Early use of antiretroviral treatment improves survival rate of HIV patients

May 17 2009

A clinical study, led by researchers from University College Dublin, Ireland, and Stanford University, California, USA, with international collaborators, demonstrates that mortality rates of HIV patients can be almost halved when early antiretroviral (ARV) therapy is added to the treatment of AIDS-related opportunistic infections (OIs) such as pneumonia, meningitis or other serious bacterial infections.

The researchers are part of the AIDS Clinical Trials Group, the world's largest clinical trial organisation, and their scientific findings, published in PLosONE, recommend changes in the treatment regimes for HIV patients worldwide.

A growing number of AIDS patients in Europe and the US are being diagnosed late in the disease process, when they have already contracted life-threatening conditions. When these patients come for treatment of these complications, doctors are often reluctant to give them anti-AIDS drugs at the same time, fearing the two therapies could interfere with one another.

"A lot of doctors wait, thinking, 'Let's get the patient out of acute crisis, and then we'll deal with (the underlying HIV infection) later,'" said Andrew Zolopa, associate professor of medicine at Stanford University School of Medicine and first author of the study. "But that answer is wrong. If we're more aggressive with HIV drugs, we can reduce AIDS-related complications and death by 50 percent. It's a substantial patient benefit."

Professor William Powderly, MD, dean of medicine at the University College Dublin School of Medicine, and the study's senior author, said the research addresses one of the last, longstanding unknowns in the management of AIDS. "Clinicians have long grappled with the question of whether or not early treatment with antiviral drugs will help people who come to the hospital with advanced infections, such as pneumonia."

"The answer is clearly yes. Early antiretroviral treatment for HIV improves the clinical outcome, including the likelihood of surviving in the next few months. It probably does so by rapidly improving the immune system and therefore adds to the ability to resist these infections."

The study could have widespread impact as an increasing number of patients in the United States and Europe, particularly injection drug users and migrants from resource-poor countries, are being first diagnosed with HIV when their disease is well-advanced, Powderly said.

"This study shows that it is life-saving to treat those persons with antiretroviral drugs while they are still in the hospital. The results of this study will change practices throughout the world."

The findings, presented in abstract form at an earlier scientific meeting, are already starting to change clinical practices. The International AIDS Society, the Center for Disease Control in the US and the British AIDS Society all have adopted guidelines that recommend that early antiretroviral treatment be considered in patients with an opportunistic infection.

The study, conducted by the AIDS Clinical Trials Group, involved 262 patients at 39 sites stretching across the United States. An additional 20 patients were enrolled in Johannesburg, South Africa. Eighty-five percent of the patients were men whose median age was 28. They were an ethnically diverse group: 37 percent were black, 36 percent Hispanic, 23 percent white and 5 percent Asian.

The patients all had one or more opportunistic infection, with the most common ones being pneumocystis jirovecii pneumonia, cryptococcal meningitis and serious bacterial infections. Patients with tuberculosis were excluded from the study because it was unclear what the optimal antiviral treatment was for these patients.

The patients, who were enrolled between May 2003 and August 2006, were separated into two groups: those who got antiretroviral treatment early and those for whom this treatment was delayed until their opportunistic infections had been dealt with. The patients were all offered antiretroviral drugs free of charge. The drugs for the study were supplied by Abbott Laboratories (lopinavir/ritonavir) and Gilead Sciences (tenafovir and emtricitabine).

The patients in the early arm of the study were treated with ARVs within an average of 12 days, while those in the deferred group received the treatment within an average of 45 days. Among the patients treated early, there were 20 (14.2 percent) who died or developed a significant AIDS-related complication. That compared to 34 patients (24.1 percent) in the deferred group who died or suffered a new complication.

In addition, the patients in the early group saw a much swifter recovery of their immune systems. The early group patients saw their T-cell counts, a measure of the immune cells destroyed by the AIDS virus, increase to more than 100 within four weeks. In the deferred treatment group, it took 12 weeks for the patients' T-cells to reach that same level, the researchers reported.

"I was quite impressed at how rapidly these T-cells could rise in these patients," Zolopa said. "By starting ARV therapy early you can effectively reduce the window of vulnerability where another AIDS-related complication could develop."

He said the study results probably provide some guidance for patients in developing countries, though each country would have to determine its own strategy for initiating ARVs in patients with advanced AIDS.

"Although the study did not include patients with TB, the most common AIDS-related complication among patients in sub-Saharan Africa, early treatment has been shown in other, more recent studies to be of value in those patients with TB," Powderly said. "These results have important implications across the globe."

The study was funded by the US National Institutes of Health through the Division of AIDS.