Around half of children exposed to antiretrovirals in the womb and just after birth develop clinically significant anaemia and loss of white blood cells (neutropenia), according to German researchers writing in the May 1st edition of Journal of Acquired Immune Deficiency Syndrome.
Although the use of effective HIV therapy has cut the HIV transmission rates from mother to baby to less than two per cent there has been growing concern about drug toxicity in infants exposed to antiretrovirals.
This study involved 221 infants born to HIV-infected mothers taking HIV therapy - either AZT alone or with another NRTI; or a potent antiretroviral combination.
The antiretroviral regimen given to the infants straight after birth was slightly different in this study than in many others. Instead of the more usual six-week course of oral AZT, babies were given a ten day intravenous (IV) course of the drug. This short IV course was preferred because of concerns that the oral drug might not be absorbed from infants’ gastro-intestinal tract, say the researchers.
Blood counts were studied at birth then at two, four, six and twelve weeks. Clinically relevant anaemia was classed as grade 2 or above as defined by a paediatric toxicity scale.
During follow up 119 (54%) infants had grade 2 anaemia or higher on at least one occasion. For 16 of them (7%) the anaemia was bad enough to warrant a red blood cell infusion. The anaemia tended to be worse in those children exposed to potent HIV therapy in the womb rather than zidovudine with or without an NRTI.
Around 40% of the newborns had grade 2 neutropenia at birth. But neutropenia grade 2 or higher occurred in 106 (48%) of infants at least once and eight babies had staphylococcal infections with two of the infections being severe.
The researchers then attempted to adjust for possible confounding factors such as prematurity, birth weight and ethnicity and found that potent anti-HIV therapy exposure in the womb more than doubled the risk of anaemia (odds ratio 2.22, p=0.034) and neutropenia (OR 2.15, p = 0.045).
They also did platelet counts, as other studies had suggested platelet numbers dropped in babies exposed to antiretrovirals.
In fact they found an unexpectedly high proportion of infants had raised platelet counts- with 60% having over 500 platelets/ml on at least one occasion. However there were no complications associated with this thrombocytosis.
The researchers conclude by saying that, although there is no doubt the benefits of antiretrovirals during pregnancy outweigh the risks, all infants need to be closely monitored for signs of toxicity in the weeks after birth. These children also need to be followed-up to study any potential long-term side-effects.
Feiterna-Sperling C et al. Hematologic effects of maternal antiretroviral therapy and transmission prophylaxis in HIV-1- exposed uninfected newborn infants. J Acquir Immune Defic Syndr 45: 43-51, 2007.