Dorina Onoya1, Tembeka Sineke1, Alana Brennan1,2, Matt Fox1,2 Timing of pregnancy among HIV positive women and postpartum risk of virologic failure and loss to follow up in South Africa Dorina Onoya1, Tembeka Sineke1, Alana Brennan1,2, Matt Fox1,2 1Health Economics and Epidemiology Research Office, University of the Witwatersrand, South Africa 2Department of Global Health, Boston University School of Public Health, USA

Background All pregnant women are initiated on lifelong ART upon HIV diagnosis and many are conceiving while already on ART Long term antiretroviral therapy (ART) success depends on the ability to attain and maintain virologic suppression. Women generally struggle to adhere to ART and remain in care after delivery There is limited information on postpartum virologic outcomes. Very limited data on association between timing of pregnancy and the risk of postpartum virologic failure or disengagement from ART. HIV burden continues to be a significant problem particularly among South African women of child bearing age and is an important contributor to maternal mortality (1).

Objectives To examine effect of timing of pregnancy in relation to ART initiation on: The risk of virologic failure in the first 2 years postpartum among HIV positive women. The risk of loss to follow up (LTFU) in the first 2 years postpartum among HIV positive women. prevalent pregnancy at ART initiation compared to women with incident pregnancy after ART initiation.

Methods Study design and site: Restrospective analysis of routinely collected medical records of HIV infected women initiated on ART from 2004 to December 2013 at 10 public sector ART clinics in Johannesburg, South Africa . Inclusion criteria: HIV positive adult women of childbearing age at ART initiation (18 to 49 years old) Postpartum women with a pregnancy resulting in a live birth Controls were women with no recorded pregnancy matched to postpartum women on age at ART initiation and time on ART. Follow up period: Person time accrued from the date of delivery (baseline) for postpartum women and their matched controls. Women were followed until the outcome of interest, the last date seen at the clinic during the first two year or 31 December 2015 (administrative censoring). Women with no pregnancy were followed for 2 years post ART initiation Women who were initiated during pregnancy were followed 2 years postpartum and for those with an incident pregnancy and 2 years after the first pregnancy on ART Limited pregnancy information

Methods Primary outcome: Virologic failure, defined as having two consecutive viral load measurements >1000 copies/ml, at least 3 months after delivery Secondary outcome: Loss to follow up, defined as being more than 3 months late for a scheduled appointment. Primary exposure Timing of first recorded pregnancy (Control- never pregnant, prevalent pregnancy – Initiated ART during pregnancy, incident pregnancy – conceived on ART). Statistical analysis Kaplan–Meier curves were used to compare progression to the first virologic failure or LTFU event Cox Proportional Hazards modelling were used to examine predictors of the outcomes of interest. The risk of virologic failure and LTFU were assessed separately Potential confounders for the association include: i) demographic variables; ii) baseline clinical and laboratory variables including body mass index (BMI), CD4 counts, haemoglobin and;

Results 6971 were included, 3068 (44.0%) controls, 1968 (28.3%) incident pregnancies and 1935 (27.8%) prevalent pregnancies (3219 were excluded due to missing viral load data). 2 years post-partum ( for those pregnant) or 2 years after ART initiation for those never pregnant

Postpartum risk of virologic failure Overall 563 (8.1%) had a virologic failure at a rate of 5.0 per 100 PY (95% CI: 4.6-5.5). Controls: 5.0 per 100PY, 95% CI: 4.5-5.7 Incident pregnancy: 5.7 per 100PY, 95%CI: 5.0-6.6 Prevalent pregnancy: 4.2 per 100PY, 95% CI: 3.5-5.0

Rates of virologic failure postpartum (stratified by CD4) Rates of virologic failure increases with time virologic failure increases much faster for those with prevalent pregnancy for those with CD4 <350 For those with CD4 > 350, the virologic failure increases much faster for those with incident pregnancy

Predictors of postpartum virologic failure Incident pregnancies on ART Time on ART before delivery did not predict virologic failure. Prevalent pregnancy at ART initiation Higher CD4 count at delivery was protective (aHR 0.3 (0.2-0.6) CD4≥350 cells/µl group compared to CD4<100 cells/µl Variable Category Reference aHR (95% CI) Age 30-39 Under 25 0.6 (0.3-1.0) CD4 at delivery >=350 <100 0.2 (0.1-0.3) Hb at delivery Anaemic Normal 1.5 (1.1-2.1) WHO stage at delivery Stage 3 Stage 1 1.6 (1.1-2.5) VL failure in pregnancy Yes No 2.1 (1.5-3.0)

Postpartum risk of being LTFU by 24 months 1645/6971 (23.6%) patients were LTFU by 24 months of observation, at a rate of 8.6 per 100PY (95% CI: 8.2-9.0). Controls 23.6%, 8.4 per 100PY (7.8-9.1) Incident pregnancy 19.4%, 6.5 per 100PY (5.9-7.2) Prevalent pregnancy 27.9%, 11.2 per 100PY (10.3-12.2)

Median months to failure/LTFU

Predictors of being LTFU at 24 months postpartum Incident pregnancies on ART The risk of postpartum LTFU was not associated with age, employment status, CD4 level or time on ART before delivery. Variable Category Reference aHR (95% CI) Level of education Secondary school Primary school 1.6 (1.0-2.5) Clinic type Primary health care Hospital based clinic 1.7 (1.3-2.1)   Non Governmental Organisation 0.7 (0.5-1.0)

Predictors of being LTFU at 24 months postpartum Prevalent pregnancy at ART initiation Variable Category Reference aHR (95% CI) Age 30 to 39 years under 25 years 0.8 (0.6-1.0) Level of education Secondary school Primary school 1.4 (1.0-2.1)   Grade 12 0.7 (0.5-1.0) Clinic type Non Governmental Organisation Hospital based clinic 0.5 (0.4-0.6) Occupation Unemployed Employed 1.2 (1.0-1.4) Antenatal ART ≥ 7 months ≤ 3months 0.4 (0.3-0.7)

Conclusion Young women who conceive on ART are at higher risk of postpartum VL failure but are more likely to remain in care Virologic failure seem associated with poor health state at delivery which may be the results of poor outcomes during pregnancy. Targeted adherence and support interventions to ART experienced women at risk of adverse outcomes postpartum

Conclusion Women who initiate ART during pregnancy are more likely to disengage from care postpartum Low risk of postpartum virologic failure – don’t stay in the system long enough for the failure to be recorded Those with longer antenatal ART exposure are less likely to disengage Need to strengthen the adherence and support program among women diagnosed in third trimester or at delivery

Acknowledgements Data teams Right to Care Health Economics & Epidemiology Research Office