South African Study Recommends Changing WHO Regulations on PMTCT

The World Health Organization’s (WHO) guidelines on the Prevention from Mother to Child (PMTCT) programme recommends that all HIV exposed uninfected infants (HEU’s) born to HIV positive mothers receive cotrimoxazole (CTX) prophylaxis, commencing at 4–6 weeks of age and continued until HIV infection can be excluded. A recent study by UKZN and the South African Medical Research Council (SAMRC) is set to recommend changing these WHO guidelines resulting in global policy changes in the management of HEU’s.

UKZN’s Emeritus Professor Anna Coustoudis from the Department of Paediatrics and Child Health reflected on her research team’s findings, ‘The results from our study are exciting and will facilitate a change in the WHO and our own country’s guidelines with regards to the treatment of HEU’s. Our study indicates that there is no benefit of daily CTX among HEU breastfed infants, whose mothers are accessing a PMTCT programme and adhering to lifelong Antiretroviral Therapy (ART) in a non-malaria area. We therefore recommend that it is removed from the PMTCT programme in non-malaria countries.’

The study was conducted over a five-year period, between October 2013 and October 2018 at the Lancers Road and Cato Manor clinics in Durban, South Africa. Durban is regarded as the epicenter of the HIV epidemic. A cohort of 1219 HEU’s were enrolled in the study with 611 placed in the arm that received CTX and 608 in the No CTX arm. The study consisted of 653 male and 566 female HEU’s. All of the infants that were enrolled were healthy, breastfeeding infants born to HIV positive mothers (actively in PMTCT follow-up). The infants were HIV negative prior to the 6 week enrollment visit and were followed up until 12 months of age.

Interestingly a sub-study examining the microbiome of infants in the study found that the infants taking CTX prophylaxis had significantly higher resistance gene abundance than infants not taking CTX prophylaxis.  Additionally infants taking CTX had decreased inter-individual microbiome diversity.  These alterations to the microbiome are considered to be unfavourable and may have consequent negative health impacts.

Coutsoudis further stated, ‘The findings of increased resistance to CTX are serious since some evidence exists that CTX resistance also confers with resistance against other important antibiotics used during childhood, for common illnesses.  Since antibiotic resistance is a growing threat, and since these studies have shown CTX prophylaxis increases antibiotic resistance genes while showing no clinical benefit for HEU infants in nonmalaria countries, these data reiterate the call for revising the current cotrimoxazole guidelines for HEU infants when mothers are actively receiving ART.’

‘The other benefits of removing CTX as a routine treatment for HEU’s includes cost savings, a reduction in the adverse health of the infants and a likely increase in quality of life of infants. We believe that CTX prophylaxis should not be started in HEU’s that have a negative HIV test at birth and whose mothers are receiving and adherent to lifelong ART,’ said Coutsoudis.

– UKZN’s Emeritus Professor Anna Coutsoudis