Long-Term HIV Suppression Leads to Sustained Increases in CD4 Count

LONDON, July 19 -- Most HIV-infected patients can achieve normal CD4 counts if maximal virologic suppression can be maintained long enough, investigators in a European observational study have concluded.
Patients whose viral load decreased to less than 50 copies/mL and was maintained at that level had sustained annual increases in their CD4 count, even after five years of combination antiretroviral therapy (cART), according to an article in the July 19 issue of The Lancet. Combination therapy was defined as two nucleosides or nucleotides plus a single protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or abacavir.
The only patients who did not have sustained increases in CD4 count were those who had received combined therapy for more than five years and had a current CD4 count of more than 500 cells/µL, reported Amanda Mocroft, M.D., of the Royal Free and University College Medical School here, and colleagues
"Patients who started cART with a CD4 cell count of more than 350 cells per microliter had CD4 cells counts approaching the level seen in HIV-negative individuals after more than three years of cART and had no further significant rises in CD4 counts," they wrote.
"Normalization of CD4 counts in HIV-infected patients for all infected individuals . . . might be achievable if viral suppression with cART can be maintained for a sufficiently long period of time," the investigators concluded.
According to current treatment guidelines for HIV infection, the goal of combination antiretroviral therapy is to reduce viral replication below the level of detection, the authors noted. As viral replication falls, the CD4 count increases.
However, little research has focused on CD4 count increases in analyses restricted to patients with maximum virologic suppression (less than 50 copies/mL), they said.
So Dr. Mocroft and colleagues reviewed data on a subset of 1,835 patients enrolled in the EuroSIDA observational cohort study. Patients included in the analysis were antiretroviral naïve and started combination antiretroviral therapy in the EuroSIDA study. Each patient had CD4 count measured before starting combination therapy and two consecutive viral load measurements of less than 50 copies/mL after starting therapy.
After stratification of data by current CD4 count, the investigators calculated the annual unadjusted rate of increase. The rate of increase ranged from a low of 37 cells/µL per year in patients with a current CD4 count of 501 to 600 cells/µL to a high of 74 cells/µL in patients with a current CD4 count of 200 cells/µL or less. The only patients who did not have significant increases were those whose current CD4 counts exceeded 700 cells/µL (18 cells/µL/year).
In an adjusted analysis, patients with a current CD4 count of less than 700 cells/µL had an annual increase in CD4 count that averaged 40 to 60 cells/µL with continued suppression of viral load to less than 50 copies/mL. Even patients with higher CD4 counts had significant, though smaller, annual increases (24 cells/µL, P=0.047).
Stratification of the adjusted data by current CD4 count and years since starting combination antiretroviral therapy showed that only patients who did not have significant annual increases in CD4 count were those who had a current count greater than 500 cells/µL and who had been treated for more than 5 years.
In a commentary that accompanied the article, Gary Maartens, M.D., and Andrew Boule, M.D., of the University of Cape Town, South Africa, pointed out that of the known factors when combination antiretroviral therapy is initiated, the CD4 count at the start of treatment remains the most important predictor of survival in HIV patients.
The finding that "CD4 counts continue to increase on cART until normal values are reached . . . is only generalizable to patients on cART during periods of maximum virologic suppression," the editorialists noted.
Nonetheless, they said, the study showed that "at least for patients with ideal responses to cART, normalization of CD4 counts is likely to be achievable across a range of baseline counts."
Primary support for EuroSIDA is provided by the European Commission. Multiple commercial interests also have contributed. The Swiss Federal Office for Education and Science funded participation by Swiss centers. The authors disclosed multiple commercial relationships. Drs. Maartens and Boulle declared no conflicts of interest. Primary source: The LancetSource reference: Mocroft A et al. "Normalization of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study." The Lancet 2007;epub. Additional source: The LancetSource reference: Maartens G and Boulle A. "CD4 T-cell responses to combinatioin antiretroviral therapy." The Lancet 2007;epub.