CD4 cell count at time of entry to HIV care did not increase significantly between 1992 and 2011

Major implications for debates about treatment as prevention and when to start therapy
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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 show.

“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.


systematic review

A review of the findings of all studies which relate to a particular research question and which conform to pre-determined selection criteria. 


When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 


Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

inclusion criteria

The conditions which a person must meet to join a research study.


peer review

The process of subjecting a scientist’s research to the scrutiny of other scientists working in the same field. Studies published in medical journals are usually peer reviewed, whereas conference presentations are not.

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 systems.

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.

“To our 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. 

The investigators 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.

The investigators 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% each year.

The authors 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.”

Professor Lange 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.”

Lesko CR et al. A systematic review and meta-regression of temporal trends in adult CD4+ cell count at presentation to HIV care, 1992-2011. Clin Infect Dis, doi: 10.1093/cid/cit421, 2013.

Lange JMA Under the spell of the Red Queen. Clin Infect Dis, doi: 10.1093/cid/cit425, 2013.