Rapid Antiretroviral Therapy Initiation: New Data and Ongoing Progress in China

Key Takeaways

• In a long-term analysis of the randomized START trial comparing immediate vs delayed ART, the excess risk for serious AIDS event, serious non-AIDS event, or death with delayed ART start substantially decreases after initiation of ART, but that risk still remains, particularly for younger individuals.

Antiretroviral therapy (ART) is a global strategy to optimize the health outcomes of people with HIV (PWH) and to control the HIV epidemic. For many years, the timing of ART initiation for PWH was based on CD4+ cell count or clinical presentation. Then, in 2015, the benefits of universal ART initiation for all PWH regardless of CD4+ cell counts was recognized globally. Several pivotal studies demonstrated that accelerated ART initiation after HIV diagnosis was associated with improved clinical outcomes and reduced the risk of onward HIV transmission. 

At IDWeek 2022, Babiker and colleagues presented the results of a long-term follow-up analysis from the randomized START trial that had previously demonstrated a clear benefit of immediate vs delayed (until CD4+ cell count <350 cells/mm³) ART initiation among PWH who have CD4+ cell counts >500 cells/mm³. The study was stopped in 2015 when the results showed that immediate ART reduced the risk of a serious AIDS event, serious non-AIDS event, or death not attributable to AIDS by 57% compared with deferred ART initiation. At that time, all participants in the deferred ART arm were advised to initiate ART.

This long-term analysis included follow-up from 2016 through 2021 and was aimed at answering the question of whether the excess risk from deferring ART initiation is eliminated once treatment has started and HIV-1 RNA is suppressed.

The investigators found that the excess risk substantially decreases soon after initiation of ART but that some risk still remained, particularly for younger individuals. The HRs for the composite endpoint of serious AIDS event, serious non-AIDS event, or death with immediate vs deferred ART were 0.47 (95% CI: 0.34-0.65) pre-2016; 0.79 (95% CI: 0.60-1.04) post January 1, 2016; and 0.61 (95% CI: 0.49-0.76) for the entire period from randomization through 2021.

Among those aged 35 years or younger, the HR for the post January 1, 2016, period was 0.42 (95% CI: 0.24-0.71).

Overall, the long-term analysis reinforces the original finding that early diagnosis and treatment provide significant benefit to PWH. 

Rapid ART Trends
Today, there is global consensus that, for all PWH, it is preferred to take an even faster approach, termed “rapid ART initiation” and defined as starting ART as soon as possible after diagnosis, including the same day as diagnosis. Sufficient studies have proven the benefits of rapid ART initiation after HIV diagnosis. 

According to convention, patients diagnosed with HIV infection for the first time often require long waits or multiple clinic visits before they receive ART. In recent years, a series of studies has been conducted to verify the effects of same-day ART in different settings. Using an intervention to provide increased knowledge of the long-term benefits of ART, a study in Haiti showed that PWH in the same-day ART group were more likely to initiate ART rapidly and had a higher rate of retention in care vs the standard ART initiation group (80% vs 72%). However, another study in Swaziland observed that PWH who initiated ART on the same day as diagnosis may be at a higher risk of loss to follow-up. 

Rapid ART in China
In China, several studies also have provided evidence in support of rapid ART initiation. A national cohort study showed that ART initiation within 30 days of HIV diagnosis significantly reduced the risk of drop out and treatment failure. Even among PWH with CD4+ cell counts >500 cells/mm³, the national cohort study also showed that initiating ART within 30 days reduced the risk of death by 63%. 

To quicken ART initiation among PWH, the Chinese Free Antiretroviral Therapy Program has taken a series of measures. First, the standard eligibility for ART initiation was revised in 2016 such that ART initiation is now recommended for all newly diagnosed PWH regardless of their CD4+ cell count. As early as 2012, a pilot study was conducted in 2 counties to simplify the process by providing rapid HIV diagnosis and treatment services. Using the simplified approach, the time to ART initiation for newly diagnosed PWH was reduced to 5 days, and mortality was reduced by 62%. This strategy of simplifying the process from diagnosis to treatment was subsequently promoted in other regions of the country. Another cluster randomized controlled trial showed that the “One4All” strategy, including rapid, point-of-care HIV screening and CD4+ cell count with concurrent HIV-1 RNA testing, greatly improved the uptake of ART and reduced mortality by more than one half. 

In 2021, two thirds of newly diagnosed PWH nationwide began ART within 30 days of diagnosis, and the median time from diagnosis to ART initiation was shortened to 14 days. But rapid ART initiation still faces some challenges. The burden of the HIV epidemic and medical resource availability vary greatly across different regions. PWH who have opportunistic infections often require time to begin treatment for the opportunistic infection before initiating ART. Further study of strategies to address the issue of how to accelerate ART initiation is still needed.

Your Thoughts?
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