More people would benefit and it would be more cost effective if HIV treatment with antivirals started earlier in countries like South Africa where medical resources are limited, said researchers.

The study was led by investigators from Massachusetts General Hospital (MGH) in the US and the Desmond Tutu HIV Centre at the University of Cape Town and is published in the 4 August issue of the Annals of Internal Medicine. The paper is ready to view online and its release coincides with the International AIDS Society Conference meeting which started in Cape Town on Sunday.

Rapid control of HIV spread is important in any country, but perhaps more so in resource-limited countries with high rates of opportunistic infections, such as South Africa.

However, doctors in South Africa don’t have guidelines about when to start therapy. Part of the reason is because they are waiting for the results of trials to determine how low a patient’s CD4 cell count should be before they start antiretroviral therapy (ART).

CD4 T cells are an important part of the immune system’s defences against disease that is gradually eroded by HIV.

While the decision to start ART is primarily a clinical one, cost-effectiveness is also an important public health consideration.

In the US and other developed countries, ART usually starts when the level of CD4 cells reaches a threshold of 350 cells per microlitre of blood, said the researchers.

However, because ART is expensive and can also have significant side effects, the World Health Organization (WHO) in 2006 recommended a threshold of 200 CD4 cells per microlitre of blood is reached before starting ART, or until the patient develops AIDS-related complications.

Lead investigator Dr Rochelle Walensky, of the MGH Division of Infectious Disease, and associate professor of Medicine at Harvard Medical School, told the press that:

“While those standards accommodate the limited resources and short supply of medications in many settings, the greater prevalence of tuberculosis and other opportunistic infections in places like South Africa argue for earlier treatment initiation, even before the results of ongoing clinical trials are known.”

The trials that everyone is waiting for won’t be finished for several years. But countries like South Africa need guidelines today, said the researchers, which is why they decided to investigate the clinical benefits and cost implications of using the 350 threshold compared with one of 250 cells per microlitre of blood and no treatment.

Walensky and colleagues developed a mathematical model to simulate HIV treatment and its associated health and economic outcomes.

Using the model they worked out the additional costs of earlier treatment, its potential toxicities and its benefits, including TB prevention.

They also calculated how much delaying treatment would shorten patients’ lives and they estimated the cost per extra year of life gained by starting ART earlier. This is a standard way of measuring cost-effectiveness.

The results showed that compared to a threshold of 250, starting ART when the CD4 cell count falls to 350 cells per microlitre of blood is highly cost-effective, even if the chances that a trial might show its superiority were to be as low as 17 per cent.

The researchers said that raising the threshold to 350 cells per microlitre of blood would prevent nearly 76,000 deaths and 66,000 opportunistic infections over the next five years. The cost of doing this would be about 1,200 dollars per year of life saved, they said.

Co-author Robin Wood, director of the Desmond Tutu HIV Centre at the Institute of Infectious Diseases and Molecular Medicine at the University of Cape Town, a leading HIV clinical research group in South Africa, said:

“The time has come to act on the information we now have, nearly all of which supports starting treatment earlier.”

“We can re-evaluate the situation after the trials, but until those results are available, the evidence points to saving lives with earlier treatment,” he added.

“When to Start Antiretroviral Therapy in Resource-Limited Settings.”
R. P. Walensky, L. L. Wolf, R. Wood, M. O. Fofana, K. A. Freedberg, N. A. Martinson, A. D. Paltiel, X. Anglaret, M. C. Weinstein, E. Losina and for the CEPAC-International Investigators.
Annals of Internal Medicine, 2009, 60520-138.
Volume 151, Issue 3, 4 August 2009.

Source: Massachusetts General Hospital.

Written by: Catharine Paddock, PhD