Considering both CD4 cell count and CD4 cell percentage may help physicians and patients decide when is the best time to initiate HIV therapy, a study published in the February 1st edition of the Journal of Infectious Diseases has found. Investigators found that both CD4 cell count and CD4 cell percentage at the time antiretroviral therapy was started were significantly associated with the risk of HIV disease progression, and that some patients with relatively high HIV CD4 cell counts, but lower CD4 cell percentages had a higher risk of disease progression than patients with low CD4 cell counts, but higher CD4 cell percentages.
Another recently published study has also indicated the prognostic value of CD4 cell percentages. It found that CD4 cell percentages were a more reliable indicator of immunological status in individuals coinfected with HIV and hepatitis C virus.
The best time to start anti-HIV therapy is still not known. Most treatment guidelines, including those of the British HIV Association (BHIVA), make recommendation based upon patients’ CD4 cell counts - current British guidelines state that individuals whose CD4 cell count has fallen to 250 – 200 cells/mm3 should initiate HIV therapy.
It is uncertain if considering CD4 cell percentages in addition to CD4 cell count would enhance understanding of prognosis and assist physicians and patients making decisions about the initiation of HIV treatment. Studies exploring the prognostic value of using both CD4 cell counts and CD4 cell percentages have yielded inconsistent results, or have been hampered by small patient samples.
To try and clarify this issue, investigators from the ongoing CHORUS study in the United States therefore designed an observational study involving just under 1,900 individuals who started potent antiretroviral therapy between 1997 and 2005. Demographic data were obtained, CD4 cell count and CD4 cell percentage before the initiation of HIV therapy were measured, and new AIDS-defining events or death were measured.
Most of the patients (89%) were male, white (72%) and gay (72%). Mean baseline CD4 cell count was 240 cells/mm3, and mean CD4 cell percentage before the initiation of potent HIV therapy was 16%. A significant proportion of patients (29%) had progressed to AIDS and 53% had taken some form of suboptimal HIV therapy before commencing potent antiretroviral therapy. Median baseline viral load was 50,000 copies/ml.
A total of 468 AIDS-defining events or deaths were recorded during the study. They established that CD4 cell percentage at baseline was a significant, independent predictor or HIV disease progression (p = 0.02).
For example, their model predicted that a patient with a baseline CD4 cell count of 240 cells/mm3 and a CD4 cell percentage of 9% had a 65% greater risk of death during follow-up than an individual with the same CD4 cell count and baseline characteristics, but a CD4 cell percentage of 24%.
Furthermore, their model also predicted that a patient with a CD4 cell count of 350 cells/mm3, but a CD4 cell percentage of 14% had a slightly higher risk of HIV disease progression than an individual with similar demographic but a baseline CD4 cell count of 200 cells/mm3 and a CD4 cell percentage of 28%.
“Thus, there may be persons with an absolute CD4 levels above 200 cells/mm3 who could derive greater benefit from earlier initiation of [HIV therapy] than do others”, comment the investigators, adding, “CD4 percentage may identify such persons and clarify the optimal timing for the initiation of [HIV therapy].”
It should be stressed, however, that the investigators also found that individuals with a CD4 cell count of 200 cells/mm3 had a significantly greater risk of HIV disease progression than patients who started HIV therapy with a CD4 cell count above 350 cells/mm3 (p = 0.002). They also established that injecting drug users had a higher risk of disease progression than other HIV transmission groups (p
“Absolute CD4 cell count and CD4 percentage should be considered when decisions are made regarding which patients may benefit most from earlier initiation of therapy”, conclude the investigators.
Hulgan T et al. Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy. J Infect Dis 195: 425 – 431, 2007.