Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries

Abstract

Background: Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common.

Methods: Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12-24 months after delivery (n = 1070). Women with a CD4 count of 200-500 cells/mm(3) and gestational age 28-36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: <200 cells/mm(3) initiated antiretroviral therapy, and >500 cells/mm(3) received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin < 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models.

Results: At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥ 6 months) and shorter ARV exposure. Severe anaemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1-2 months of ARV's, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort.

Conclusions: Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring.

Trial registration number: ISRCTN71468401.

Figure 1

Median change (with 95% confidence intervals) in Hb level in the months before and after delivery (t = 0) by intervention arm.

Figure 2

Kaplan-Meier failure curve showing anaemia failure (Hb <8.0 g/dL) by intervention arm, with onset of risk at enrolment (Figure2A) and at delivery (Figure2B), censored at 18 months follow-up.

Figure 3

Kaplan-Meier failure curve showing anaemia failure (Hb < 8.0 g/dL) in RCT intervention arms, stratified by enrolment Hb level.

Figure 4

Incidence of severe anaemia (including 95% confidence intervals) by ARV duration for all study arms (includes delivery related failures occurring at median t = 1.15 months following treatment initiation) ( P- value comparing incidence in <1 versus 1–1.9 month duration = 0.004).