The use of antiretroviral agents during pregnancy in Canada and compliance with North-American guidelines I. Boucoiran, T. Lee, K. Tulloch, L. Sauve, L. Samson, J. Brophy, M. Boucher and D. Money For and members of the Canadian Pediatric HIV Surveillance Program (CPHSP)
CONFLICT OF INTEREST DISCLOSURE The authors declare no conflicts of interest
Current Antiretroviral medications NRTI Abacavir (ABC) Didanosine (ddi) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4t) Tenofovir DF (TDF) Zidovudine (AZT, ZDV) NNRTI Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV) PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Saquinavir (SQV) Tipranavir (TPV) Pharmacokinetic Enhancers Ritonavir (RTV, /r) Cobicistat (COBI) Entry Inhibitor Enfuvirtide (ENF, T-20) Maraviroc (MVC) INSTI Raltegravir (RAL) Elvitegravir (EVG) Dolutegravir (DTG) 3 August 2015
North American HIV Perinatal Guidelines HHS US 2004 HHS US 2005 HHS US 2006 HHS US 2006 HHS US 2007 HHS US 2009 HHS US 2011 HHS US 2013 HHS US 2015 + Canada: CMAJ (2003), SOGC (2013)
First line antiretroviral regimens in pregnancy as per US HHS 2004 2015
Treatment as prevention
Research question How the use of antiretroviral therapy (ART) in pregnancy is influenced by evolution of perinatal and adult guidelines in Canada? Objectives: To describe trends in Canada for the use of ART in pregnancy To compare ART received at conception/1st trimester or initiated in pregnancy with North-American guidelines.
CPHSP: the Canadian Perinatal HIV Surveillance Program Since 1984 22 sites in Canada Collected data: demographics, antiretroviral exposure, HIV testing outcome of the infant. Data management and analysis provided by the Canadian Institutes of Health Research Canadian HIV Trials Network (CTN)
Methods Mother infant pairs included between 2004 and 2015 Exclusion criteria: No ARV in pregnancy (n=157) n = 2355 pregnancies (1839 women) ARV categorization according to: Available guidelines at the time of conception 2015 guidelines
Population Ethnicity Aboriginal Asian Black Latin American White
Population Time of HIV diagnosis 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Before conception First trimester Second trimester Third trimester Rate of transmission: 0.7%
Timing of antiretroviral initiation 80% 70% 60% 50% 40% 30% 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 At/before conception Second trimester Detectable VL at delivery First trimester Third trimester
Type of first antiretroviral regimen 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 NRTI NRTI+ NNRTI NRTI + unboosted PI NRTI + boosted PI NRTI + Integrase inhibitor Other combinations
Non prefered ARV as per available perinatal guidelines 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 At conception / first trimester Ever in pregnancy
ARV used in pregnancy classified as per 2015 perinatal guidelines 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Lack of safety data (DTG, EVG/COBI/TDF/FTC, FPV, MVC, COBI) Toxic/poor viral suppression (ABC/3TC/ZDV, d4t, ddi, IDV/r, NFV, RTV as a single PI, SQV/r, NVP) Recently approved (RAL, DRV/r or EFV)
Comments Moving practice Clinical practice advancing ahead of perinatal guidelines Limits No data on congenital anomalies and spontaneous abortion No genotype data
Conclusions A high number of HIV-infected women receiving ART at the time of conception tend to be treated with not preferred ART as per North-American perinatal guidelines. Concern in the context of the licensure of new ART medication: Principles of antiretrovirals selection in pregnancy should be considered when prescribing ART to women in reproductive age
Thank you
General Principles of Antiretrovirals Selection in Pregnancy Consider and discuss the benefits vs. risks of each ARV Concerns about specific ARVs during pregnancy Limited experience during pregnancy with newer ARVs ARV drug-resistance Gestational age at ARV initiation Increased volume of distribution / pharmacokinetics Adherence hyperemesis and substance use Interactions with other medications Ensure that at least 1 NRTI with high placental transfer is included in cart regimen for sufficient infant preexposure prophylaxis. Coordinate between HIV and OB specialists.
Antiretrovirals use in pregnancy Centre maternel et infantile sur le sida 923 pregnancies CHU Sainte-Justine, déc 2014 60 50 40 30 20 10 0-87 89 91 93 95 97 99 '01 '03 '05 '07 '09 '11 '13 Year of delivery NIL ZDV CD4 < 200 ZDV x 3 months #REF! DOUBLE TRIPLE MULTIPLE NPV / RAL added at the end of pregnancy
Timing of antiretroviral initiation 80% 70% 60% 50% 40% 30% 20% 10% 0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 At/before conception First trimester Second trimester Detectable VL at delivery Third trimester