Taking HAART for over three years doesn’t lead to any additional suppression of HIV or significant gain in CD4 cells according to French research published in the January 2nd edition of the journal AIDS. One the basis of these findings the investigators question the benefits of very long-term use of HAART.
Investigators at the Necker Hospital in Paris conducted a retrospective analysis of the records of 41 patients who, after starting HAART, had maintained an undetectable viral load below the limit of detection (50 copies/mL) with a minimum follow-up of at least 48 months after the initiation of HAART. Individuals were followed up for a median of 60 months.
To determine the level of ongoing HIV replication, the investigators measured HIV DNA in peripheral blood mononuclear cells (PBMC) in 25 individuals. Levels of HIV DNA in PBMC allowed researchers to estimate the size of the HIV viral reservoirs.
All the patients started HAART between May 1996 and April 1997, and all achieved an undetectable viral load within six months of starting therapy. All the patients initially took a regimen including two nucleoside analogues and a protease inhibitor, and after a median of 60 months of follow-up, 48% of patients were still taking their initial regimen and 87% were taking a protease inhibitor.
The average age of the study participants at baseline was 36 years, the median duration of diagnosed HIV infection prior to the initiation of HAART was five years, 11% had progressed to AIDS, and 61% had taken antiretroviral therapy prior to the use of HAART.
At baseline, median CD4 cell count was 135 cells/mm3, at which time median viral load was 4.58 log10 copies/ml.
After five years of follow-up, median CD4 cell count had increased to 604 cells/mm3. However, CD4 cell gains were greatest during the first 18 months of HAART (mean 168 cells/mm3), with less pronounced gains thereafter (mean 38 cells/mm3).
A total of 30 individuals achieved a constant CD4 cell count above 400 cells/mm3, a point which the investigators selected as indicative of sufficient immune function to provide protection against symptomatic HIV disease. A quarter of individuals achieved this endpoint within 18 months of stating HAART, and 56% (23 individuals) had a constant CD4 cell count above this level by month 42, increasing to 69% (33 patients), by month 66.
The overwhelming majority of individuals (87%) who achieved a CD4 cell count above 400 cells/mm3 by month 18 kept a CD4 cell count above this level for three years, and over 93% of individuals with a CD4 cell count above 400 cells/mm3 after three years of HAART still had a CD4 cell count of this level at year five.
HIV viral load fell by a median of 0.48 log10 copies/ml in the first year of HAART, and by an additional 0.18 log10 copies/ml in both years two and three, with no further significant falls thereafter.
Although no patients died during the median five years of follow-up, two individuals did die at month 61, one of liver-related causes and one of lymphoma. Both individuals had an undetectable viral load at death.
"The present study…stresses the levelling off, with time, of the effects of HAART", comment the investigators. For patients with a sustained CD4 cell count above 400 cells/mm3 after three years of HAART, the investigators ask, "would it be reasonable to consider stopping therapy when the level of HIV DNA reaches its lowest plateau and then wait for the patients to meet again the criteria for treatment initiation? Trials should be designed to compare this long-term strategy for prolonged periods on and off therapy with the standard attitude to maintaining HAART and with structured treatment interruptions with a shorter time scale."
Further information on this website
Restoring the immune system - overview of research
CD4-guided treatment interruption - overview of studies looking at the effects of stopping treatment after sufficient immune restoration has occurred.
HIV therapy - award winning booklet in the information for HIV-positive people series
Viard J-P et al. Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level. AIDS 18: 45 – 49, 2004.