Few AIDS diagnoses among people with higher CD4 cell counts, but risk remains elevated for those with a count below 750

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Incidence of AIDS-defining illnesses remains elevated even when the CD4 cell count is between 500 and 749 cells/mm3, European research published in Clinical Infectious Diseases shows.

“We found an increased rate of new ADIs [AIDS-defining illnesses] at a current CD4 count of 500-749 cells/mm3 compared to 750-999 cells/mm3 or higher but no evidence of any association between CD4 count and incidence of new ADIs within 750-999 cells/mm3, or > 1000 cells/mm3,” write the investigators.

The authors also found that “the incidence of new ADIs at higher CD4 counts was extremely low.”


AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

Kaposi's sarcoma (KS)

Lesions on the skin and/or internal organs caused by abnormal growth of blood vessels.  In people living with HIV, Kaposi’s sarcoma is an AIDS-defining cancer.


Describes tumours which grow rapidly, infiltrate surrounding tissues and spread around the body. 

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

Thanks to antiretroviral therapy, most people living with HIV in richer countries now have a normal life expectancy. The risk of most AIDS-defining illness is highest when CD4 cell count falls to below 200 cells/mm3. All HIV treatment guidelines recommend that people with this level of immune suppression should take antiretroviral therapy.

However, there are few data on the incidence in the era of modern HIV therapy of AIDS-defining illnesses at higher CD4 cell counts.

Investigators from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study therefore designed research with the aim of describing the incidence of new AIDS-defining illness among people with CD4 cell counts above 200 cells/mm3. They also wanted to establish the incidence of AIDS events at CD4 cell counts above 500 cells/mm3.

People receiving care between 1998 and 2010 with a CD4 cell count above 200 cells/mm3 were eligible for inclusion in the study. These individuals were placed into different CD4 cell categories: 200-349 cells/mm3; 350-499 cells/mm3; 500-749 cells/mm3; 750-1000 cells/mm3; and above 1000 cells/mm3.

A total of 207,539 individuals were included in the study and contributed over 1,154,800 person-years of follow-up. A total of 12,135 new AIDS-defining events were recorded.

The most common were oesophageal candidiasis (13%), Kaposi's sarcoma (11%) and pulmonary tuberculosis (10%).

Median CD4 cell count at the time of diagnosis with a new AIDS-defining illness ranged from 314 cells/mm3 among the 127 patients diagnosed with MAI to 416 cells/mm3 among the approximately 780 patients with recurrent herpes.

Overall, 5632 new AIDS-defining illnesses were diagnosed in patients with a CD4 cell count in the 200-349 cell/mm3 group and a further 3319 were among patients with a CD4 cell count between 350-499 cells/mm3. Only 1000 diagnoses involved people with a current CD4 cell count above 750 cells/mm3.

The incidence of new AIDS events was 21 per 1000 person-years of follow-up among patients with a CD4 cell count between 200-349 cells/mm3, 10.2 per 1000 person-years of follow-up for individuals with a CD4 cell count between 350-499 cells/mm3, and 6.4 per 1000 person-years for those with a CD4 cell count between 500-749 cells/mm3. This compared to a rate of just 4.7 per 1000 person-years of follow-up among those with a CD4 cell count above between 750-999 cells/mm3, with the rate falling to 4.1 per 1000 person-years for those with a CD4 cell count above 1000 cells/mm3.

Factors associated with the development of a new AIDS-defining illness when current CD4 cell count was above 500 cells/mm3 included a CD4 cell count below 750 cells/mm3 (p < 0.001), injecting drug use (male, p = 0.009; female, p < 0.001), a current viral load above 10,000 copies/ml (p < 0.001), older age (each additional ten years, p < 0.001) and a previous history of AIDS (p < 0.001).

Compared to patients with a CD4 cell count between 750-999 cells/mm3, individuals in the 500-749 cells/mm3 had a significantly higher rate of new AIDS events (aIRR = 1.20; 95% CI, 1.10-1.32; p < 0.001).

Each 50 cell/mm3 reduction in CD4 cell count for patients in the 500-749 cell/mm3 category increased the risk of a new AIDS event by a significant 6% (p < 0.001). The risk of AIDS was uniformly low for patients in the 750-999 cell/mm3 stratum and did not differ according to precise CD4 cell count.

A CD4 cell count above 1000 cells/mm3 was not associated with any further reduction in the risk of AIDS.

The investigators also found that patients with a current CD4 cell count between 500-749 cells/mm3 had a higher risk of developing a new AIDS illness even if they had an undetectable viral load.

The association between a CD4 cell count between 500-749 cells/mm3 and an increased risk of AIDS was stronger for cancer-associated diagnoses (aIRR = 1.52; 95% CI, 1.25-1.86) than non-malignant AIDS illnesses (aIRR = 1.12; 95% CI, 1.01-1.25).

“Despite the low rate of new ADIs at current CD4 counts >500 cells/mm3, the rate was increased by 20% when compared to those with a current CD4 count of 750-999 cells/mm3, whereas there was no further significant reductions in ADIs at higher CD4 counts,” conclude the authors. “These results were similar in those with viral suppression.” They believe “persons with HIV infection are not fully immune reconstituted until the CD4 count increases to >750 cells/mm3.”


Mocroft A et al. The incidence of AIDS-defining illnesses at a current CD4 count > 200 cells/mm3 in the post-combination antiretroviral therapy era. Clin Infect Dis. DOI: 10.1093/cid/cit423, 2013.