Characteristics, Determinants, and Clinical Relevance of CD4 T Cell Recovery to <500 Cells/ L in HIV Type 1--Infected Individuals Receiving Potent Antiretroviral Therapy

Abstract

Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration.Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load !1000 copies/mL for у5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (у500 cells/mL was defined as a complete response, and !500 cells/mL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses.Results. The median CD4 T cell count increased from 180 cells/mL at baseline to 576 cells/mL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau !500 cells/mL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders ( ). Older age (adjusted P 1 .05 odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count !500 cells/mL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders ( ) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% P ! .001 sensitivity and 72% specificity.Conclusion. Individuals with incomplete CD4 T cell recovery to !500 cells/mL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes.

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

“…1,59 We found that the identical clinical parameters were associated with increased rate of CD4 T-cell recovery by using both approaches and were consistent with other observational studies of CD4 T-cell recovery after cART. 2,16 It is important to note however, that this study was designed to replicate our previous study of Caucasians 22 where we had previously used a survival analysis approach. However, in this study of the UARTO patients, there was a much lower frequency of patients achieving the event (that is, CD4 T-cells 4500cells ml À1 ) as compared with the Caucasians in our prior study 22 (15 versus 80% respectively) and this may have led to over-fitting of the Cox model.…”

“…[1][2][3] These patients remain at increased risk of non-AIDS-related illnesses and mortality despite years of suppressive cART. [4][5][6] Clinical or genetic factors that may predict impaired CD4 T-cell recovery could potentially be used to identify patients who would benefit from earlier initiation of cART.…”

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…[78][79][80][81][82][83] Some suggests that these finding may be linked with higher adherence in older patients, 78,[84][85] but other authors reported a higher risk of inadequate adherence in HIV patients who have other comorbidities and take other medications besides HAART. [86][87] While virological response seems not to be influenced by age, at least biologically, older patients have lower CD4C T-cell gain compared with younger persons, [88][89][90][91][92][93][94][95] even when adjusted for antiretroviral therapy regimens. This is particularly relevant considering that lower CD4 T-cell counts are not only linked to HIV-related opportunistic infections and malignancies, but also lead to higher risk of non-AIDS-related comorbidities, adding to the already elevated risk conferred by age.…”

Italian Consensus Statement on Management of HIV-Infected Individuals with Advanced Disease Naïve to Antiretroviral Therapy

“…High plasma HIV-RNA levels and low CD4+ cell counts, typically found in advanced stages of HIV disease, are both associated with an increased risk of mortality, even after the initiation of combination antiretroviral therapy (cART) [4,5]. In addition, even after cART has been initiated, early viro-immunologic response may be incomplete or slower in patients with more advanced HIV infection at baseline [6,7], and it is also strongly associated with subsequent disease progression [8].…”