title: Ongoing changes in HIV RNA levels during untreated HIV infection: implications for CD4 cell count depletion.
abstract: BACKGROUND
  Understanding of the interplay between plasma HIV RNA level and CD4 cell count depletion in untreated infection remains incomplete.
  
  
  METHODS
  We studied 1169 people with HIV seen for care at a major London clinic while naive to antiretroviral therapy. We considered pairs (n = 5940) of consecutive simultaneously measured CD4 cell count and plasma HIV RNA values from patients who had never started therapy. Baseline was the first date when both measures were known.
  
  
  RESULTS
  HIV RNA levels increased variably and often substantially from baseline (60% experience an increase of over 50 000 copies/ml by 5 years of follow-up). The current HIV RNA level (i.e. first value of the pair) was strongly associated with the time-standardized change in CD4 cell count, with a mean 106 cells/microl per year greater rate of CD4 cell count decline per log-copy/ml higher current HIV RNA level (P < 0.0001). After adjustment for the current level, higher baseline HIV RNA was not associated with CD4 cell count decline. There was no average CD4 cell count decline with current HIV RNA level below 3.0 log-copies/ml, compared with a 159 cells/microl per year decline for those with HIV RNA at least 5.5 log-copies/ml (P < 0.0001). Further, the current CD4 cell count predicted subsequent changes in HIV RNA level (0.04 log-copies/year greater increases per 100 cells/microl lower CD4 cell count; P < 0.0001).
  
  
  CONCLUSIONS
  The often substantial increases in HIV RNA level observed in untreated HIV infection appear fundamentally linked to CD4 cell count depletion. Research into mechanisms by which HIV RNA levels rise over time should yield insights into the causes of CD4 cell count depletion, as the two processes are intimately linked.
authors.affiliation: HIV Epidemiology & Biostatistics Group, Research Department of Infection and Population Health, Royal Free Campus, UCL (Royal Free Campus), London, UK. andrew.phillips@ucl.ac.uk
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Lampe
authors.forename: Colette J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Geretti
authors.forename: Alison
authors.initials: A
authors.lastname: Rodger
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Lodwick
authors.forename: Valentina
authors.initials: V
authors.lastname: Cambiano
authors.forename: Robert
authors.initials: R
authors.lastname: Tsintas
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008131:London; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load
chemical_list: D012367:RNA, Viral