Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study^*

Abstract

Objectives Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time‐points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. Methods Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment‐naïve patients starting HAART with HIV viral load (VL)>1000 HIV‐1 RNA copies/mL at baseline and <50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6–10 (midpoint 8) months or 10–14 (midpoint 12) months as having a discordant (CD4 count increase <100 cells/μL from baseline) or concordant response (CD4 count increase ≥100 cells/μL). Results Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73–6.47, P<0.001] than at 8 months (IRR 2.08, 95% CI 1.19–3.64, P=0.010), but not with new AIDS events. Conclusions Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of ‘slow’ responders. Management strategies to improve outcomes for discordant responders need to be investigated.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

“…In contrast, patients with a complete immunological response (i.e. a CD4 + T cell count above 500 cells/ mm 3 ) might present with the same mortality rate as the general population [6,7]. The mechanisms sustaining this inadequate immune recovery in patients with virological success remain elusive.…”

“…Importantly, this incomplete immune recovery, also called inadequate immunological response [4] (iIR), is associated with increased morbidity and mortality [2,3,[5][6][7]. In contrast, patients with a complete immunological response (i.e.…”

“…It has been repeatedly described that approximately 5-30% of highly active anti-retroviral therapy (HAART)-treated patients fail to significantly improve their CD4 + T cell numbers upon effective therapy after obtaining virological success [1][2][3]. Importantly, this incomplete immune recovery, also called inadequate immunological response [4] (iIR), is associated with increased morbidity and mortality [2,3,[5][6][7].…”

EVOLUTION OF PATIENTS WITH AIDS AFTER cART: CLINICAL AND LABORATORY EVOLUTION OF PATIENTS WITH AIDS AFTER 48 WEEKS OF ANTIRETROVIRAL TREATMENT

“…Not all patients under cART exhibit a rise in CD4 + T cell counts despite viral suppression 11,12,38,39 . This observation has been assigned to factors related to pre-therapy CD4 + T counts and VL, age at treatment initiation and time to reach viral suppression after the start of therapy.…”

Temporal trends in CD4-positive T-cell counts among AIDS patients in Tianjin, China: 2005–2016

“…Immunological suppression and disturbances caused by HIV infection contribute to the decline in CD4 cell counts and predict both morbidity and mortality from AIDS [35,36]. Moreover, a majority of studies have shown evidence for an increased risk for progression to AIDS or death among those with low CD4 cell counts [37][38][39][40][41][42][43].…”