Annual CD4 count monitoring may be sufficient for people taking antiretroviral treatment who have a suppressed viral load and a CD4 count above 250 cells/mm3, investigators report. Their study showed that people in this situation had a very low risk of experiencing a drop in their CD4 count below 200 cells/mm3 or of developing a serious HIV-related illness.
The probability of a decline in CD4 cell count to below 200 cells/mm3 did not differ according to whether people were monitored annually or every six months. “This suggests,” write the authors, “that less frequent CD4 measurement does not miss important immunological events in patients with viral suppression.”
The CD4 count is one of the key tests used to monitor health for people living with HIV. A consideration of CD4 count is often crucial in reaching a decision about when to start HIV treatment. But how often should people taking treatment have their CD4 count monitored?
Some guidelines recommend that people on stable, virologically suppressive therapy should have their CD4 count monitored every six to twelve months. But recent research has shown that people doing well on antiretroviral treatment are highly unlikely to experience a drop in their CD4 count to dangerous levels (below 200 cells/mm3, indicating a high risk of potentially life-threatening opportunistic infections). It may well be the case, therefore, that less frequent CD4 testing, or monitoring driven by clinical symptoms, may be appropriate for people with viral suppression.
To further address this question, an international team of investigators looked at rates and predictors of CD4 decline to below 200 cells/mm3 and examined the effect of the frequency of CD4 monitoring in approximately 1500 people with suppressed viral load in the Asia-Pacific region.
All the study participants were enrolled in the TREAT Asia HIV Observational Cohort. To be eligible for inclusion, they were required to have been on triple-drug HIV treatment for at least six months; have sustained viral suppression (two consecutive viral load measurements below 400 copies/ml); a CD4 count of 200 cells/mm3 or above; and a minimum of one subsequent viral load below 400 copies/ml at least twelve months after viral suppression was first confirmed. Study endpoints were a single CD4 count below 200 cells/mm3; a confirmed CD4 count below 200 cells/mm3 (two confirmed counts below this level); or the development of a serious HIV-related illness.
Study participants were enrolled between 2003 and 2013. Median age at viral suppression was approximately 40 years. Most of the participants (73%) were male and 43% had a previous Aids-defining illness. Median baseline CD4 count was 393 cells/mm3. Participants were stratified according to their CD4 count: 200-249; 250-299; 300-349; 350-499; above 500.
As expected, CD4 count gradually increased during viral suppression and reached a plateau after 48 months. People with a mean baseline CD4 count of 250 cells/mm3 had a mean count of 400 cells/mm3 at the 48-month follow-up interval. The overall rate of a single fall in CD4 count to below 200 cells/mm3 was 3.45 per 100 person-years; the rate of confirmed CD4 decline to below this level was 0.77 per 100 person-years. Lower still was the rate of clinical failure – development of a serious HIV-related illness – at just 0.54 per 100 person-years.
“There were only 23 events during total 4,057 patient years without any case of death,” note the authors. People with a baseline CD4 count between 200 and 250 cells/mm3 were significantly more likely to experience a confirmed drop in CD4 count below 200 cells/mm3 compared to people with baseline CD4 counts above 500 cells/mm3 (HR = 55.47; 95% CI, 7.36-418.20, p < 0.001). There was no significant difference in risk when comparing people with CD4 counts of at least 250 cells/mm3 with people who had counts above 500 cells/mm3.
The investigators constructed a model that allowed them to compared the risk of confirmed CD4 decline to below 200 cells/mm3 according to whether monitoring was annual or biannual. The frequency of testing did not affect the risk of a serious immune decline.
Significant cost savings might be achieved by reducing the frequency of CD4 cell monitoring for people who are stable on treatment. One US study showed that annual rather than biannual testing for people with an undetectable viral load could save in excess of $10m annually. “Another benefit is to reduce patient anxiety regarding transient decline in CD4,” suggest the authors.
“CD4 testing at 6-month intervals offered no benefit over annual testing in detecting confirmed CD4 250 cells/mm3 may be sufficient for clinical management.2