Dynamics in HIV-DNA levels over time in HIV controllers

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• HIV controllers (HIC) maintain low viral loads without treatment but exhibit heterogeneous progression risks.
• Understanding HIV reservoirs is key to elucidating long-term viral control mechanisms in HIC.

Purpose of the Study:

• To explore factors associated with HIV reservoirs and their dynamics in HIC.
• To identify predictors of HIV reservoir changes in individuals with controlled HIV infection.

Main Methods:

• Analysis of HIV-DNA levels in 202 individuals from the ANRS-CODEX cohort with longitudinal data.
• Application of mixed-effect linear models to assess HIV-DNA dynamics over time.
• Multivariate analysis to identify independent markers associated with reservoir changes.

Main Results:

• Median HIV-DNA levels were low, with significant heterogeneity among HIC.
• Lower HIV-DNA was associated with protective HLA-B*27/B*57 alleles, lower HIV-RNA, and reduced immune activation.
• Mathematical modeling revealed decreasing HIV-DNA in 46% and increasing levels in 54% of HIC over a median follow-up of 47.6 months.
• HLA-B*27/B*57 alleles, low baseline HIV-RNA, and low baseline HIV-DNA independently predicted HIV-DNA decrease.

Conclusions:

• A subset of HIC experiences a progressive decline in their HIV reservoir, linked to effective viral control.
• Identifying HIC with decreasing reservoirs can help pinpoint individuals with a low risk of disease progression.
• These findings suggest that some HIC may not require antiretroviral treatment.