Predictors of CD4⁺ T-cell counts of HIV type 1-infected persons after virologic failure of all 3 original antiretroviral drug classes

Background. Low CD4⁺ T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4⁺ T-cell counts after triple-class virological failure.Methods. We included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4⁺ T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.Results. The analyses included 2424 individuals with a total of 23 922 CD4⁺ T-cell count measurements. In adjusted models (excluding current viral load and year), CD4⁺ T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/μL [95% confidence interval {CI}, 3.9-41]; P =. 017) or drugs from the new classes (increase, 39 cells/μL [95% CI, 15-62]; P =. 001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log₁₀ copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log₁₀ copies/mL were associated with CD4⁺ T-cell count decreases of 51, 84, 137, and 186 cells/μL, respectively (P <. 001).Conclusions. The approximately linear inverse relationship between log₁₀ viral load and CD4⁺ T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4⁺ T-cell counts and few drug options.