**1. Problem Identification**

### *Maternal Mortality and Hypertension in South Africa*

The adoption of the Millennium Development Goals from 1990–2015 led to a decline in global maternal mortality by 44%; however, South Africa (SA) was unable to reach the target set by the United Nations (Millenium Development Goals, 2015 Report). South Africa has since embraced the Sustainable Development Goals 2016–2030 to reduce its maternal mortality ratio to <70 deaths/100,000 live births [1]. Despite a decline in maternal deaths from human immunodeficiency virus (HIV) infection and obstetric hemorrhage over the period 2008–2016, no change in mortality emanating from hypertensive diseases in pregnancy (HDP) occurred [2]. In fact, deaths from HDP is the commonest direct cause of maternal mortality as reported by the Confidential Report of Saving Mothers in 2017 [2]. Hypertensive diseases in pregnancy account for 18% of all maternal deaths in SA [3]. In developed countries, HDP has a prevalence of 5–10% [4]; however, in developing countries, it occurs more

frequently. The incidence of preeclampsia (PE) was 12% amongs<sup>t</sup> all primigravidae who delivered at a large regional hospital in SA [5]. In SA, PE significantly a ffects both the mother and perinatal morbidity and death. The World Health Organization (WHO) reported that this multisystem pregnancy disorder accounts for 1.6% of maternal deaths in developed countries [6] and 1.8–16.7% in developing countries such as South Africa, Egypt, Tanzania, and Ethiopia [7,8].

#### **2. Human Immunodeficiency Virus Infection in South Africa**

HIV infection is a grave public health challenge globally. Sub-Saharan Africa constitutes 56% of the HIV-infected global population [9]. In 2017, women accounted for a disparate 59% of new adult HIV infections (>15 years) [10]. In SA, 13.1% of the total population is HIV-positive, of which 20% involves women in their childbearing age (15–49 years) [11]. Greater than 40% of the global HIV-infected population includes adults residing in the region of KwaZulu-Natal (KZN) [9]. Moreover, the Antenatal HIV and Syphilis Surveillance Report indicates that >37% of antenatal attendees in KZN province are infected [12]. Hence, healthcare professionals providing maternity care are challenged with a double burden of HIV infection and HDP.

The association between HIV infection and PE emanates from the di fferent immune responses [13]. In light of the pervasive nature of both conditions in KZN, this association warrants urgen<sup>t</sup> investigation. Notably, in SA, our group performed extensive research on the e ffect of angiogenesis and lymphangiogenesis in HIV-infected PE women. Therefore, this review serves to highlight the effect of pregnancy type and HIV status on angiogenesis and lymphangiogenesis using South African cohorts. We also provide compelling evidence of the mechanism(s) that HIV utilizes to exploit the angiogenic system. Furthermore, we provide data based on highly active anti-retroviral treatment (HAART) on reconstituting the immune system and its influence on PE development.
