Principal Investigator - Dr. Rebecca Zash, MD

Study Objectives: General and Specific

• Aim 1. To establish the role of hypertension in adverse pregnancy outcomes among HIV-infected women on antiretroviral therapy (ART). We will determine whether HIV-infected pregnant women have more severe hypertension, earlier onset of hypertension, or poorer response to antihypertensive treatment and also use formal mediation analysis to determine if hypertension mediates the relationship between 1) HIV and 2) specific ART regimen and preterm delivery, stillbirth and SGA.
• Aim 2. To elucidate the role of progesterone and chronic inflammation as underlying mechanisms of adverse pregnancy outcomes among HIV-infected women on ART. We will investigate whether low progesterone and elevated markers of chronic immune activation (sCD14, CRP, IL-10, IL-6) are associated with: (a) HIV-infection in pregnant women; (b) gestational hypertension or preeclampsia; (c) specific ART regimens among HIV-infected pregnant women. 

Secondary Objectives

• To evaluate the accuracy of blood pressure measurements taken during routine prenatal care.
• To evaluate the accuracy of antenatal care medical records.
• To explore differences in pregnancy dating using LMP vs. ultrasound.
• To describe the cascade of care for pregnant hypertensive women in Botswana.
• To evaluate the impact of nadir CD4 count and pregnancy CD4 count adverse pregnancy events and birth outcomes.
• To evaluate the impact of viral load on adverse pregnancy events and birth outcomes.
• To understand the risk factors for adverse birth outcomes among women on ART.
• To evaluate STDs and other infections as risk factors for adverse birth outcomes.
• To evaluate urine protein as a risk factor for adverse birth outcomes and the development of hypertensions and pre-eclampsia.
• To evaluate risk factors for low progesterone and makers of chronic immune activation among HIV-uninfected pregnant women.
• To evaluate weight gain in pregnancy by ART regimen.
• To evaluate the association between self-reported nutritional status, upper arm circumference and weight with adverse pregnancy events and birth outcomes 

Study Design:

Aim 1: Data analysis of already-collected, anonymized data
Aim 2: Prospective observational cohort

Study Population and Size: 

• Aim 1: We will include data collected in Tsepamo from August 2014- August 2018 an expected number of approximately 93,000 births.
• Aim 2: We plan to enroll up to 400 pregnant women for participation in this study, approximately 92 HIV-uninfected and approximately 308 HIV-infected

The sample size will be as follows;

• Aim 1: We will include data collected from Tsepamo, up to 100,000 births.
• Aim 2: We will enroll up to 400 pregnant women (92 HIV-uninfected, 216 HIV infected already on ART and 92 HIV infected not yet on ART).

Study Duration: 48 months

Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH/NICHD).