Anaemia in Pregnancy Is Associated with Advanced HIV Disease

Citation: Nandlal V, Moodley D, Grobler A, Bagratee J, Maharaj NR, et al. ( Anaemia in Pregnancy Is Associated with Advanced HIV Disease Vikesh Nandlal 0 Dhayendre Moodley 0 Anneke Grobler 0 Jayanthilall Bagratee 0 Niren R. Maharaj 0 Paul Richardson 0 Claire Thorne, UCL Institute of Child Health, University College London, United Kingdom 0 1 Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of KwaZulu Natal , Durban , South Africa , 2 Department of Pathology, Johns Hopkins University School of Medicine , Baltimore , Maryland, United States of America, 3 Center for the AIDS Programme of Research in South Africa-CAPRISA , Durban , South Africa Background: Anaemia is a common clinical finding in HIV infected women and has been associated with advanced disease. The use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia. We report the prevalence, type, severity and incidence of anaemia in a cohort of HIV infected women who initiated antiretroviral prophylaxis or treatment during pregnancy. Methods and Materials: This is a retrospective cohort data analysis of 408 HIV infected pregnant women who participated in a breastfeeding intervention study (HPTN 046 Study, ClinicalTrials.gov NCT 00074412) in South Africa. Women initiated zidovudine prophylaxis for PMTCT or triple antiretroviral treatment in pregnancy according to the standard of care. Laboratory and clinical data in pregnancy, ,72 hours and 2 weeks postdelivery were extracted from the main database and analysed. Results: The mean Hb concentration was 10.6 g/dL at baseline and 262/408 (64.2%) women were diagnosed with anaemia (Hb,11 g/dL) in pregnancy, 48/146 (32.9%) subsequently developed anaemia intrapartum or postpartum and 89/310 (28.7%) of all cases of anaemia remained unresolved by 2 weeks postdelivery. In a univariate analysis, CD4 count and gravidity were significant risk factors for anaemia in pregnancy, RR 1.41; 1.23-1.61 (p,0.001) and 1.10; 1.01-1.18 (p = 0.02) respectively. After adjusting for antiretroviral regimen, age and gravidity in a multivariable analysis, only the CD4 count remains a significant risk factor for anaemia in pregnancy and postdelivery. Conclusion: In conclusion, anaemia was most common among women in the advanced stage of HIV infection (CD4,200 cells/mm3). There was no evidence of an association between ZDV or triple ARVs and anaemia. - Funding: No funding was obtained for the sub study. The HPTN 046 study was funded by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group 5U01AI069469) which receives funding from the US National Institute of Health (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. The World Health Organization estimates that nearly half of all women in low resource countries have anaemia (52%) [1]. Women of reproductive age (1549 years) are most commonly affected and likely due to excessive blood loss during menstruation, insufficient dietary intake, parasitic infections and increased physiological demand during pregnancy [2]. In pregnancy, iron deficiency anaemia is associated with poor birth outcomes such as increased risk of still births, low birth weight infants, intrauterine growth restriction and neonatal sepsis [3,4]. More recently, anaemia was also a common clinical finding in HIV infected women and has been associated with advanced disease. In Sub-Saharan Africa, a region most affected by the HIV pandemic, anaemia in HIV infected women has been independently associated with adverse maternal and fetal outcomes in pregnancy [57]. In 2012, the Saving Mothers Report in South Africa concluded that HIV infection (70%) and anaemia (30%) were the commonest conditions among women who died during pregnancy or in the puerperium [8]. Although not explored in the Saving Mothers Report, through other studies the use of antiretroviral drugs such as Zidovudine (ZDV) either for prevention of mother to child transmission (MTCT) of HIV or used in combination with other antiretrovirals have been implicated in the development or increased severity of anaemia [9]. A recent clinical trial across three Sub-Saharan African countries demonstrated that women randomized to short or longer ZDV containing regimens were at similar risk of severe anaemia and the longer the duration of a triple antiretroviral (ARV) regimen the greater the reduction in the incidence of anaemia [10]. These findings are inconsistent with studies conducted in Malawi and Mozambique that implicated ZDV containing regimens as risk for anaemia [11]. Zidovudine containing regimens as prophylaxis for PMTCT remains the most affordable and cost-effective option in most SubSaharan African countries with a high HIV disease burden. Yet, not many studies have sought to confirm if anaemia, a potential side effect of Zidovudine use, could be attributed to the HIV disease stage itself and could be avoided if pregnant women in the advanced stage of disease are treated with a triple antiretroviral regimen. We report the prevalence, type, severity and subsequent incidence of anaemia in a cohort of HIV infected women during pregnancy, within 72 hours post-delivery and 2 weeks postdelivery in association with HIV disease stage (CD4 count) alone or in relation to ARV prophylaxis or treatment. HIV positive pregnant women in South Africa during the course of the HPTN046 study were eligible for triple ARV (D4T/3TC/NVP) if they were in the advanced stage of the disease (CD4,200) and ZDV used as prophylaxis to prevent MTCT in women not meeting the treatment criteria. We also describe the potential impact of anaemia on maternal and infant birth outcomes. Ethics Statement This secondary data analysis study was reviewed and approved by the Institutional Review Board of University of KwaZulu Natal. Participant informed consent specific to this sub study was not obtained; hence participant records were anonymized and deidentified prior to analysis. This study is a retrospective cohort data analysis of motherinfant pairs who participated in the HPTN 046 Study (Clinical Trials.gov. Identifier: NCT 00074412) conducted in Umlazi, South Africa [12]. The HPTN046 Study was a Phase III randomized controlled trial conducted in South Africa, Uganda, Zimbabwe and Tanzania to determine the efficacy and safety of an extended regimen of nevirapine in infants born to HIV-infected women to prevent transmission of HIV through breastfeeding. Further details of the study conduct and outcome measures have previously been published and can also be accessed at www. HPTN.org. Data for the South African cohort prior to randomisation i (...truncated)