Since 1996 the availability of highly active antiretroviral therapy (HAART) in North America and Western Europe has helped reduced death rates from AIDS-related complications. Once the benefit of HAART became apparent, doctors were initially aggressive in prescribing it, even for their patients who had relatively high CD4+ T-cell counts. With the passage of time, however, it has become clear that HAART has limitations, including the following:
As a result, doctors and their patients are increasingly delaying therapy and treatment guidelines have been revised. Yet the important question "When is the best time to start therapy?" has not been answered and is something with which doctors and people with HIV/AIDS (PHAs) struggle. Recently, results from two large studies that can help decision-making when it comes to the issue of starting therapy have become available in the Journal of the American Medical Association (JAMA). In these studies, researchers examined the effect of starting HAART in PHAs at different stages of HIV disease who had not previously used anti-HIV drugs. In the first study, conducted in Europe with about 3,000 subjects, researchers were trying to find out if PHAs with a high viral load were less likely to achieve a suppressed viral load (fewer than 500 copies) than PHAs who started therapy with relatively low viral loads. In analysing the data, the researchers found that having a high viral load or low CD4+ cell count were not barriers to a PHA's ability to achieve a suppressed viral load while taking HAART.
A second study, conducted in British Columbia, confirmed and extended the above findings. In this Canadian study, researchers collected data on more than 1,200 subjects who started taking HAART. Tracking the subjects over a two-year period, the researchers found that those who started therapy with 200 or more CD4+ cells had a relatively low risk of developing AIDS or dying compared to subjects who started therapy with fewer CD4+ cells. Based on the results of these two large studies, an editorial suggested the following general points:
Of course, these two points are general statements. Readers should note that in some PHAs the decline in CD4+ cell counts may be rapid. Frequent monitoring of these PHAs may help their doctors decide when to begin therapy before the CD4+ count falls below the 200 cell mark. Overall, the results of these two studies act as a guide for clinical decision-making.
In this issue of TreatmentUpdate, we review data from these two studies, focusing on the impact of therapy initiated at different stages of HIV disease. In particular, we will be looking at the data on survival.
REFERENCES
1. Pomerantz RJ. Initiating antiretroviral therapy during HIV infection: confusion and clarity. JAMA2001;286(20):2597-2599.
2. Michael CG, Kirk O, Mathiesen L and Nielsen SD. The naïve CD4+ count in HIV-1-infected patients at the time of initiation of highly active antiretroviral therapy is strongly associated with the level of immunological recovery. Scandinavian Journal of Infectious Diseases2002; (in press).
3. 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. JAMA2001;286(20):2560-2567.
4. Hogg RS, Yip B, Chan KJ, et al. Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA2001;286(20):2568-2577.
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