Viral Load Increase and CD4 Cell Loss Closely Linked in Untreated People with HIV

Higher viral load was associated with greater CD4 cell decline among HIV positive people not on antiretroviral therapy, according to a report in the June 19, 2010 issue of AIDS. Individuals with HIV RNA levels less than 1000 copies/mL did not experience appreciable annual decreases in CD4 count, while those with viral loads of about 300,000 copies/mL or more lost an average of 159 cells/mm3 per year.

Andrew Phillips from Royal Free Hospital and colleagues looked at the relationship between viral load and CD4 cell depletion in 1169 HIV positive people treated at their large clinic in London who had not yet started antiretroviral treatment.

The researchers analyzed 5940 pairs of simultaneous CD4 cell and HIV RNA measurements, which were done every 3 months on average.

Results

·      The overall average annual CD4 cell decline was 66 cells/mm3 and HIV viral load increased by about 25% per year on average.

·      Viral load increases varied widely among individual participants, however, with many experiencing "substantial" increases from baseline (the first measurement).

·      60% of patients saw an increase of more than 50,000 copies/mL by 5 years of follow-up.

·      Current viral load level was strongly correlated with time-standardized changes in CD4 count.

·      Each additional HIV RNA increase of 1 log copies was associated with an average extra CD4 cell loss of 106 cells/mm per year.

·      After adjusting for current level, however, higher baseline viral load was no longer associated with CD4 cell declines.

·      Participants with a current HIV RNA level below 3.0 log (about 1000) copies/mL showed no decrease in CD4 cells, on average.

·      In contrast, patients with HIV RNA levels of at least 5.5 log (about 316,000) copies/mL lost an average of 159 cells/mm3.

·      Conversely, current CD4 cell count predicted subsequent changes in viral load, with each 100 cells/mm3 decrement associated with an average 0.04 log (about 3) copies/mL increase in HIV RNA.

·      Almost all participants with a low CD4 count below 200 cells/mm3 had at one time had a viral load above 4.0 log (about 10,000) copies/mL.

Based on these findings, the researchers concluded, "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," they added.

Investigator affiliation: HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Royal Free Campus, London, UK.

7/6/10

Reference

AN Phillips, FC Lampe, CJ Smith, and others. Ongoing changes in HIV RNA levels during untreated HIV infection: implications for CD4 cell count depletion. AIDS 24(10): 1561-1567. June 19, 2010.