A major clinical trial has shown that HIV-positive patients in resource limited countries are more likely to survive and experience less HIV disease progression if they start taking antiretroviral therapy when their CD4 cell count is between 350 and 200 cells/mm3, rather than waiting until their CD4 cell count falls to below 200 cells/mm3.
Interim analysis of the CIPRA HT 001 study, a randomised control trial being conducted in Haiti, showed that patients who started HIV treatment before their immune system had been severely damaged had better outcomes.
A total of 816 adults with CD4 cell counts between 300 and 250 were recruited to the study. Half were randomised to start HIV treatment immediately, the others waiting until their immune systems had weakened further or they developed an AIDS-defining illness. The combination of antiretroviral drugs used in the study was efavirenz, 3TC and AZT.
The study’s independent safety and monitoring board recommended that the trial should be stopped early after a planned interim analysis showed that only six patients who started antiretroviral therapy when their CD4 cell count was between 350 – 200 cells/mm3 died. (Patient recruitment began in 2005 but the median duration of follow-up is unspecified in the NIAID press release).
This compared to 23 deaths amongst individuals who started treatment later. Furthermore, twice as many individuals in the deferred treatment arm of the study developed tuberculosis, an AIDS-defining illness, than did patients who started HIV treatment before their immune systems were severely damaged by the virus.
In the light of these findings, the study’s monitoring board recommended that it should be terminated immediately and that all individuals in the deferred treatment arm should be offered anti-HIV drugs.
HIV treatment guidelines in industrialised countries, such as the UK, recommend that HIV treatment should be started when an individual’s CD4 cell count is around 350 cells/mm3. Starting treatment at this time has been shown to reduce the risk of developing both HIV-related and non-HIV-related illnesses.
However, in resource limited settings, where only 30% of eligible individuals are currently taking anti-HIV drugs, treatment is not started until a patient’s CD4 cell count falls below 200 cells/mm3 or they develop AIDS. HIV treatment is often started by individuals when their immune systems are severely weakened, meaning that in many cases they die before they have the opportunity to benefit from HIV treatment.
“The public health community now has evidence from a randomized, controlled clinical trial – the gold standard – that starting antiretroviral therapy between 200 and 350 cells/mm3 in resource-limited settings yields better health outcomes than deferring treatment”, said Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, who sponsored the study.