Delaying antiretroviral therapy reduces immunologic health

the Clinical Advisor take:

The deferral of antiretroviral therapy beyond 12 months of estimated dates of seroconversion reduces the likelihood of immunologic health in patients with HIV-1, results of a study published in JAMA Internal Medicine indicate.

“In individuals with HIV-1 infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized,” wrote Jason F. Okulicz, MD, of the Infectious Disease Clinical Research Program in Bethesda, Maryland, and colleagues.

To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4 T-cell counts, AIDS risk, and immune function, the investigators conducted an observational study with patients enrolled in the U.S. Military HIV Natural History Survey. The timing of ART was indexed to the estimated dates of seroconversion (EDS) and/or entry into the cohort.

The median CD4 count in populations not infected with HIV-1 was approximately 900 cells/μL. Among the 1,119 patients diagnosed with HIV-1, CD4 normalization was achieved in 38.4% versus 28.3% of those initiating ART within 12 months versus after 12 months from the EDS (P=0.001)

Incrementally higher CD4 recovery (<500, 500 to 899, and ≥900 cells/μL) was associated with stepwise decreases in AIDS risk and reversion of markets of immune activation, dysfunction, and responsiveness to levels approximating those found in patients not infected with HIV-1.

The participants with a CD4 count of 500 cells/μL or higher at study entry (adjusted odds ratio [aOR], 2.00) or ART initiation (aOR, 4.08) had significantly higher CD4 normalization rates compared with other participants.

Even among patients with a CD4 count of 500 cells/μL or higher at both study entry and before ART, the odds of CD4normalization were 80% lower in those initiation ART after 12 months from EDS and study entry (aOR, 0.20). Initiation of ART within 12 months of EDS was associated with a significantly lower risk of AIDS (7.8% versus 15.3%; P=0.002), reduced T-cell activation, and increased responsiveness to hepatitis B vaccine.

Delaying ART reduces immunologic health
Delaying ART reduces immunologic health

Importance  In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized.

Objective  To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4+ T-cell counts, AIDS risk, and immune function.

Design, Setting, and Participants  Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined.

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