Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study.
OBJECTIVE
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/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL).


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.
Gilson
R J C
RJ
Centre for Sexual Health and HIV Research, Research Department of Infection & Population Health, University College London, The Mortimer Market Centre, Camden Primary Care Trust, London, UK. rgilson@gum.ucl.ac.uk
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Copas
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Porter
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Gazzard
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D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D019562:Viral Load
D019380:Anti-HIV Agents