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Do Not Pass Go: Initiating Rapid ART in European Patients With HIV

Chloe Orkin Photo
Chloe Orkin, MBChB, FRCP, MD

Professor of HIV
Queen Mary, University of London
Consultant Physician
Lead for HIV Research
Barts Health NHS Trust
The Royal London Hospital
London, United Kingdom


Chloe Orkin, MBChB, FRCP, MD: consultant/advisor/speaker: Gilead, Janssen, MSD, ViiV; researcher: Gilead, Janssen, MSD, ViiV.


View ClinicalThoughts from this Author

Released: August 19, 2022

Key Takeaways

  • Rapid ART initiation should be offered to all patients after HIV diagnosis is confirmed and clinical assessment has occurred
  • Rapid ART improves engagement in care, time to first appointment, and time to viral suppression

In London where I practice, rapid initiation of antiretroviral therapy (ART) is a common approach to therapy initiation for most patients newly diagnosed with HIV. This approach is widespread because the international HIV treatment guidelines are in agreement: The United States Department of Health and Human Services (DHHS) advise to initiate ART immediately or as soon as possible after diagnosis. The International Antiviral Society (IAS)-USA guidelines suggest starting ART as soon as possible, including immediately after HIV diagnosis if the newly diagnosed person is ready. The European AIDS Clinical Society guidelines adopt a more nuanced approach in deciding whether rapid or same-day ART treatment is advised, suggesting it depends on the setting, circumstances, medical indications, and risk of losing the person from care. Finally, the World Health Organization recommends that rapid ART initiation should be offered to all people following a confirmed HIV diagnosis and clinical assessment.

Regarding first-line regimens, guidelines again agree, and they rely predominantly on first-generation and second-generation integrase inhibitors (INSTIs)—with nucleos(t)ide reverse transcriptase inhibitors.

Rapid ART Treatment Studies
Three clinical trials support our use of rapid initiation of ART:

IMEA-055 FAST study: bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF)
STAT study: dolutegravir/lamivudine
DIAMOND study: darunavir (DRV)/cobicistat + TAF/FTC 

These were all prospective, multisite, single-arm studies that included persons with newly diagnosed HIV and no previous treatment. In each study, treatment was initiated with the first dose within 24 hours to 15 days of the baseline visit and could be initiated before lab results were available. The primary endpoint was HIV-1 RNA <50 copies/mL at either 24 or 48 weeks.
 
The studies recruited young people (median age: 28-36 years). The study populations were almost exclusively male and the median HIV-1 RNA at baseline was approximately 4.7 log10 copies/mL. These studies included patients with high baseline HIV-1 RNA levels. Approximately 40% of participants in FAST and STAT and 25% of those in DIAMOND had high baseline HIV-1 RNA measurements that were >100,000 copies/mL. In other first-line treatment studies, approximately 15% to 20% had baseline HIV-1 RNA measurements >100,000 copies/mL.
 
At the Week 24 primary endpoint analysis of the FAST study, approximately 80% of people had HIV-1 RNA <50 copies/mL. There was a high level of response, even among those with high baseline viral load. There was no treatment-emergent resistance through Week 24 and rates of adverse events were low.
 
The Week 48 primary endpoint analysis of the STAT study showed 97% of people with HIV-1 RNA <50 copies/mL in the observed analysis. There were similar outcomes regardless of baseline viral load. There were no treatment-emergent resistant mutations and no grade 3-5 drug-related events.
 
At Week 48 of the DIAMOND study, there were similar outcomes to the other 2 studies, with 84% of participants achieving HIV-1 RNA <50 copies/mL. There were good outcomes regardless of baseline viral load.  No one met the criteria for protocol-defined virologic failure or resistance testing and there were very low rates of adverse events. 
 
Transmitted Resistance
Should we have concerns about transmitted resistance in rapid initiation first-line ART? We know from the original first-line trials that it is highly unusual for second-generation INSTIs to select for resistance in first-line therapy. Consequently, the DHHS guidelines recommend INSTI resistance testing only if transmitted resistance to INSTIs is a specific concern or if viremia ensues while receiving an INSTI-based regimen.
 
Similarly, the IAS-USA recommend against INSTI resistance testing unless it is suspected that HIV was transmitted from a partner with virologic failure on an INSTI-based regimen.
 
The DHHS guidelines recommend boosted DRV-based regimens for rapid start due to low risk of resistance that has been seen with most boosted protease inhibitors in first-line therapy, even among those with intermittent adherence.
 
Special Populations
The B-HASTE study was undertaken with the premise that adolescents are a population that are easily lost to follow-up after diagnosis. B-HASTE was a small, randomized trial of people with HIV 15 years of age and older who were started on BIC/FTC/TAF within 72 hours of diagnosis or who underwent standard-of-care initiation of ART. We are awaiting results of this study.
 
A systematic review of the rapid ART literature by Ford and colleagues identified 4 randomized clinical trials of ART initiation within 14 days of eligibility compared with standard of care. This review showed that same-day ART initiation increased the likelihood of initiation in the first 90 days, retention, and virologic suppression at 12 months.
 
The RAPID study was one of the first projects in rapid initiation. It was undertaken to try to prevent loss to follow-up in a clinic population in San Francisco. They found that although loss to follow-up was similar, there was a big difference in terms of rapidity of virologic suppression in people with same-day ART initiation compared with historical controls. This cohort involved many people of color, many were substance users, and many were experiencing homelessness. This was a very difficult-to-access group of people, and yet they had very encouraging results.
 
Barriers and Facilitators
My group has done some work at our clinic in East London to try to understand the barriers and facilitators of rapid ART and the needs of people regarding adherence and engagement in care. This is the first qualitative study exploring the acceptability of rapid ART in the United Kingdom.
 
Our findings showed that having a tailored approach that included developing a quality relationship between the person with HIV and the clinical team was key. We also found that providing comprehensive information and peer support in navigating the service was very important.
 
We would like to follow-up these findings by developing strategies to recruit a more gender-diverse sample (ours was predominantly male). Of interest, many of those who did not accept rapid initiation of ART or who stopped rapid treatment were female.
 
Your Thoughts?
What has your experience been with rapid ART initiation? For which patients are you considering this option? What are your concerns? Leave a comment and join the discussion.

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