Predictors of immunological non-response despite virological suppression in people living with HIV on antiretroviral therapy: A systematic review and meta-analysis.
Brian Eka Rachman, Yehuda Tri Nugroho Supranoto, Fitri Revita Nurannisa et al.
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In 30 seconds
This systematic review and meta-analysis examined clinical, demographic and molecular predictors of inadequate CD4+ T-cell recovery despite viral suppression on antiretroviral therapy in people living with HIV. It included 59 studies and 19,511 individuals with immunological non-response. Significant associations included male sex, older age, coinfections, tuberculosis, advanced HIV stage and lower baseline or nadir CD4+ counts. Advanced HIV stage had the largest reported clinical association: OR 2.66 (2.34-3.02). The review also identified 57 biomarkers as potential predictors, implicating multiple immunological pathways.
Key findings
- Male sex was associated with immunological non-response: OR 1.33 (1.12-1.58).
- Older age was associated with non-response, with a mean difference of 2.61 (1.42-3.81).
- Advanced HIV stage had an OR of 2.66 (2.34-3.02); tuberculosis had an OR of 1.77 (1.41-2.21).
- Lower baseline and nadir CD4+ counts were associated with non-response: SMD -3.82 (-4.94-(-2.70)) and SMD -1.69 (-2.69-(-0.68)), respectively.
Why it matters
Incomplete CD4+ recovery can persist despite effective viral suppression, and this synthesis indicates that it is associated with a range of clinical and demographic factors as well as potential biomarkers. Recognising this multifactorial pattern may help frame assessment of immune recovery and inform research into approaches tailored to the characteristics of ART-treated individuals.
What to keep in mind
The review combines studies with differing designs and populations; the abstract does not report the extent of heterogeneity or the quality ratings of the included studies.