HIV-positive patients beginning antiretroviral therapy after their CD4 counts have fallen to below 200 cells/mm3 are less likely to exhibit full immune reconstitution than those who start with more CD4 T-cells, according to findings presented in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes. However, the study confirms that suppression of viral load is the best indicator of successful therapy.
Current HIV treatment guidelines recommend delaying HAART until CD4 T-cell counts have fallen to around 200 cells/mm3 in patients without symptoms, in order to avoid the side-effects associated with therapy and the development of drug resistance. However, there is some concern that delaying therapy may result in reduced chances of complete immune recovery and that there may be a ‘threshold’ below which HAART becomes less effective.
The study’s authors wished to assess how baseline CD4 counts, viral load and age affected long-term CD4 cell recovery in patients starting antiretroviral therapy. They followed the 861 HIV-positive patients from Hospital Clínic in Barcelona, Spain, who started HAART with three drugs (two NRTIs and one protease inhibitor; three NRTIs or 2 NRTIs and one NNRTI) in or after 1996.
The investigators monitored the patients’ viral loads and CD4 counts for six months prior to HAART, and every three months after initiation of therapy, for a median of 173 weeks. The patients were divided into four groups according to their baseline CD4 count: fewer than 200 cells/mm3; 200 - 349 cells/mm3; 350 - 499 cells/mm3; and more than 500 cells/mm3.
Overall, CD4 T-cell counts increased from a median of 214 to 499 cells/mm3 (p 3 in 85 (21%) of the patients with fewer than 200 cells/mm3 at baseline. This compares with 16 (7%) of the patients starting with 200 - 349 cells/mm3, and none of those starting with over 350 cells/mm3 (p
Conversely, 113 (28%) of the patients with baseline CD4 counts below 200 cells/mm3 achieved final CD4 counts of over 500 cells/mm3. This is in contrast to 132 (58%) of the patients starting with 200 - 349 cells/mm3, 109 (80%) starting with 350 - 499 cells/mm3 and 76 (84%) of those with over 500 cells/mm3 at baseline (p
All four groups of patients exhibited similar increases in CD4 T-cell counts over the course of the study, leading the authors to suggest that the number of CD4 T-cells before starting therapy does not have a strong influence on the possible CD4 count rise. However, starting from a lower baseline seems to reduce the highest CD4 count patients can reach.
“Our study suggests that there is not a ‘point of no return’ when HAART is used in naïve patients regardless of baseline CD4+ T-cell counts when the therapy was started.” However, “patients who started therapy with a CD4+ T-cell count 3 had a higher risk of having a last determination of CD4+ T-cell count low enough to allow the development of some opportunistic infections than patients with a higher baseline CD4+ T-cell count.”
The increase in CD4 cell counts was maintained for up to four years of follow-up. The rise was quickest in the first year of HAART, slowing down after three years and reaching a plateau after four to five years of therapy. This trend was observed across all baseline CD4 counts, even in the patients who achieved and maintained undetectable viral loads.
When they compared patients according to final viral load measurements, the authors observed a higher increase in CD4 counts in patients with an undetectable viral load (
The authors also examined the effect of age on final CD4 cell counts, finding that 55% of the patients under the age of 40 when starting HAART achieved CD4 counts greater than 500 cells/mm3, compared with 40% of those over 40 (p 3 narrowly missed statistical significance (90% vs. 85%; p = 0.06).
As expected from the patients’ final CD4 counts, a higher proportion of the patients starting therapy with fewer than 200 cells/mm3 developed AIDS or died during the study than those in the remaining three groups (p
These findings generally support those of previous similar studies, which have used smaller cohorts of patients, shorter periods of follow-up or antiretroviral-experienced patients, or which have selected patients having a good response to treatment.
Further information on this website
Summary: when to start treatment - overview of key issues
HIV therapy - patient information booklet
Adherence, not baseline CD4 cell count, linked to CD4 cell gain on HAART - news article
Better clinical outcomes if HAART started before CD4 cell count falls below 200 - news article
Reference
García F et al. Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count. J Acquir Immune Defic Syndr 36: 702-713, 2004.