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High HIV Control Rate With Rapid D/C/F/TAF in Newly Diagnosed
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IDWeek, October 2-6, 2019, Washington, DC
Mark Mascolini
Through 48 weeks of treatment with single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in 109 people with newly diagnosed HIV, no one stopped treatment for lack of efficacy or met protocol-defined virologic failure criteria [1]. In an analysis excluding missing data, all DIAMOND trial participants had a viral load below 200 copies at week 48.
Research shows that rapidly starting antiretroviral therapy in people with newly diagnosed HIV infection shortens time to an undetectable viral load, improves retention in care, and lowers morbidity and mortality. Some antiretroviral treatment guidelines endorse rapid treatment initiation, although US DHHS experts still consider this approach investigational.
DIAMOND, a phase 3 open-label trial [2], tested the efficacy and safety of single-tablet D/C/F/TAF in people with newly diagnosed HIV infection. People 18 or older were eligible for the trial if they had been diagnosed with HIV within 2 weeks. They got their first dose of D/C/F/TAF within 24 hours of screening, before results of initial safety and resistance lab results were available. The trial defined virologic failure as (1) less than a 1-log (10-fold) drop in viral load and a viral load of 400 copies or higher at week 12, or (2) after consecutive viral loads below 50 copies, a rebound above 50 copies or a 1-log jump in viral load. The primary endpoint was the proportion of participants with a viral load below 50 copies by FDA snapshot analysis at week 48.
The 109 study participants had a median age of 28 (range 19 to 66), 87% were men, 32% black, 68% nonblack, and 44% Hispanic. Three quarters of participants acquired HIV infection during sex between men. Median time from HIV diagnosis to enrollment stood at 5 days (range 0 to 14), and 31% of participants enrolled within 48 hours of diagnosis. Median pretreatment viral load stood at 38,700 copies, and 25% had a viral load above 100,000 copies. Median initial CD4 count measured 369 and ranged from 7 to 1082.
At week 48 the FDA snapshot analysis indicated that 92 of 109 people (84%) had a viral load below 50 copies, while 96 of 109 (88%) were under 200 copies. An observed analysis excluding people with missing data indicated response rates of 96% below 50 copies and 100% below 200 copies. No one quit the study because of lack of efficacy or met virologic failure criteria.
By snapshot and observed analyses, sub-50-copy response rates at week 48 were 89% and 99% among people starting treatment with fewer than 100,000 copies of HIV RNA, and 70% and 86% for those starting above 100,000 copies. Among people starting above 100,000 copies, snapshot and observed analyses determined that 82% and 100% had a week-48 viral load below 200 copies.
By snapshot analysis, week-48 sub-50-copy response rates by days from diagnosis to enrollment were 91% for 0-1, 91% for 1-2, 75% for 2-3, 84% for 3-7, and 79% for 7-14. By observed analysis, proportions below 50 copies at week 48 were 96% for 0-1 days from diagnosis to enrollment, 100% for 1-2 days, 100% for 2-3 days, 94% for 3-7 days, and 96% for 7-14 days.
Ten people (9%) had any serious adverse event, none of them related to study drugs. Thirty-six people (33%) had any drug-related adverse event, 7 (6%) of them grade 2 or worse and 2 (2%) grade 3. There were no grade 4 drug-related adverse events. One person stopped treatment because of drug-related adverse events: grade 3 allergic dermatitis, grade 2 fever, and grade 2 lip swelling. Immune reconstitution inflammatory syndrome (IRIS) emerged in no one, even though 25% of participants had a pretreatment viral load above 100,000 copies and 21% had a pretreatment CD4 count below 200.
DIAMOND investigators concluded that this first phase 3 study of rapid antiretroviral initiation with a single-tablet regimen found high 48-week rates of virologic suppression regardless of time from HIV diagnosis to enrollment, pretreatment viral load, or pretreatment CD4 count.
References
1. Huhn GD, Ramgopal M, Crofoot G, et al. High rates of virologic suppression achieved in HIV-1-infected adults rapidly starting antiretroviral therapy (ART) with the single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg regardless of baseline disease characteristics: week 48 subgroup analyses from the phase 3 DIAMOND trial. IDWeek, October 2-6, 2019, Washington, DC. Abstract 887.
2. ClinicalTrials.gov. A study to evaluate the efficacy and safety of (D/C/F/TAF) once daily fixed dose combination (FDC) regimen in newly diagnosed, antiretroviral treatment-naive human immunodeficiency virus type 1 (HIV-1) infected participants receiving care in a test and treat model of care. ClinicalTrials.gov identifier NCT03227861.
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