Abstract
Background: The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+. Methods: We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+ <200 cells/mm3. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4+ during the study. Results: CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value < 0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR) = 1.22; q-value = 0.011), increase in CD4+ ≥P75th [adjusted odds ratio (aOR) = 2.31; q-value = 0.005], slope of CD4+ recovery (aAMR = 1.25; q-value = 0.008), slope of CD4+ recovery ≥ P75th (aOR = 2.55; q-value = 0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR = 1.89; q-value = 0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR = 1.43; q-value = 0.031), increase in CD4+ ≥P75th (aOR = 3.92; q-value = 0.030), slope of CD4+ recovery (aAMR = 1.40; q-value = 0.036), slope of CD4+ recovery ≥ P75th (aOR = 3.42; q-value = 0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR = 5.68; q-value = 0.015). Conclusion: In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started cART with low CD4+ T-cell counts.
Highlights
Combination antiretroviral therapy tends to achieve undetectable plasma viral load levels in the vast majority of the human immunodeficiency virus (HIV)-infected patients treated
D-binding protein (DBP) rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio 1.22; q-value 0.011), increase in CD4+ ≥P75th [adjusted odds ratio 2.31; q-value 0.005], slope of CD4+ recovery, slope of CD4+ recovery ≥ P75th and achievement of CD4+ ≥500 cells/mm3
In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started Combination antiretroviral therapy (cART) with low CD4+ T-cell counts
Summary
Combination antiretroviral therapy (cART) tends to achieve undetectable plasma viral load levels in the vast majority of the human immunodeficiency virus (HIV)-infected patients treated. The causes of this lack of CD4+ recovery among cART-treated patients are not well known, but it appears to be a complex and multifactorial phenomenon (Yang et al, 2020) In this regard, many factors involved in CD4+ recovery have been described, among which include age, low CD4+ T-cells nadir, severe immunodeficiency at the time of cART initiation, low baseline CD4/CD8 ratio, immune exhaustion, abnormal immune activation, reduced output in the bone marrow and thymic, increased senescence and apoptosis of T-cells, lymphoid tissue fibrosis, imbalance in Treg and Th17 cells, microbial translocation, persistent HIV replication, and host genetic background, among others (Yang et al, 2020). We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+
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