Lopinavir and atazanavir in pregnancy: preterm delivery rates, infant outcomes and virological efficacy. Dr Melissa Perry Guy’s & St Thomas’ NHS Foundation Trust London United Kingdom

Townsend et al CROI 2013 poster 906

What we know? Excellent ART coverage Excellent PMTCT Preterm delivery concerns Drug or drug class? Timing of ART?

Lorenzi P, Spicher VM, Laubereau B et al. AIDS 1998; 12: F241–F247 Association between ART and PTD European Collaborative Study. J Acquir Immune Defic Syndr 2003;32: 380– 387. Association between ART and PTD Townsend CL, Cortina-Borja M et al AIDS 2007; 21: 1019– fold increased risk of PTD on ART - No association between PTD and PI- containing ART Townsend CL, Willey BA et al. AIDS 2009; 23: 519–524. Association between ART and PTD European Collaborative Study AIDS 2000; 14: 2913–2930. Association between ART and PTD - particularly marked in patients on PI’s European Collaborative Study. AIDS 2004; 18: 2337–2339. Association between ART and PTD - particularly marked in patients on PI’s Cotter AM, Garcia AG, Duthely ML et al J Infect Dis 2006; 193: 1195–1201. Association between ART and PTD - only if ART included a PI Schulte J, Dominguez K, Sukalac T et al Pediatrics 2007; 119: e900–e906. Association between ART and PTD - only if ART included a PI Tuomala RE, Shapiro DE, Mofenson LM et al. N Engl J Med 2002; 346: 1863–1870. No Association between ART and PTD Tuomala RE, Watts DH, Li D et al. J Acquir Immune Defic Syndr 2005;38:449–473. No Association between ART and PTD Kourtis AP, Schmid CH, Jamieson DJ, Lau J. AIDS 2007;21: 607–615 No Association between PTD and PI-containing ART Powis KM, Kitch D, Ogwu A et al. J Infect Dis 2011; 204: 506–514. Association between PI-based ART and PTD Kesho Bora Study Group, de Vincenzi I. Lancet Infect Dis 2011; 11: 171–180. No Association between ART and PTD

As per HIV treatment guidelines for non pregnant individuals - based on VL, CD4 & genotype Conceive on ART remain on the same ART* Commencing ART for maternal health start ART ASAP All women should commence ART by 24W* No recommended dose adjustments. Therapeutic drug monitoring - only consider.

In clinical practice: ritonavir-boosted lopinavir ritonavir-boosted atazanavir Two most commonly used PIs in pregnancy in the UK are ritonavir-boosted lopinavir and ritonavir-boosted atazanavir Our Question? Atazanavir or lopinavir Atazanavir or lopinavir in pregnancy?

Outcomes Pre term delivery Infant outcomes transmission birth weight phototherapy requirement birth defects Tolerability and viral response clinical and virological aspects

Retrospective case note review 9 London HIV specialist care centres All pregnancies atazanavir or lopinavir commenced on atazanavir or lopinavir or atazanavir or lopinavir conceived on atazanavir or lopinavir delivered 1 st Sept th Aug 2012

Results n=493 pregnancies Median age 33 years Ethnicity 81% Black African. HIV acquisition 97% through heterosexual exposure 0.6% from injecting drug use Hepatitis co-infection Hep B – 4% Hep C – 1%

Atazanavir Lopinavir Total number of patients:

NRTI Backbone AtazanavirLopinavir % on standard dose 88% 92%

Numbers of patients AtazanavirLopinavirTotal Conceived on Post conception Total

% of women who delivered <37W *8 percent (1 in 13) of general population UK live births are born preterm Atazanavir Lopinavir p-value Overall: 19 (13%) 40 (14%) ns Conceived on 11 (15%) 8 (12%)0.98 Post conception 16 (20%)24 (12%)0.12

Atazanavir Lopinavir Transmissions1 (0.7%)1 (0.4%) Overall MTCT rate: 0.5% % requiring phototherapy 2 (2%)2 (1%) Birth defects 3 (3%)2 (2%) (Conceived on) % <2500g birth weight 23 (15%) 40 (15%) Infant outcomes

Tolerability / toxicity Atazanavir Lopinavir Conceived on 2 (2%)5 (6%) Post conception5 (5%)24 (11%) 55% related to nausea & vomiting

Viral load decay ATV/r (despite the majority of women on ATV/r receiving the standard 300/100mg dose and co-prescribed tenofovir.) Atazanavir Lopinavir Gestation 20w 22w (at starting ART) % VL<=50 cps/ml 85% 81% 0.61 at delivery Median days VL <= 50 cps/ml 56days 43days 0.52

Conclusions Both regimens were successful in preventing MTCT ATV/rLPV/r No significant difference between ATV/r and LPV/r in preterm delivery rates infant outcomes tolerability and toxicity virological efficacy The PTD rates were comparable to those reported in previous studies and more favourable than others

Limitations Retrospective case note review Small case numbers Lacks power Limited scope for multivariable logistic regression analysis

Summary This is the first study comparing pregnancy outcomes between these two PIs. This study suggests both PI regimens at standard dosing are comparable in terms of virological efficacy, preterm delivery rates and infant outcomes.

Disclosure I have received travel grants from Abbott, Boehringer Ingelheim, ViiV, Gilead.

Authors & Affiliations Melissa Perry 1, Katie Conway 1, Caroline Sabin 2, Stuart Flanaghan 3, Ellen Dwyer 4, Stevenson J 4, Larissa Mulka 5, Anna McKendry 6, Elizabeth Williams 8, Alison Barbour 10, Sherie Roedling 6, Rimi Shah 7, Jane Anderson 3, Mette Rodgers 4, Chris Wood 8, Liat Sarner 9, Phillip Hay 10, Graham Taylor 5, Annemiek DeRuiter 1. 1 Guys and St Thomas NHS Foundation Trust. 2 Department of Infection and Population Health, Division of Population Health, UCL Medical School. 3 Homerton University Hospital NHS Foundation Trust. 4 Croydon University Hospital. 5 Imperial College Healthcare NHS Trust. 6 Central and North West London NHS Foundation Trust. 7 Barnet and Chase Farm hospital NHS trust. 8 The North Middlesex University Hospital NHS Trust. 9 Barts Health NHS Trust. 10 St Georges Healthcare NHS Trust

Questions?