Severe haematologic toxicity is rare in high risk HIV-exposed infants receiving combination neonatal prophylaxis

Objectives Combination neonatal prophylaxis (CNP) is recommended in high-risk situations for the prevention of mother-to-child HIV transmission, although data on its safety are limited. The aim of the study was to identify whether neonatal prophylaxis (NP) type is associated with the risk of severe anaemia or neutropaenia. Methods An individual patient data meta-analysis was conducted within six European cohorts, in infants at high risk for acquiring HIV infection. Adjusted logistic regression models were used to assess the risk of National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) grade 3-4 anaemia/neutropaenia at ages 0-6 months. Mixture models of haemoglobin (Hb) level and log(10)-transformed neutrophil count (NC) were used to explore associations with NP type at ages 0-18 months. Results Of 1836 infants, 25% were preterm, 1149 (63%) had antenatal combination antiretroviral therapy (cART) exposure and 395 (22%) received NP (125 received CNP with three drugs). Overall, 117 (6.7%) infants had grade 3-4 anaemia at age 0-6 months and 140 (9.1%) had grade 3-4 neutropaenia. The presence of grade 3-4 anaemia or neutropaenia was not associated with NP type [adjusted odds ratio (aOR) 1.04 for one-drug NP and 1.60 for three-drug NP versus two-drug NP (P = 0.879 and P = 0.277, respectively) for anaemia; aOR 1.33 for one-drug NP and 1.98 for three-drug NP versus two-drug NP (P = 0.330 and P = 0.113, respectively) for neutropaenia], but was associated with preterm delivery. Overall, 7746 Hb and NC results were available for 1836 infants up to age 18 months; no significant differences in predicted Hb level or NC were apparent by NP type. Conclusions A small proportion of infants experienced grade 3-4 haematological adverse events; risk of anaemia or netropenia was not associated with type of NP.