The average CD4
cell count of people newly entering HIV care in resource-rich countries did
not increase meaningfully between 1992 and 2011, results of a systematic review
published in Clinical Infectious Diseases
“Many people with HIV
infection in high income-countries present late for care and may start
treatment even later,” said Professor Joep Lange of the Netherlands in an
accompanying editorial. “The finding that so little has changed with regard to
time of presentation to HIV care in a period that saw dramatic improvements in
HIV treatment and monitoring is astonishing.”
CD4 cell count is
used to monitor the immune status of people with HIV. Late diagnosis is
defined as presentation with a CD4 cell count below 350 cells/mm3, the
minimum threshold for starting antiretroviral therapy. Diagnosis is very late
if CD4 cell count is below 200 cells/mm3, therefore showing a high
risk of AIDS-related illnesses.
It is well known
that the timing of HIV diagnosis can have profound individual and public health
consequences. Late diagnosis is a factor underlying much of the HIV-related
illness and death that continues to be seen in resource-rich countries.
In addition, there's evidence that undiagnosed individuals are responsible for a disproportionately large number
of new HIV transmissions. Late diagnosis is also expensive to healthcare
A team of
investigators from the United States and United Kingdom wanted to see if the
immune status of adults newly entering HIV care in richer countries changed between
1992 and 2011. They therefore
conducted a systematic review of studies reporting on CD4 cell count at the
time of entry to care.
knowledge,” comment the authors, “no systematic review has assessed temporal
trends in the clinical status of persons presenting to HIV care across cohorts
in developed countries.”
During the twenty-year
period of the study, there were major advances in HIV diagnostics, monitoring,
care and treatment, especially the introduction of effective, tolerable and
easy-to-take antiretroviral combinations.
conducted a database search in late 2011, identifying peer-reviewed studies
published between 2000 and 2011 that reported on the CD4 cell count of people
newly entering HIV care.
A total of 44
studies with 169,000 patients met their inclusion criteria. Most of these
involved patient cohorts in the United States (18) or the United Kingdom (11).
The mean CD4 cell
count of people entering care in 1992 was 307 cells/mm3. There was
an estimated increase of 1.5 cells/mm3 each year, and in 2011 the
mean CD4 cell count of people newly entering care was 336 cells/mm3. These findings
remained essentially unchanged in a series of sensitivity analyses.
also showed there were only minimal changes in the proportion of people presenting late or very late. In each case there was a reduction of only 0.1%
believe their findings have significance for debates about the use of
antiretroviral treatment as prevention: “The promise of such approaches is
unlikely to be realized unless improvements in timeliness of HIV diagnosis and
presentation for care are achieved, dramatically altering the trajectory of the
temporal trends observed over the past 2 decades.”
There is also
controversy about whether HIV therapy should be started at a CD4 cell count of
350 cells/mm3 or the higher level of 500 cells/mm3. “Our
study findings indicate that the considerations of when to start may be
immaterial for the majority of patients who continue to enter care below any of
the recommended treatment thresholds,” comment the authors.
They conclude: “New
and innovative strategies to identify persons earlier in the course of their
HIV infection and link them promptly with medical care are clearly necessary
and desperately needed to fully realize the individual and public health
benefits afforded by contemporary HIV treatment.”
echoes this conclusion in his editorial. “We need to increase HIV testing…we
need to direct our efforts primarily at those populations most at risk of HIV
infection, and repeatedly test those found to be HIV negative,” writes Lange.
“In those found to be infected, we need to spell out clearly, and again and
again, the importance of early treatment for their own health, beside that of
minimizing the risk of onward HIV transmission.”