Restoring the immune system
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With effective antiretroviral therapy, many patients can achieve overall CD4 cell counts approaching those of healthy HIV-negative individuals. These vary from person to person, but are usually between 500 and 1500 cells/mm3.

A recent analysis of nearly 2000 participants in the EuroSIDA cohort, for example, found that CD4 cell counts increased by an average of 100 cells/mm3 during the first year of therapy in patients whose viral load was suppressed below 50 copies/ml. Smaller increases of about 50 cells/mm3 continued for five or more years, until patients attained levels above 500 cells/mm3 The researchers suggested that normalisation of CD4 counts might be possible for most or all HIV-positive individuals if viral suppression with HAART can be maintained for a sufficiently long period [1].

But other studies have found that people with low pre-treatment CD4 cell counts may not be able to reach normal levels, even with continued therapy. Looking at more than 5000 treatment-naive participants in the Netherlands ATHENA Cohort, researchers found that about 75% of those who started HAART with baseline CD4 cell counts above 350 cells/mm3 eventually attained 800 cells/mm3 or more, but the rate was about 50% for those who started treatment with 200 to 350 cells/mm3, and only about 25% for those who started with fewer than 200 cells/mm3[2].

In an analysis of French patients who maintained a viral load below 500 copies/ml on HAART for five years, 83% of those who started treatment with CD4 cell counts of 200 cells/mm3 or higher - but only 45% of those with lower baseline levels - went on to achieve CD4 counts above 500 cells/mm3[3]. Similarly, in the ACTG 384 trial, patients who began treatment with more than 350 CD4 cells/mm3 usually attained normal levels, but those who started with lower counts did not catch up during the 144-week follow-up period[4].

Another research team found that while treatment-naive individuals who started HAART with CD4 cell counts below 50 cells/mm3 continued to experience immune recovery for up to seven years, their CD4 cell counts did not reach those of patients who started therapy with higher pre-treatment levels[5].

Studies also show that treated patients can recover both naive CD4 T-cells and a diverse set of memory CD4 T-cells that respond to a wide variety of antigens. But patients who start treatment with very low ‘nadir’ (lowest-ever) CD4 cell levels may not experience complete restoration of a full range of memory responses to previously encountered pathogens [6][7].

Taken together, these studies suggest that starting treatment early - before advanced immune suppression occurs - can improve long-term outcomes. This issue is discussed in Starting HIV treatment.