title: Poor CD4 recovery and risk of subsequent progression to AIDS or death despite viral suppression in a South African cohort.
abstract: BACKGROUND
  The prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear.
  
  
  METHODS
  This was a cohort study of HIV-positive adults initiating antiretroviral therapy (ART) between April 2004 and August 2007 who achieved viral suppression (<400 copies/ml) by six months on treatment in South Africa. Immunological response at six months was defined as: (1) absolute CD4 reached (<200 vs. ≥ 200 cells/ml); (2) absolute CD4 reached (0-49, 50-200 and ≥ 200 cells/ml); and (3) CD4 increase from ART initiation (<0, 0-49, 50-199 and ≥ 200 cells/ml). We used Cox regression models to determine the relationship between each definition and both new AIDS-defining condition and death.
  
  
  RESULTS
  A total of 4129 patients were eligible for analysis; 212 (5.1%) of those patients experienced a new AIDS-defining condition and 154 (3.7%) died. Smaller CD4 gains by six months were associated with higher hazards of progression to AIDS (CD4<50 vs. ≥ 200 cells/ml; adjusted hazard ratio (aHR): 2.6; 95% CI: 1.2-2.1) and death (aHR: 2.8; 95% CI: 1.4-5.7). A decrease in CD4 count since ART initiation through six months (aHR: 2.4; 95% CI: 1.2-4.9) and smaller CD4 count gains (0-49 cells/ml; aHR: 2.0; 95% CI: 1.2-3.4 and 50-199 cells/ml; aHR: 1.5; 95% CI: 0.9-2.2) were also associated with greater risk of progression to AIDS compared to an increase of ≥ 200 cells/ml. When we examined mortality differences by gender among this virally suppressed cohort, a higher proportion of males died compared to females, 4.7% versus 3.2%, p=0.01. However, in multivariable analysis, we did not observe any significant differences: aHR: 1.39; 95% CI: 0.98-1.95.
  
  
  CONCLUSIONS
  Patients on ART with poor CD4 recovery early in treatment are at greater risk of progression to new AIDS diagnosis or death despite viral suppression. Approaches to managing this sub-group of patients need further investigation.
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; simbat@nicd.ac.za.
authors.forename: Simbarashe
authors.initials: S
authors.lastname: Takuva
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Mhairi
authors.initials: M
authors.lastname: Maskew
authors.affiliation: Center for Global Health and Development, Boston University, Boston, MA, USA.
authors.forename: Alana T
authors.initials: AT
authors.lastname: Brennan
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Long
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Right to Care, Johannesburg, South Africa.
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Center for Global Health and Development, Boston University, Boston, MA, USA; Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Fox
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000706:statistics & numerical data; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D054334:Viral Regulatory and Accessory Proteins / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D054334:Viral Regulatory and Accessory Proteins
keywords: AIDS; CD4 cell count; antiretroviral therapy; discordance; disease progression; immunologic response; viral suppression