Feedback from Pregnancy research group

1. NSHPC Feedback from Pregnancy research group UK CHIC / UK HIV Drug Resistance Database Meeting, 2 July 2010 Pregnancy Group: Jane Anderson, Loveleen Bansi, Susie Huntingdon, Marie-Louise Newell, Caroline Sabin, Graham Taylor, Claire Thorne, Pat Tookey

2. Background • Complex and incompletely understood relationships exist between pregnancy, HIV disease progression and ART used for PMTCT and/or treatment • Unique considerations apply to use of ART in pregnancy, reflecting the dual goals of preventing MTCT and maternal disease progression plus the need to consider the developing fetus • Increasing numbers of HIV-infected women in the UK are having children • Around three-quarters of pregnancy reports for HIV-infected women in the UK/Ireland in 2009 were for women aware of their HIV status prior to pregnancy

3. Linkage project • Research theme in current CHIC grant is the impact of ART received in pregnancy on the health of HIV-infected women • A linkage project has been established between the UK CHIC Study and the UK National Study of HIV in Pregnancy and Childhood to establish which women in CHIC have been pregnant Rationale • CHIC does not collect information on pregnancy • NSHPC collects information on pregnant HIV-infected women but not on maternal HIV-related outcomes post-natally • Linkage of data within the two studies’ datasets will allow a range of research questions to be addressed with respect to pregnancy, ART and long-term outcomes

4. Key research questions • What are the long-term outcomes of women exposed to antenatal ZDV monotherapy? • Is there any negative impact on resistance development in future treatment, or in PMTCT for subsequent pregnancies, of receiving short-term ART (START) during pregnancy? • What is the risk of viral load rebound during pregnancy and is this higher than the risk in non-pregnant women? Is there is a difference in rebound rates post-pregnancy between women with and without exposure to START? • What are the treatment outcomes among women with exposure to START who restart ART at a later stage when they require it for their own health? • What is the long-term impact on the woman of sequential courses of START during subsequent pregnancies? • Are ALT levels different among women starting HAART during pregnancy compared with women starting HAART prior to or after pregnancy? Are pregnant women more likely to discontinue treatment due to suspected liver toxicity than non-pregnant women?

5. NSHPC National Study of HIV in Pregnancy and Childhood • A collaboration between the Institute of Child Health, the Health Protection Agency Centre for Infections & Health Protection Scotland • Established in 1986 (AIDS in children) and extended to include HIV in pregnancy 1989 • Active reporting systems: comprehensive surveillance of all diagnosed obstetric and paediatric cases in the UK and Ireland • Pregnant women known to be HIV-infected are reported via Royal College of Obstetricians and Gynaecologists • Paediatric HIV cases and children born to infected mothers are notified through the British Paediatric Surveillance Unit of the Royal College of Paediatrics and Child Health. • MREC and PIAG approved; case ascertainment >95% • PI: Pat Tookey; NSHPC team based at ICH

6. Linkage process • Women in CHIC linked to women delivering after 01/01/1996 in theNSHPC dataset using date of birth • CHIC women with an exact CD4 date match with NSHPC women, with the same CD4 count (+/- 10 cells/mm3) and seen at the same place or with the same HIV diagnosis date → matches • Women with exact CD4 date match but not meeting the above criteria → manual check → matches • Women with a CD4 date match for month/year → match if same CD4 count or same centre or same date of HIV diagnosis • All other patients with a CD4 date match for month/year → manual check → matches • Women without CD4 count match/missing CD4 counts → match if same month/year of HIV diagnosis and same hospital location; manual checks if women only met one of these criteria • For ~60% of matched women, this was on the basis of exact or mm/yy CD4 count date and CD4 count +/- 10 cells/mm3

7. Linkage results • Linkage has been carried out on 2008 and 2009 CHIC datasets • To date, 1838 (21%) women in CHIC dataset have been classified as having had a pregnancy • Descriptive analyses carried outto date, to characterise pregnant women in CHIC • Results presented at BHIVA 2010

8. Preliminary results • Amongst the 1838 women, 821 (45%) received HIV-related clinical care before their first pregnancy • Most were infected heterosexually (88%) and 69% were of black-African ethnicity • Median age at delivery was 33 years (IQR: 28, 36) • Median CD4 count at start of pregnancy was 382 (269, 540) cells/mm3 • Of women with viral load measured <90 days before conception, 53% had a VL >50 copies/ml overall, and 27% of those on ART • 54% (440/821) women were receiving ART at conception • 77% had been on ART for >1 year • 20% conceived on EFV • 54% on NNRTI-regimen, 21% on PI/r-regimen

9. Switching regimens in pregnancy • 35% (155/440) women conceiving on ART switched regimen before delivery • Of women who switched, 24% were on EFV at conception and 18% were on TDF • Median CD4 count at switch was 315 cells/mm3 (IQR 201,490) and 42% had detectable HIV RNA (>50 copies/ml) Time to switching ART after conception Probability: 22% by 3 months and 33% by 6 months gestation

10. 440 women conceiving on ART Delivery • 12 (3%) had stopped ART before delivery • Median delivery CD4 count among women on treatment was 400 cells/mm3 (IQR 280,530) • 19% of women with VL available 90 days before delivery had detectable VL (>50 copies/ml) (c.f. 27% before conception) Post-natal period • Probability of switching ART regimen by 12 & 24 months after delivery was 41% and 61% respectively • 3% discontinued ART completely in the first 12 months after delivery

11. Summary • Just over half of pregnant women in CHIC did not receive HIV-related clinical care prior to their first pregnancy • Of the womenreceiving pre-pregnancy HIV-related clinical care, nearly half were on ART at conception • Of the group of women conceiving on ART: • 20% were on EFV at conception, despite guidelines recommending that women planning a pregnancy change from EFV • One-third switched therapy during pregnancy (toxicity concerns as well as treatment failure) • Nearly half had switched ART regimen 12 months after delivery • A small proportion (6%) discontinued ART during pregnancy or within 12 months after delivery