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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
Rapid CD4+ cell decrease after transient cART initiated during primary HIV infection (ANRS PRIMO and SEROCO cohorts)
Remonie Seng1, Cécile Goujard, Loïc Desquilbet
1INSERM U822, Le Kremlin-Bicêtre, France.
Insights
A limited course of combination antiretroviral therapy (cART) initiated during primary HIV infection (PHI) may not benefit patients long-term, as CD4 cell counts declined similarly to untreated individuals after treatment cessation.
Area of Science:
- Immunology
- Virology
- Clinical Medicine
Background:
- Primary HIV infection (PHI) is a critical window for intervention.
- Combination antiretroviral therapy (cART) aims to control HIV replication and preserve immune function.
- Understanding the long-term impact of cART initiated during PHI is crucial for treatment guidelines.
Purpose of the Study:
- To model CD4 cell count decline after stopping cART in patients who started treatment during PHI.
- To identify factors influencing CD4 cell count kinetics post-cART cessation.
- To compare CD4 cell count trajectories between treated and never-treated HIV cohorts.
Main Methods:
- Mixed-effects modeling was used to analyze CD4 count kinetics on the square root scale.
- Data from 170 patients in the PRIMO cohort (cART during PHI) and 123 in the SEROCO cohort (never-treated) were analyzed.
- CD4 cell counts were tracked over time after cART interruption or infection diagnosis.
Main Results:
- After cART interruption in the PHI cohort, CD4 counts rapidly declined initially, then slowed.
- Higher CD4 count increases during cART predicted steeper declines post-cessation.
- Three years after cART interruption, mean CD4 loss was 383 cells/microL, compared to 239 cells/microL in never-treated individuals.
Conclusions:
- Limited courses of cART initiated within 3 months of PHI diagnosis may offer no significant long-term advantage in CD4 cell count preservation.
- These findings challenge the established benefit of early, short-term cART initiation in PHI.
- Further research is needed to optimize HIV treatment strategies during primary infection.
Objective:
To modelize the rate of CD4 cell count decline and its determinants after cessation of combination antiretroviral therapy (cART) started during primary HIV infection (PHI) and compare it with never-treated patients.
Methods:
Kinetics of CD4 counts were analyzed on the square root scale by using a mixed-effects model in 170 patients who received cART during PHI from the Primary Infection (PRIMO) cohort and 123 never-treated patients from the Seroconverters (SEROCO) cohort.
Results:
After cART interruption in the PRIMO cohort, the CD4 cell count fell rapidly during the first 5 months and more slowly thereafter. The timing of treatment initiation had no influence on the rate of CD4 cell decline. In contrast, a larger increase in CD4 cell counts during cART was associated with a steeper decline and a larger loss of CD4 cells after treatment interruption. The mean CD4 cell loss 3 years postinterruption was 383 cells per microliter. In the SEROCO cohort, the CD4 T-cell decline was less steep (3-year CD4 loss 239 cells/microL). As a result, the mean CD4 cell counts were similar (416 cells/microL) 3 years after cART interruption (PRIMO) or after infection (SEROCO).
Conclusions:
These data question the benefit of a limited course of cART even when initiated within 3 months after PHI diagnosis.
