Strong sex bias in elite control of paediatric HIV infection

Abstract

Background:Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection.Methods:We describe 11 ART-naive elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe.Results:All but one of the elite controllers (91%) are females. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age of 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4+ cell counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5–10-fold lower than in adults.Conclusion:Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females.

Early antiretroviral therapy-treated perinatally HIV-infected seronegative children demonstrate distinct long-term persistence of HIV-specific T-cell and B-cell memory

“…It is also important to mention that, albeit not statistically significant, all but one of the seronegative patients are female patients. According to this data, and a recently published work [28] where 10 out of 11 posttreatment controllers were girls, we believe that sex may play a role in the ability to control HIV in early treated perinatally HIV-infected children. This aspect should be further investigated in larger studies.…”

Clinical Features of HIV Arthropathy in Children: A Case Series and Literature Review

“…Women are over-represented amongst HIV-infected individuals with the capacity to spontaneously suppress viraemia without ART, known as elite controllers. Across the literature, approximately 80% of adult elite controllers and 90% of paediatric elite controllers are female (71,(75)(76)(77)(78). Sex differences in other non-communicable HIVassociated comorbidities, such as cardiovascular disease, neurocognitive disorders and malignancies, have been linked to substantial differences in immune activation and regulation between males and females living with HIV (79)(80)(81).…”

“…By comparison, the median survival time in untreated adults is approximately 10 years (86). It is therefore surprising that a significant proportion of children (5-10%) exhibit the immunological phenomenon of non-progression, which is extremely uncommon in adults (75,87). Non-progressors are ART-naïve HIV-infected individuals who do not experience immunosuppression but maintain normal CD4+ counts despite ongoing viraemia (75,88).…”

Learning From the Exceptions: HIV Remission in Post-treatment Controllers

“…The majority of PTCs identified were male, likely reflecting the sex distribution of the clinical trial participants (6, 7, 9, 11, 12, 15–18). Intriguingly, there have been reports that female gender may be associated with a higher chance of post-treatment HIV control (10) and spontaneous control (33, 34), highlighting the need for studies focusing on female participants of treatment interruption trials. In addition, the majority of PTCs have been reported by studies from North America and Europe (6, 7, 9–12, 15–18) and little is known about PTCs from outside of those regions.…”