Editor's Note: At the 25th International AIDS Conference (AIDS 2024) in Munich, Germany, a study on the impact of HIV on the gut virome of children garnered significant attention. This research was conducted by scientists from the University of Washington in Seattle, Seattle Children's Hospital, and the University of Cape Town in South Africa. The study revealed unique changes in the gut virome of HIV-exposed uninfected (HEU) infants born to HIV-infected mothers.

The study was designed to explore the effects of HIV infection on the establishment of the infant gut virome and its relationship with bacterial microbiota and vaccine responses. The research team recruited 40 pairs of HIV-infected mothers and their HIV-uninfected infants from South Africa as the case group, and 40 pairs of HIV-uninfected mothers and their infants as the control group. Fecal samples from these infants were collected from birth to 36 weeks and subjected to metagenomic sequencing of viral DNA and RNA. Additionally, the researchers analyzed viral and bacterial communities in the mothers’ breast milk and the infants’ feces.

Using advanced metagenomic sequencing technology, the study comprehensively analyzed viral DNA and RNA from purified viral particles. Multiparameter flow cytometry was employed to measure vaccine responses, and 16S rRNA gene sequencing was used to profile bacterial communities. These integrated methods allowed the researchers to detail the specific impacts of HIV infection on the infant gut virome and bacterial microbiota.

The study found that compared to infants not exposed to HIV, HEU infants exhibited significantly different gut virome characteristics within the first week of life. Specifically, the relative abundance of Bifidobacterium phages in HEU infants’ feces increased 11-fold (P<0.001), while the abundance of Bifidobacterium decreased 24-fold (P<0.001). Further analysis showed a significant positive correlation between the abundance of Bifidobacterium longum in the first week and the later response to Bacillus Calmette-Guérin (BCG) vaccination (R2=0.35, P=0.002). Conversely, the abundance of another eukaryotic DNA virus, Smacoviridae, in the first week was significantly negatively correlated with the BCG response (R2=0.12, P=0.04). Moreover, the study found that the HIV status of the mother was significantly associated with the composition of her breast milk (F=3.28, P<0.001) and the infant’s gut virome (F=1.93, P=0.004).

This research reveals the unique challenges faced by HEU infants in establishing their gut virome, which may be linked to higher morbidity and mortality rates, weakened vaccine responses, and changes in gut bacterial microbiota. Understanding these changes can aid in developing targeted interventions to improve the health outcomes of HEU infants.

Additionally, the study underscores the profound impact of maternal HIV status on the early development of the infant gut microbiome, providing new insights into the risk factors of vertical HIV transmission. Further research may explore how modulating the gut microbiota can mitigate the adverse health effects of HIV infection in infants.

This study highlights the need to consider the long-term impacts of HIV infection on the gut microbiota and overall health of related populations in HIV prevention efforts. Through multidisciplinary collaboration and the implementation of comprehensive intervention measures, we can provide more holistic and effective healthcare and support to HIV-infected individuals and their families.

Original Article: “HIV infection alters the breastmilk virome of mothers living with HIV and the gut virome of related infants through early life.” AIDS 2024 OAA0606LB