Long term antiretroviral therapy may restore CD4 cell counts in HIV positive patients

HIV positive patients who take combination antiretroviral therapy (cART) to combat HIV infection could see the numbers of CD4 cells in their immune system rise to concentrations found in HIV negative individuals, if they remain on the therapy for long enough and their HIV viral load load is suppressed to below 50 copies per ml.

The findings are reported in an Article published early Online and in an upcoming edition of the Lancet.

However an accompanying Comment cautions the findings are only applicable to patients having periods of maximum virological suppression, and thus have limited application in low income countries.

Dr Amanda Mocroft, Royal Free Centre for HIV Medicine, Royal Free and University College London Medical Schools, and colleagues did a study of 1835 antiretroviral-naive patients from EuroSIDA, a pan-European observational cohort study. These patients, with a mean CD4 cell count of 204 cells per microlitre of blood, then started cART. They were selected because they all responded well to cART and their HIV viral loads were suppressed to below 50 copies per ml for extended periods of time.

The researchers found that the greatest average yearly increase in CD4 count of 100 cells per microlitre was seen in the year immediately following the start of cART. Significant, but lower, yearly increases of around 50 cells per microlitre were seen even five years after beginning cART in some cases, in which patients whose current CD4 count was below 500 cells per microlitre. Patients starting cART with low CD4 cell counts (of less than 200 cells per microlitre) had substantial rises in CD4 counts even after five years. The only groups without substantial increases in CD4 count were those where cART had been taken for more than five years with a current CD4 count of more than 500 cells per microlitre.

The authors conclude: “Normalisation 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.

“We have shown that most patients with HIV who can maintain viral load at less than 50 copies per ml continue to have significant rises in CD4 counts, even after protracted exposure to combination therapy.

“Patients who started cART with a CD4 cell count of more than 350 cells per microlitre 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.”

In the accompanying Comment, Dr Gary Maartens and Dr Andrew Boulle, University of Cape Town, South Africa, point out that CD4 cell count when patients start cART is the most important factor is predicting survival – not count increases after cART has begun.

They say: “Mocroft and colleagues’ findings that CD4 counts continue to increase on cART until normal values are reached, even with low CD4 counts at baseline, is only generalisable to patients on cART during periods of maximum virological suppression.”

They conclude: “Nevertheless, the researchers have shown that at least for patients with ideal responses to cART, normalisation of CD4 counts is likely to be achievable across a range of baseline counts.”