Researchers in Western Europe analysed information collected from 3,226 HIV positive subjects, all of whom began therapy with at least three drugs taken in combination. These subjects were monitored for up to three years after they started therapy. Researchers were mainly interested in learning about the ability of therapy to suppress viral load in subjects with different CD4+ T-cell counts. The average profile of subjects at the start of the study was as follows:
Also at the start of the study, researchers divided subjects into three smaller groups based on their CD4+ cell count as follows:
Results— based on CD4+ cell counts
By the 8th month of the study, the proportion of subjects in each of the three CD4+ cell groups with a suppressed viral load (fewer than 500 copies) was as follows:
These differences between the three groups were not statistically significant.
Results— based on viral load
Another way researchers could group subjects was by their viral load at the start of the study. Those subjects who entered the study with relatively high viral loads — at least 100,000 copies — took significantly longer to achieve a suppressed viral load (fewer than 500 copies) than people who started the study with a relatively lower viral load — fewer than 100,000 copies. However, after four months of HAART, differences between the two groups began to grow smaller such that by the 8th month of the study the proportion of subjects in each group who had fewer than 500 copies was similar.
Other factors, such as the sex of the subjects or their having AIDS at the start of the study, had no significant impact on their ability to achieve a suppressed viral load.
The number of deaths that occurred during the study by CD4+ count grouping was as follows:
Adjusting for the number of people in the study and the length of time they were monitored, the researchers calculated that the risk of death for subjects who started therapy when their CD4+ count was below the 200 cell mark was three times greater than for subjects who started therapy with between 200 and 349 CD4+ cells.
Another way researchers analysed the data was to note the numbers of subjects who developed AIDS-related diseases or who died during the study in the following manner:
According to their calculations, the researchers found that subjects who started therapy when their CD4+ count was below the 200 cell mark were at least five times more likely to develop AIDS-related diseases or die compared to subjects who started therapy when their counts were 350 cells or greater. This difference between the two groups was statistically significant; that is, not likely due to chance alone.
Consensus is emerging that PHAs should start HAART before CD4+ counts fall below the 200 cell mark. The study researchers note that "how close to this value the CD4+ cell count should be permitted to [fall]" before therapy is initiated is something over which there is no consensus. Indeed, the timing of therapy for an individual PHA may depend on "the degree of CD4 depletion [doctors and PHAs are] willing to tolerate."
1. In this large study, researchers did not find that viral load responses to HAART were worse in PHAs who had between 200 and 349 CD4+ cells compared with PHAs who had higher cell counts in "either the short-term or long-term."
2. Researchers did not find that viral load responses to HAART were worse in PHAs whose pre-treatment viral load ranged between 10,000 to 100,000 copies and those who had fewer than 10,000 copies.
Among subjects who entered this study with a viral load greater than 100,000 copies, it took longer for their viral load to fall below the 500 copy mark once they began therapy than it did for subjects who had pre-HAART viral loads below the 10,000 copy mark. Nonetheless, by the 8th month of therapy the proportion of subjects with suppressed viral loads was similar regardless of whether pre-study viral loads were high (100,000 copies) or low (fewer than 10,000 copies). As well, similar proportions of subjects experienced virologic failure.
3. Other issues to consider, and not explored in this study, include the following:
Hopefully other studies will investigate these and other issues related to the timing of therapy.
REFERENCE
Phillips AN, Staszewski S, Weber R, et al. HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA 2001;286(20):2560-2567.
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