS Trust 6, North-West London Hospitals NHS Trust 7, Homerton University Hospital NHS Foundation Trust 8, Guy’s and St Thomas’ NHS Foundation Trust 9 Background  Atazanavir (ATV) has been approved for use in Europe in treatment-experienced HIV patients since March 2004. However, the use of atazanavir in pregnancy remains unlicensed.  In the developed world, most HAART regimens used during pregnancy include a protease inhibitor. There are limited data on the use of atazanavir in pregnancy.  Atazanavir is labelled category B in pregnancy and there have been concerns about infant hyperbilirubinaemia with use of this drug in pregnancy.  Despite this, atazanavir is increasingly used in pregnancy, either when women conceive on therapy, or when it is initiated in pregnancy due to adherence, resistance or tolerability issues. Results 31 women were identified with a total of 33 pregnancies. There were 2 miscarriages, at 12 and 16 weeks respectively. 1 woman is still pregnant. All but 2 women were taking the 300mg/100mg ATV/RTV dose. 20 women conceived on ATV. At first antenatal visit, these women had an median VL of 98 c/ml (range <50-101454 c/ml). Their median CD4 count was 262 (range 61-660) x 10 9 /l. 10 women initiated ATV at a median of 22 (range 5-33) wks gestation. At first antenatal visit, they all had a VL of <50 c/ml and a median CD4 count of 270 (range 151-930) x 10 9 /l at baseline. Pre-treatment serum bilirubin and ALT were within normal limits. At delivery: Median VL and CD4 counts were <50 c/ml (range 50-28189 c/ml) and 269 (range 67-910) x 10 9 /l respectively. 23/30 women had an undetectable viral load. At delivery: Median maternal bilirubin level was 30 (range 4-76) umol/l [1.8 (range 0.2-4.4) mg/dL] and 23/26 mothers had a raised bilirubin (>17umol/l [>1mg/dL]). 19 mothers had ATV concentrations measured, performed at a median of 30 weeks gestation. 16 were taken in the 3 rd trimester and the mean trough ATV concentration was 373 mg/l. All but two were above the recommended therapeutic concentration of 100 mg/l. 29 infants were born at a median of 38 weeks gestation. Mean birth weight was 2894g (range 1080-4050g) and median infant bilirubin levels were 71 (range 10-191) umol/l [4.2 (range 0.6-11.2) mg/dL]. 3 infants had ATV concentrations measured within 24 hours of birth, showing levels of 189, 129 and 66 mg/l, respectively. The mother of the last infant stopped all her ARVs 2 weeks before birth. No infants required phototherapy and no birth defects were detected. The median time since delivery is 12 months (range 1-26 months) and all infants are thus far HIV uninfected. Contact Information Dr Macky Natha Courtyard Clinic St Georges Hospital London UK SW17 0QT 020 8725 3355 macky_natha@yahoo.co.uk Demographicsn=31 Age, years (range)31.9 (22-40) Ethnicity Black African27 Black Caribbean3 White1 HIV risk factor Heterosexual31 CDC class A18 C (CD4<200)13 Hepatitis B/C co-infection Hepatitis B1 Hepatitis C0 Median time since HIV diagnosis5 (0-16) years (range) New HIV diagnoses4 Methods A retrospective case notes review was performed on all women who were receiving atazanavir in pregnancy from nine London HIV units up to February 2007. Data were collected on maternal demographics, CD4 count, viral load, liver function tests, toxicity and plasma atazanavir concentrations. Infant data collected included birth weight, serum bilirubin, use of phototherapy and where available, HIV status at 6 months. Adverse events were also recorded in both mothers and infants. Conclusion To our knowledge this is the largest reported case series of the use of atazanavir in pregnancy. Atazanavir was well tolerated in our cohort and most women had good immunological and virological responses. Maternal plasma levels, where measured, were adequate. No early infant morbidity as a result of in utero exposure to atazanavir was demonstrated and all infants are thus far HIV uninfected. Results n Previous AZT monotherapy9 Previous ARV therapy27 Resistance Nil12 Single class2 Dual class7 Triple class2 Reason for ATV use Pt request for od regime9 Intolerant of LPV7 Resistance test5 Other 6 Nucleoside/Nucleotide Background Truvada11 TDF/ddI5 Kivexa4 Combivir4 TDF/3TC3 Other 3 Mode of delivery Elective CS19 Emergency CS9 Planned SVD2 Poster Number : 750 Mean laboratory values during pregnancy CD4 (x 10 9 /l)VL (c/ml)Bilirubin (umol/l)TDM (mg/l) 1st Trimester 201 n=15 range 10-473 42777 n=14 range 50-245800 19 n=14 range 6-41 2nd Trimester 273 n=21 range 40-930 1221 n=21 range 50-13500 28 n=21 range 4-76 435 n=3 range 250-589 3rd Trimester 322 n=25 range 67-910 1575 n=28 range 50-28189 37 n=23 range 4-76 373 n=16 range 71-1136 Mean laboratory values during pregnancy