Safety of combination antiretroviral prophylaxis in high‐risk HIV‐exposed newborns: a retrospective review of the Canadian experience

Abstract

IntroductionThe optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates.MethodsRetrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling.ResultsNon-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p=0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p=0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age.ConclusionscART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients.

British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018

“…For infants born to ART‐naïve women, or where drug resistance is unlikely, zidovudine, lamivudine and nevirapine is a well‐tolerated combination regimen with the most clinical experience [18,19,21–24] (see Appendix for dosing).…”

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

“…ZDV and didanosine (ddI), drugs that were introduced in the 1990s have only recently shown associations with congenital cardiac defects and cancer, [51,52] respectively, which would not have been apparent without many years of data. Given the changing drugs and changing populations without safety data from clinical trials, ongoing ARV safety surveillance in pregnancy is clearly needed.…”

“…HIV-positive pregnant women who consented to the cohort were prospectively followed during pregnancy, and their infants until age 18. This cohort has yielded important information regarding the safety of ART exposures both prenatally and in the postnatal period, including extensive laboratory and lymphocyte measures in HEU children through 24 months of age [51]. …”

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

“…In a retrospective multicentre Canadian study involving 148 infants at high risk for MTCT receiving CNP using therapeutic doses and 145 infants at low risk receiving ZDV, haematological and growth parameters at birth and at 1 and 6 months of age were evaluated. The authors concluded that CNP was generally well tolerated, but reported that 10.2% of the CNP group had potential treatment‐related adverse effects (nonspecific signs and symptoms, including rash, vomiting, diarrhoea and irritability) versus none of the ZDV monotherapy recipients; furthermore, treatment was discontinued more frequently in the CNP group.…”