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Most patients on potent combination antiretroviral therapy achieve undetectable viral loads, but CD4 responses to therapy are more heterogeneous. In this study (previously reported at the 13th Retrovirus Conference), investigators analyzed CD4-cell counts in a large group of patients with sustained virologic suppression.
Eligible patients were identified from the Johns Hopkins HIV Clinical Cohort based on the following criteria: (1) receipt of potent PI- or NNRTI-based combination therapy; (2) sustained virologic suppression to <400 copies/mL for at least 6 months; and (3) no history of treatment interruption. If viral rebound occurred after suppression, data were censored to record the CD4-cell count at the last visit before rebound.
A total of 655 patients met the inclusion criteria; their median treatment duration was 46 months (range, 13–72 months). When stratified by baseline CD4 count (<200 cells/mm3, 200–350 cells/mm3, >350 cells/mm3), patients with >350 cells/mm3 had lower viral loads, were less likely to be black or to use injection drugs, and were more likely to have acquired HIV through male-to-male sexual contact. They were also more likely to be treated with an NNRTI-based regimen than with a PI-based one.
After 6 years of treatment-induced virologic suppression, patients in the three strata achieved the following median CD4-cell counts:
493 cells/mm3 among those who started treatment with <200 cells/mm3,
508 cells/mm3 among those who started treatment with 201–350 cells/mm3, and
829 cells/mm3 among those who started treatment with >350 cells/mm3.
“Normal” CD4-cell counts (≥750 cells/mm3) were achieved by 12%, 21%, and 46% of the three groups, respectively. All three groups experienced a plateau in CD4-cell increase after 4 years of therapy, with no significant increase after this point. Multivariate analysis revealed that a higher baseline CD4-cell count predicted a better CD4 response, whereas injection drug use and older age predicted a lower one. No differences were seen based on type of therapy (NNRTI- vs. PI-based) or coinfection with hepatitis C virus.
Moore RD and Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 2007 Feb 1; 44:441-6.
Comment
The strengths of this analysis are the relatively large sample size and the long-term follow-up, with the latter allowing for a clear description of a CD4 plateau effect. Although one could argue that the difference between a “final” achieved CD4 count of approximately 500 cells/mm3 versus 800 cells/mm3 is not clinically meaningful, such a difference could have important implications for the development of neoplastic and chronic inflammatory complications. In addition, we should remember that each of the median values in this study describes a range of CD4 responses, with the lowest strata including individuals with persistently low CD4-cell counts despite virologic suppression. These findings — and those from a similar study in Europe [Abstract 530, 13th Retrovirus Conference, Denver, 2006] — are already widely cited as evidence supporting a higher CD4 threshold for initiating antiretroviral therapy in asymptomatic patients.