Ongoing changes in HIV RNA levels during untreated HIV infection: Implications for CD4 cell count depletion

Andrew N. Phillips, Fiona C. Lampe, Colette J. Smith, Anna Maria Geretti, Alison Rodger, Rebecca K. Lodwick, Valentina Cambiano, Robert Tsintas, Margaret A. Johnson

Research output: Contribution to journalArticlepeer-review


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/μl 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/μl 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/μl lower CD4 cell count; P < 0.0001).

Conclusion: 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.

Original languageEnglish
Pages (from-to)1561-1567
Number of pages7
Issue number10
Publication statusPublished - 19 Jun 2010


  • CD4 cell count
  • HIV
  • immunodeficiency
  • natural history
  • pathogenesis
  • set point
  • viral load


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