EACS: CD4 cells: the lower you start, the lower you finish

A study of UK patients presented at the eleventh European AIDS Conference (EACS) finds that patients starting antiretroviral (ARV) therapy gain roughly equal numbers of CD4 cells regardless of their initial count, except for those starting with extremely low or extremely high counts.

Patients starting treatment at low counts will probably never reach CD4 counts anywhere near normal. This adds to the weight of evidence that starting treatment earlier, before CD4 cell counts fall below 350 cells/mm³ or so, is better than waiting until counts have fallen below 200 cells/mm³ .

The UK CHIC cohort is a cohort of over 17,000 UK HIV patients. For the purposes of this study, patients were selected from the cohort who had started ARV therapy between the beginning of 1998 and the end of 2005 and who had maintained undetectable viral loads from six months after the start of treatment to the end of the study. They had to have had at least one pre-treatment CD4 count and another one at least six months after the start of therapy (in practice, the average number of CD4 counts done per patient was 13). They also needed annual viral load measuremenst to be included.

Over 4,100 patients met the testing criteria of which 2,780 (67.6%) maintained undetectable viral loads through to the end of 2005.

The study found that the pre-treatment (baseline) CD4 count varied according to the type of patient. For instance, gay men comprised only 38% of those starting with the lowest CD4 counts (below 25 cells/mm³), but 75% of the 91 patients starting treatment with CD4 counts over 500 cells/mm³. Conversely, heterosexuals formed 56% of those starting treatment with counts under 25 cells/mm³ but only 18% of those starting treatment with more than 500 cells/mm³. In general, a higher proportion of those starting treatment with CD4 counts below 200 cells/mm³ were female, African and heterosexual.

The cumulative CD4 increases for each stratum of baseline CD4 count are best summarised in a table:

It can be seen that those with the very lowest baseline CD4 counts had the highest increases on ARVs, while those with the very highest had the lowest increases.

However there was relatively little variation in CD4 increase in those in the middle strata, with patients with 25-50 CD4 cells only gaining 40 more CD4 cells than those starting with 350-500 CD4 cells. The eventual CD4 cell count is therefore much more dependent on the baseline count than on variations in the rate of increase while on treatment, and only those starting treatment with counts above 350 cells/mm³ achieved CD4 counts nearing normality for people without HIV.

The median CD4 count at year five was 169 cells lower in those starting with 25-50 CD4 cells than in those starting with 200-350, and it was 121 higher in those starting treatment with 350-500 cells.

The rate of CD4 increase declined every year, and again there was remarkable consistency for all but those starting at the highest or lowest CD4 counts. The average CD4 count gain in the first year, in all baseline groups except those starting with more than 500 cells, was between 172 and 181 cells (those starting with over 500 gained only 98 cells).

In the second year the vast majority of patients, namely those starting at counts anywhere between 25 and 350, gained between 52 and 69 cells; in year three between 30 and 43 cells; in year four 19 to 29 cells; in year five 13 to 21 cells. CD4 cell gains in patients starting at counts below 25 were consistently higher (in the region of 12 more cells a year than any other group, apart from in the first year), and patients starting over 500 consistently lower.

There is of course huge individual variation concealed within these average figures. However the fact that the rate of CD4 increase, in all patients in this large cohort, consistently slowed down from year to year brings with it the sobering conclusion that patients who start therapy with low CD4 counts will never, at least on standard antiretroviral therapy, regain all the immune function that HIV took away.