Starting antiretroviral (ARV) treatment before CD4 counts drop to 350 or below results in the restoration of immune cell numbers to near normal levels in people with HIV, according to a study published online January 5 in Clinical Infectious Diseases.

During the early years of combination ARV treatment, complex dosing and side effects prompted treatment guidelines experts to hold off on recommending HIV treatment until CD4 counts fell below 200 to 350. With the availability of easier and safer medications, along with research showing that earlier treatment may reduce the risk of non-AIDS related illnesses such as cardiovascular disease, experts are now eyeing the possibility of recommending therapy while the CD4 count is above 350. However, no studies have determined whether starting therapy earlier will help patients keep their CD4s well within the normal range, thus further reducing the risk of typical HIV-related problems.

To explore this, Gregory Robbins, MD, MPH, from Harvard Medical School in Boston, and his colleagues examined data from an AIDS Clinical Trials Group (ACTG) study. The study, called ACTG 384, enrolled 978 people with HIV who were about to start ARV treatment for the first time. Researchers were able to examine comprehensive information on a number of different immune cells for 621 of the study volunteers. Details included not only absolute CD4 numbers, but also the number and ratio of CD4 naïve and memory cells, CD8 cells and B cells.

Robbins’s team found that the CD4 count at which people initiated treatment mattered a great deal. On average, most people saw substantial increases in their CD4 counts after three years of treatment. However, among those starting treatment with 350 or fewer CD4s, few saw their CD4s, CD8s and ratios achieve levels typically seen in people not infected with HIV. But among those who started treatment before their CD4s dropped to 350, most achieved and maintained normal or near normal levels.

Although the study was not designed to determine whether restoring immune cells to normal levels actually translates into health and survival benefits, the authors state that the results lend weight to arguments in favor of starting ARV therapy earlier. They also argue that looking at detailed analysis of various immune cell counts and ratios, and not just overall CD4 cell count increases, should become a standard part of judging ARV therapy success.

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