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Increased Risk of AIDS-defining Illnesses Seen Even at CD4 Counts of 500-750

HIV positive people with CD4 T-cell counts in the 500-749 cells/mm³ range still have a higher risk of AIDS-defining illnesses -- especially cancers -- compared to those with more than 1000 cells/mm³, although the risk is quite low, according to a study published in the August 6, 2013, advance edition of Clinical Infectious Diseases. These findings offer further evidence of the benefits of prompt antiretroviral treatment.

It is well known that the incidence of opportunistic infections and cancers rises steeply once a person's CD4 count falls below 200 cells/mm³. The risk of HIV disease progression and death increases below 350 cells/mm³ as well, with smaller disadvantages apparent below 500 cells/mm³ -- the lower end of the normal range for healthy HIV negative people. Outcomes among HIV positive people with higher CD4 levels, however, have not been extensively studied. Current U.S. antiretroviral therapy (ART) guidelines recommend that anyone diagnosed with HIV should be offered treatment, regardless of CD4 count.

Amanda Mocroft andfellow investigators with the EuroCOORD Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study team looked at occurrence of AIDS-defining conditions among cohort participants at different CD4 cell strata: 200-349, 350-499, 500-749, 750-1000, and >1000 cells/mm³.

The analysis included 207,539 cohort participants age 14 or older with at least 1 CD4 cell measurement of >200 cells/mm³ between 1998 and 2010. Collectively they contributed more than 1 million person-years (PY) of follow-up data.

Results

• A total of 12,135 new AIDS-defining illnesses occurred among people with >200 cells/mm³ during 1,154,803 PY of follow-up.
• Nearly half of these occurred among people with 200-349 cells/mm³ and another quarter among those with 350-499 cells/mm³.
• The most common AIDS-defining illnesses were esophageal candidiasis (13%), Kaposi sarcoma (11%), and pulmonary tuberculosis (10%).
• As expected, incidence rates of AIDS-defining illnesses fell as current CD4 count rose:

o   20.5 per 1000 PY for people with 200-349 cells/mm³;

o   10.2 per 1000 PY for those with 350-499 cells/mm³;

o   6.4 per 1000 PY for those with 500-749 cells/mm³;

o   4.7 per 1000 PY for those with 750-999 cells/mm³;

o   4.1 per 1000 PY for those with >1000 cells/mm³.

• People with a current CD4 count in the 500-749 cells/mm³ range had a significantly higher rate of AIDS-defining illnesses than those with 750-999 cells/mm³ (adjusted incidence rate ratio [IRR] 1.20).
• The difference was more apparent for AIDS-defining cancers (adjusted IRR 1.52) than for non-malignant illnesses (adjusted IRR 1.12)
• Within the 500-749 cells/mm³ range, each further 50 cell reduction was associated with a 6% increase in the risk of AIDS-defining illnesses.
• People with current CD4 levels >1000 cells/mm³, however, had an AIDS-defining illness rate similar to that of people with 750-999 cells/mm³ (adjusted IRR 0.92), indicating no further improvement above this level.
• These findings were consistent when considering people with either high or low HIV viral load levels.
• Other factors significantly associated with developing AIDS-defining illness at CD4 counts >500 cells/mm³ included older age, history of injection drug use, and prior AIDS diagnosis.

"The incidence of AIDS-defining illnesses was higher in individuals with a current CD4 count of 500-749 cells/[mm³] compared to those with a CD4 count of 750-999 cells/[mm³], but did not decrease further at higher CD4 counts," the study authors concluded.

"Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/[mm³]," they added.

8/28/13

Reference

A Mocroft, HJ Furrer, JM Miro, et al (COHERE study in EuroCOORD). The Incidence of AIDS-Defining Illnesses at a Current CD4 Count >200 Cells/µL in the Post–Combination Antiretroviral Therapy Era. Clinical Infectious Diseases. August 6, 2013 (Epub ahead of print).