Results of a large
observational study underline the importance of closely monitoring viral load
in HIV-positive patients who have yet to start antiretroviral therapy,
especially if they are older. The research is published ahead of print in the
online edition of AIDS. Viral load increased progressively with time, and
increases were especially sharp in older patients. Falls in CD4 cell count were
closely related to current viral load.
“The current viral
load, to a much greater degree than any previous measure, determines the
ongoing rate of CD4 count depletion,” comment the authors. “Age was
significantly associated with the change in viral load. Faster rises were
observed in older people.”
In people who are
antiretroviral naive (have not started HIV treatment), HIV infection usually involves a steady increase in viral
load accompanied by a fall in CD4 cell count. If HIV therapy is not started,
this leads to the development of opportunistic infections and AIDS-related
Routine HIV care
should therefore involve the regular monitoring of CD4 count and viral load.
However, there are ongoing uncertainties about the precise rate of viral load
increase in treatment-naive individuals and the relationship with falls in CD4
count. It is also unclear if co-factors such as age, sex and HIV transmission
category are associated with faster changes in these key prognostic markers.
understanding of these important questions is needed to better inform decisions
about the best time to start HIV treatment. Investigators from a collaboration of
36 European cohort studies (COHERE) therefore analysed paired CD4 and viral
load measures from 34,384 antiretroviral-naive adult patients who received care
between 1984 and 2011.
contributed total of 158,385 paired measurements. The median age at baseline
was 34 years. Approximately three-quarters (73%) of participants were men, 34%
were white and 12% acquired HIV via injecting drug use. Median CD4
count and viral load at baseline were 477 cells/mm3 and 10,000
increased by a mean of 0.091 log10/copies/ml each year. This was
accompanied by a mean fall in CD4 count of 78 cells/mm3 per year.
Increases in viral
load were significantly greater (p < 0.001) in older patients. Each ten-year
increase in age was associated with an additional 0.022 log10/copies/ml
annual increase in viral load.
Overall, there was
no association between sex, race or injecting drug use and viral load increase.
However, there was some evidence of an age-sex interaction (p = 0.03). Viral
load increased by a mean of 0.16 log10/copies/ml each year in women
aged 55 and over, compared to a mean increase of 0.11 log10/copies/ml
among men in this older age group.
Current viral load
was the strongest predictor (p < 0.001) of CD4 decline. Each additional 1
log10/copies/ml increase in viral load was associated with a fall in
CD4 cell count of 38 cells/mm3. Strikingly, the mean annual change
in CD4 count was a fall of just 5 cells/mm3 among patients with a viral
load below 200 copies/ml, compared to a drop of 225 cells/mm3 per
year for patients with a viral load above 1 million copies/ml.
Age was a
significant factor (p < 0.05) in the rate of CD4 decline, mean count
dropping by an additional 1.7 cells/mm3 per year for each ten-year
increase in age. Sex, race and injecting drug use were not associated with CD4
decline, nor was there any evidence of an interaction between these factors.
“In our study, we
found in ART-naive individuals, faster viral load rise was associated with
older age and faster CD4 depletion was strongly associated with a higher
current viral load,” conclude the investigators. “These estimates, which
largely confirm previous observations, also provide further data on factors
associated with the natural course of HIV infection and, in particular, allow
precise characterization of the mean rate of CD4 decline to be expected
according to current viral load level.”