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Large study proves that HAART reduces rates of AIDS and death
Chris Gadd, Friday, August 12, 2005
Use of highly active antiretroviral therapy (HAART) in HIV-positive patients reduces the risk of developing AIDS or death by 86% compared with no treatment, according to a large analysis of data from the Swiss HIV Cohort Study. The results were published in the 30th July edition of The Lancet.

The benefits of HAART in reducing HIV viral loads and increasing CD4 cell counts are well established. However, few studies have proved that improvements in these ‘surrogate endpoints’ are linked to reduced rates of AIDS or death. This is because most investigations are restricted to one or two years’ follow-up, whereas HAART is usually taken for longer periods. In addition, a randomised trial comparing HAART to no HIV treatment has never been attempted on ethical grounds.

The investigators adjusted their analysis according to changes in the patients’ CD4 cell counts and viral loads over time, using a new statistical method. This enabled the risk of AIDS or death to be calculated independently of CD4 cell count and viral load. Failure to do this would have made their results unreliable, as these values are used to decide when to start treatment but are also affected by antiretroviral therapy.

In order to demonstrate that taking HAART is linked to improved AIDS and death rates, investigators analysed data collected from 3245 HIV-positive patients, who had been examined at least once after the introduction of HAART in Switzerland in January 1996. At the start of the study, each patient was free of AIDS and not taking HAART, defined as “a combination of at least three drugs, typically including either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor, and two nucleoside reverse transcriptase inhibitors (NRTIs).”

Overall, the investigators found that taking HAART reduced the risk of developing AIDS or death by 86% (95% confidence interval [CI]: 61 – 93%), compared to no treatment. AIDS was defined according to the 1993 Centers for Disease Control and Prevention (CDC) stage ‘C’ criteria.

Compared to taking antiretroviral therapy consisting of two NRTIs, HAART reduced the risk of death by 51% (95% CI: 21 – 69%).

With increasing time on HAART, the difference between patients taking HAART and not on treatment became more pronounced, rising to a 96% (95% CI: 91 – 99%) difference after two years. This indicates “persistently low progression rates with HAART but increasing progression rates for patients who remained untreated,” the investigators explain.

They observed a similar trend when they compared patients taking HAART to those on dual drug therapy.

In contrast, however, there was no increased benefit of HAART seen over calendar time. “The increasing experience of treating physicians and the availability of new drugs might have been counterbalanced by adverse factors such as increasing prevalence of strains that are resistant to common drugs or by evolutionary changes in virulence of HIV,” the researchers explain. “Clearly, it will be important to monitor trends in the effectiveness of HAART in coming years.”

The investigators also found that HAART was less beneficial for patients infected through intravenous drug use than for other patients (73 vs. 92%; p = 0.01). They speculate that this may be due to worse adherence in this group, an increased risk of death from drug overdose or violence or the increased chance of hepatitis C co-infection.

Neither age nor gender altered the effectiveness of HAART.

Unsurprisingly, the study showed that lower CD4 cell counts (p < 0.001) and higher viral loads (p < 0.001) were associated with an increased likelihood of patients starting HAART. It was also linked to the change in these values over the last three months and the occurrence of HIV-related illnesses. In contrast, patients infected through intravenous drug use were less likely to start treatment that other groups.

One limitation of this study is that it assumes that treated and untreated patients with the same routes of HIV infection, CD4 cell counts, viral loads and HIV-related symptoms are similar. “Prospective information about the reasons that patients remain untreated is not recorded in the database, so we cannot address this issue directly,” the investigators write.

Reference

Sterne JAC et al. Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study. Lancet 366: 378-384, 2005.