HIV Cure Possible in Male Infants

HIV Cure Possible in Male Infants

A ground-breaking, world-first international study published in the prestigious peer-reviewed journal Nature Medicine shows that male infants are more likely to achieve HIV cure/remission than female infants.

The study included scientists from the Universities of KwaZulu-Natal (UKZN) and Oxford, the Africa Health Research Institute (AHRI) at UKZN, the Ragon Institute of Mass General, and the 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 (LWH) in KwaZulu-Natal, South Africa – the global epicentre of HIV prevalence.

The study assessed 284 children among whom anti-HIV therapy was initiated at birth following in utero HIV transmission. Sixty percent of the cohort was female. Vertical transmission to male foetuses was 50% less common than to females. Affected males had lower levels of the virus in the blood and at the time of the study, four male infants had been identified who achieved HIV cure/remission (ie, maintained undetectable levels of HIV in the blood even without therapy).

The reason for these different outcomes between males and females is twofold: firstly, studies have indicated that female foetuses, like their adult counterparts, typically make stronger immune responses than males. However, an overly active immune response can increase susceptibility to infections such as HIV. Secondly, the female foetus shares her mother’s innate immune response. Therefore, the female foetus is particularly susceptible to viruses that have evaded maternal immunity. By contrast, the male foetus is relatively resistant to these viruses in the mother. Consequently, even when transmission does arise in male foetuses, infection may not be sustained.

An interesting observation of the study was that in five sex-discordant twin sets in the cohort, HIV was only acquired in the female 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 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 have the level of impact that is urgently needed in the cure field. Our team is excited to be part of taking this field forward.’

Professor Philip Goulder, Professor of Immunology at the Department of Paediatrics at Oxford University and a faculty member at AHRI, who was the 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 is nonetheless 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 the 39 million people living with HIV.’

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 eight million people are living with HIV. It will transform the way that people here view HIV and will provide much-needed hope for the future.’

The study, entitled Sustained Aviraemia Despite Anti-Retroviral Therapy Non-Adherence in Male Children Following in Utero HIV Transmission, was supported by the Wellcome Trust, the National Institutes of Health and the Penta Foundation.

Words: Philip Goulder and MaryAnn Francis

Photographs: Supplied