In the latest issue of the New England Journal of Medicine authors of the Perspective titled “When to Start ART in Africa—An Urgent Research Priority,” call for a randomized, controlled trial to determine when to initiate antiretroviral treatment (ART) in Africa to determine the balance of risks and benefits of early versus delayed treatment.
The researchers Kevin De Cock, MD, DTM&H, CDC Country Director in Kenya, and Wafaa El-Sadr, MD, MPH, director of ICAP at the Columbia University Mailman School of Public Health, argue that definitive research should inform ART initiation guidelines and shed clarity on what is best for the health of people living with HIV.
The question of when to start ART treatment has been debated since the discovery of successful drug therapy. Several groundbreaking trials helped inform ART practices: in the mid- 1990s, the U.S. Department of Health and Human Services recommended that patients with CD4+ count of less than 200 cells per cubic millimeter urgently required ART due to their increased risk for AIDS-related illnesses and death. Later, a randomized, controlled trial in Haiti showed reduced morbidity and mortality among persons who initiated ART with a CD4+ count of 350 cells per cubic millimeter—this standard has since been adopted by the World Health Organization guidelines.
A more recent study (HPTN 052) demonstrated that early ART initiation reduces transmission of HIV, prompting new U.S. guidelines advocating immediate treatment for anyone living with HIV infection. Thus, the pendulum has swung to a focus on the overall potential preventive benefits of ART rather than on issues of individual benefits and risks of such treatment.
However, according to Drs. De Cock and El-Sadr, the latest guidelines are a cause for concern over when to treat, especially for individuals living in low-resource countries with increased exposure to co-morbidities and weak health systems. At least two-thirds of people living with HIV infection are in sub-Saharan Africa and are at greater risk for infections such as tuberculosis, which has increased by a factor of 5 to 10 in sub-Saharan Africa since the beginning of the AIDS epidemic. Mathematical modeling has shown that early initiation of treatment could not only help to prevent tuberculosis in HIV-infected individuals, but could also have a large-scale effect on preventing HIV transmission.
“Uncertainty about ART is detrimental to the millions of people living with HIV infection. Early ART and deferred ART, each recommended and practiced depending on the setting, cannot both be the most favorable choice for individual health,” writes De Cock and El-Sadr.
The authors propose a large, simple trial to assess the risks and benefits of immediate ART versus deferral until a CD4+ count of 350 cells per cubic millimeter is reached. They suggest using ‘easy-to-ascertain’ end points, such as tuberculosis incidence, hospitalization, and death. The results, the authors argue, could lead to a full understanding of the implications of taking ART early or late.