Three-Month cART Initiated During Primary HIV Does Not Correct the Structural, Immune, and Microbial Abnormalities...

Area of Science:

• Gastroenterology
• Immunology
• Virology
• Microbiome Research

Background:

• HIV infection severely impacts gut structure, immunity, and microbiome, causing immune activation and inflammation.
• These gut alterations contribute to non-infectious comorbidities in people living with HIV (PLWH).
• The efficacy of combination antiretroviral therapy (cART) initiated during primary HIV infection (PHI) on gastrointestinal health is largely unknown.

Purpose of the Study:

• To investigate the effects of 12-week cART on gastrointestinal structure, immunity, and mucosal microbiome in PLWH with PHI.
• To assess whether early viro-suppressive treatment can reverse HIV-associated gut abnormalities.

Main Methods:

• Eleven participants with PHI underwent colonoscopy with biopsies, peripheral blood mononuclear cell (PBMC), and plasma collection before and after 12 weeks of cART.
• Gut biopsies were analyzed for structural changes (E-cadherin, collagen) and immune cell populations (macrophages, T cells).
• PBMCs and gut tissue microbiome composition were analyzed.

Main Results:

• Despite 12-week cART, gut barrier damage (E-cadherin loss, collagen deposition) progressed in PHI participants.
• CD4+ and γδ T-cell frequencies remained stable, with decreased activation in the colon, but no changes in Th17 and Treg cells.
• Peripheral inflammation and gut barrier integrity markers showed no significant changes; however, the gut microbiome composition evolved.

Conclusions:

• Early initiation of 12-week cART does not correct HIV-mediated gut damage or fully revert the pro-inflammatory signature.
• Continued gut injury despite early treatment suggests a limited efficacy of cART in preventing long-term complications.
• These findings highlight the pathogenetic link between persistent gut injury and the development of non-communicable comorbidities in PLWH.