The peer-reviewed study, published by Nature Medicine, assessed 284 children from KwaZulu-Natal in whom anti-HIV therapy was initiated at birth following in utero HIV transmission. Vertical transmission to male fetuses was 50% less common than to females. Affected males 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 (i.e. maintained undetectable levels of HIV in the blood even without therapy).
The study’s findings indicate that the reason for these different outcomes between males and females is two-fold: first, female fetuses, 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. Second, the female fetus shares with her mother the same type of innate immune response. Therefore, the female fetus is particularly susceptible to the viruses that have evaded maternal immunity. The male fetus, by contrast, is relatively resistant to these viruses in the mother. The consequence is that, even when transmission does arise in male fetuses, infection may not be sustained.
Professor Philip Goulder, Professor of Immunology at the Department of Paediatrics in Oxford, 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. Nomonde Bengu, a 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.’
Dr. Gabriela Cromhout, a lead researcher on the study at the South African University, 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.’
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.