‘Baby boys more likely to achieve HIV cure than girls’
A GROUNDBREAKING study published in the prestigious peer-reviewed journal Nature Medicine last week showed that baby boys were more likely to achieve HIV cure/remission than baby girls.
The study included scientists from the universities of KwaZulu-Natal (UKZN) and Oxford, the Africa Health Research Institute (AHRI) at UKZN, as well as the Ragon Institute of Mass General and Massachusetts Institute of Technology Harvard, in the US.
The observational study took place between 2015 and 2023 and included 284 mother-child pairs living with HIV in KwaZulu-Natal, the epicentre of HIV prevalence globally.
The study assessed 284 children from the province for whom anti-HIV therapy was initiated at birth following in-utero HIV transmission. Sixty percent of the group were girls. Vertical transmission to baby boy foetuses was 50% less common than to girls.
Affected boys had lower levels of the virus in the blood, and to date in this study, four male infants have been identified who have achieved HIV cure/remission (that is, maintained undetectable levels of HIV in the blood even without therapy).
The reason for these different outcomes between boys and girls is twofold: first, studies have indicated that female foetuses, like their adult counterparts, typically make stronger immune responses than males, according to the study. However, an overly active immune response can increase susceptibility to infections such as HIV.
Second, the female foetus shares with her mother the same type of innate immune response. Therefore, the female foetus is particularly susceptible to the viruses that have evaded maternal immunity.
The male foetus, by contrast, is relatively resistant to these viruses in the mother. The consequence is that, even when transmission does arise in male foetuses, infection may not be sustained.
An interesting observation of the study indicated that in five sex-discordant twin sets in the cohort, HIV was only acquired in the girl twin. This is further evidence that in-utero transmission of HIV is higher in female foetuses due to the higher levels of immune activation, both antenatally and postnatally, making female foetuses more susceptible to infection in the first two years of life.
Dr Nomonde Bengu, a clinician and lead researcher on the study at Queen Nandi Regional Hospital in KwaZulu-Natal, said: “This is a breakthrough result in South Africa, where almost 8 million people are living with HIV.
“This will transform the way that people here view HIV and will provide much-needed hope for the future.”
Professor Philip Goulder, professor of immunology at the Department of Paediatrics in Oxford and a faculty member at AHRI and lead researcher on the study, said: “These results are exciting because, first of all, HIV cure/ remission is very rare and this study highlights the fact that it, nonetheless, is achievable.
“Furthermore, we have identified some of the key mechanisms by which HIV cure/remission can be achieved, and this is relevant to cure strategies not only aimed at children but those targeting all 39 million people living with HIV.”
Dr Gabriela Cromhout, a lead researcher on the study from UKZN, said: “While this study is highly encouraging in showing that cure/ remission can happen in a small subset of children, especially in male children, following very early initiation of therapy, it is clear that other interventions are also necessary, such as broadly neutralising antibody therapy and T-cell vaccines, in order to make the size of impact that is urgently needed in the cure field. Our team is excited to be part of taking this field forward.”
The study, titled “Sustained aviraemia despite antiretroviral therapy non-adherence in male children following in-utero HIV transmission”, was supported by the Wellcome Trust, the National Institutes of Health as well as the Penta Foundation.