Individuals who start HAART when their CD4 cell count is below 200 cells/mm3 are more likely to progress to AIDS or death than patients who initiate anti-HIV therapy with a CD4 cell count between 201 – 350 cells, even if they achieve durable HIV suppression, according to US research published in the December 1st edition of the Journal of Infectious Diseases.
The study provides one of the strongest bodies of evidence to date that delaying HAART until a CD4 cell count falls below 200 cells/mm3 has a clear clinical disadvantage, and the investigators emphasise that this disadvantage should be strongly stressed in treatment guidelines.
The investigators conducted an observational study which followed 1173 patients who started HAART between July 1996 and summer 2002. Individuals were stratified according to their baseline CD4 cell counts (below 200 cells/mm3; 201 – 350 cells/mm3; and above 350 cells/mm3). Data were gathered on the number of patients achieving durable HIV suppression (a viral load below 400 copies/mL) and the development of new AIDS-defining infections and deaths.
Among all the study patients, HAART was taken for a median of 29 months, and median duration of total follow-up was 36 months.
Individuals who started HAART with a CD4 cell count below 200 cells/mm3 were significantly less likely to achieve durable HIV suppression. Even if patient with a lower CD4 cell count achieved a sustained viral load below 400 copies/mL there was a trend for them to experience more clinical events (AIDS or death) than individuals whose baseline CD4 cell count was between 201 cells/mm3 - 350 cells/mm3 (p=0.09), and were significantly more likely to progress than patients whose baseline CD4 cell count was above 350 cells/mm3 (p=0.01).
However, the investigators found no benefit was gained from starting HAART with a CD4 cell count above 350 cells/mm3 as there was no difference in disease progression between patients who stated HAART at this level and patients whose baseline CD4 cell count was between 201 cells/mm3 and 350 cells/mm3 (p=0.40).
Commenting on their findings, the investigators note that their study had a longer duration of follow-up (a quarter of individuals contributed 54 months or more of data) than the observational studies upon which current treatment guidelines are based.
They conclude that their findings “strongly support initiating therapy at CD4 lymphocyte counts >200 cells/mm3 and suggests that treatment guidelines should clearly state the importance of initiating therapy before CD4 lymphocyte counts decrease to 3.
Further information on this website
US HIV guidelines: choose either lopinavir or efavirenz in first-line treatment - news story
BHIVA treatment guidelines 2003
Further information
Early vs late initiation of antiretroviral therapy for HIV infection: a scientific roundtable meeting - a Medscape report on a US expert meeting examining recent data on this subject.
Sterling TR et al. Improved outcomes with earlier initiation of highly active antiretroviral therapy among human immunodeficiency virus-infected patients who achieve durable virologic suppression: longer follow-up of an observational cohort. Journal of Infectious Diseases 188: 1659 – 65, 2003.