HIV-1 reservoir evolution in infants infected with clade C from Mozambique. (February 2023)

• Record Type: Journal Article
• Authors: Koofhethile, Catherine K.; Rinaldi, Stefano; Rassadkina, Yelizaveta; Dinh, Vinh B.; Gao, Ce; Pallikkuth, Suresh; Garcia-Broncano, Pilar; de Armas, Lesley R.; Pahwa, Rajendra; Cotugno, Nicola; Vaz, Paula; Lain, Maria Grazia; Palma, Paolo; Yu, Xu G.; Shapiro, Roger; Pahwa, Savita; Lichterfeld, Mathias
• Is Part Of: International journal of infectious diseases. Volume 127(2023)
• Page Start: 129
• Page End: 136
• Publication Date: 2023-02
• Subjects: Reservoir -- Evolution -- Infants -- HIV-1 -- Integration sites; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2022.11.042
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: Intact HIV-1 proviruses decline rapidly after antiretroviral treatment initiation in infants. Clonal expansion of intact proviruses can occur during early-stage antiretroviral treatment. Viral rebound may be linked to intact proviruses integrated into genes. Activating the chromatin marks proximal to the intact proviruses may promote viral rebound. Abstract: Background: The persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants. Methods: Here, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing. Results: We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harboring intact proviruses and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated into genic and accessible chromatin locations. Conclusion: Together, these results permit rare insight into the evolution of the HIV-1 reservoir in infants infected with HIV-1 and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution analysis of HIV-1 reservoir cells after early antiretroviral treatment initiation in infants.