Starting antiretroviral therapy (ART) in HIV patients with relatively high CD4+ counts but no signs of disease may lead to better outcomes. Two studies in the New England Journal of Medicine (NEJM) support this growing trend in HIV treatment.
Although it’s helped reduce death and disease related to acquired immunodeficiency syndrome (AIDS) around the world, questions remain over the timing of beginning ART in asymptomatic patients, observed Salim S. Abdool Karim, M.B., Ch.B., Ph.D., in an NEJM editorial that discusses the findings of the two studies. “Initial calls to ‘hit HIV early and hard’ two decades ago were countered by the pragmatic prioritization of patients at highest risk for AIDS — namely, those with low CD4+ cell counts (≤200 cells per cubic millimeter),” he wrote. However, with the emergence of new clinical trial data, the threshold for beginning ART has steadily risen over the years, eventually reaching 500 cells per cubic millimeter.
The two studies, the Strategic Timing of Antiretroviral Treatment (START) study and TEMPRANO ANRS 12136 study, further support the concept of treating asymptomatic patients at this higher CD4+ cell count, Karim indicated.
For the START study, researchers drew from a pool of 4,685 HIV-positive adult patients at 215 sites in 35 countries, dividing them into two study groups. In one cohort, patients with CD4+ cell counts at 500 cells per cubic millimeter immediately began ART; in the other, treatment was deferred until counts dropped to 350 cells per cubic millimeter.
After following the patients for 3 years, the researchers determined that those in the immediate initiation group were 72% less likely to have an AIDS-related event, nearly 40% less likely to have a serious non-AIDS related event, and more than 40% less likely to die from any cause.
The TEMPRANO study involved 2,056 HIV type 1 infection patients in Ivory Coast who had CD4+ counts of <800 cells per cubic millimeter. Per World Health Organization (WHO) guidelines, none of these patients had met criteria for beginning ART. Researchers divided these participants by random selection into the following treatment groups: deferred ART (ART initiation according to WHO criteria); deferred ART plus 6-month isoniazid preventive therapy (IPT); early ART; or early ART plus IPT.
More than 40% of these participants had a baseline CD4+ count of ≥500 cells per cubic millimeter.
Researchers found that “immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter,” according to a summary of the TEMPRANO findings in the NEJM article.
For those with a baseline CD4+ count of ≥500 cells per cubic millimeter, the risk of death or severe HIV-related illness was 44% lower in the early ART groups than in the deferred ART groups, and 39% lower in the IPT groups versus those patients who hadn’t received IPT.
Overall, “patients initiating ART early in the START and TEMPRANO trials had viral suppression rates exceeding 95% and 80%, respectively,” Karim noted in his editorial on the findings. The impact of early ART interventions in reducing tuberculosis cases in both trials was an especially important finding. As the article on the TEMPRANO trial points out, tuberculosis and other diseases are fairly prevalent among patients with HIV in low-resource nations.
Another key takeaway is the fact that no significant adverse events resulted from patients getting early treatment with ART, Karim added. In his view, this lays to rest “misplaced concerns that early ART initiation may be harmful, especially owing to tenofovir-related renal concerns and efavirenz-related mental health concerns.”
The challenge is finding the resources to convert these trial results into global HIV treatment programs, Karim noted in his editorial. “Although several countries have made generous contributions for AIDS treatment and prevention programs, the need for additional donations to the hardest-hit poor countries comes at a time when international funding for AIDS is not as readily available,” he indicated.