Unexpected CD4 decay, hidden adherence gaps, resilience, and the need for long-acting therapy in a single HIV...

Area of Science:

• Infectious Diseases
• Immunology
• Pharmacology

Background:

• Persistent optimal viral suppression in people living with HIV (PLWH) can mask underlying non-adherence to antiretroviral therapy (ART).
• Significant CD4+ T-cell decay, both absolute and percentage, can occur despite viral suppression, indicating potential adherence issues.
• Understanding hidden non-adherence is crucial for maintaining long-term health outcomes in PLWH.

Purpose of the Study:

• To investigate the prevalence and characteristics of hidden non-adherence to ART in PLWH with unexplained CD4+ T-cell decay.
• To identify reasons for treatment interruptions and their impact on CD4+ T-cell recovery.
• To explore potential strategies for preventing non-adherence and its consequences.

Main Methods:

• Single-center, single-cohort study of HIV-infected individuals.
• Inclusion criteria: persistent optimal viral suppression with >10% CD4+ T-cell decay.
• Data collection: duration of ART interruption, timing of ART resumption before testing, and reasons for non-adherence.

Main Results:

• 15 out of 61 (25%) individuals meeting CD4+ decay criteria admitted to long-lasting ART interruptions (15-28+ days).
• Non-adherent individuals showed significantly worse CD4+ T-cell recovery at 6 months compared to adherent individuals (-0.5 vs +16/mm³).
• Common reasons for ART interruption included travel, psychological issues, poverty, addiction, and relationship problems.

Conclusions:

• Hidden non-adherence to ART is a significant issue in PLWH, even with viral suppression, leading to detrimental CD4+ T-cell count decline.
• Short-term ART resumption before monitoring can mask prolonged treatment gaps, negatively affecting immune reconstitution.
• Long-acting ART formulations and stringent adherence support may be vital in protecting PLWH's health and preventing HIV transmission.