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Each Delayed Month in Starting ART Could Trim CD4 Tallies Substantially
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
Delaying antiretroviral therapy (ART) for 1 month from the day of infection cuts the number of CD4 cells a person can gain by 5 to 8 cells, depending on whether that person interrupts therapy during that year [1]. This modeling study determined that, over the course of a single year, continued foot dragging in starting ART could yield a clinically meaningful decrement in potentially gained CD4s.
This analysis of the Acute Infection Early Disease Research Program (AIEDRP) includes 1696 people with a closely estimated date of HIV infection. They enrolled during acute or early infection, and 60% began ART within 12 months of the estimated date of infection. About two thirds of people (67%) were white, 4.5% were women, and 4% were injection drug users. Most people starting ART had reasonably high CD4 counts when they began therapy (interquartile range 317 to 594).
The investigators considered people who began ART within 1 year of their estimated date of infection by two methods: ignoring ART interruptions and eliminating people after they interrupted ART more than 21 days. They used "doubly robust" Coarse Structural Nested Means Models [2] to account for baseline and time-varying confounders that might cause selection bias (ART begun sooner for sicker people with lower CD4 counts).
Modeling the expected CD4 gain during 1 year of ART as a linear function of time from estimated date of infection to the first day of ART, the researchers found a decided benefit to starting ART earlier. They estimated that 1453 people starting ART on their day of infection would gain 317 CD4 cells in the first year of treatment (95% confidence interval [CI] 262 to 359), if people did not interrupt therapy. Each month of delay in starting ART made a difference, slicing 7.6 CD4s off the tally (95% CI -14 to -0.4). A monthly decrement of 7.6 CD4s may not sound like much, but over the course of a year continued delay would add up to 91.2 fewer CD4 cells gained in the first year of therapy, which would easily have clinical significance. Even delaying ART for 6 months would chop 45.6 CD4s off of the first-year total.
In a model considering 1696 cohort members, 243 of whom interrupted ART, people would gain an estimated 311 CD4 cells in the first year of treatment if they started ART on the day of infection. Every month of delay in starting ART cut that total by 5 CD4 cells (95% CI -12 to 0.5). If the delay stretches to 1 year, that decrement adds up to 60 CD4 cells lost during the first year of therapy, a possibly clinically significant difference.
In some jurisdictions, health authorities have deployed strategies to begin ART immediately after a person tests positive, on the same day, if possible [3]. Data like those from this modeling study support the validity of that approach.
References
1. Yang S, Little SJ, Smith DM, DeGruttola V, Lok J. Impact of each month delay in initiation on the effect of 1 year of ART on CD4 count. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 942.
2. Lok JJ, DeGruttola V. Impact of time to start treatment following infection with application to initiating HAART in HIV-positive patients. Biometrics. 2012;68:745-754. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811162/
3. McNeil DG Jr. San Francisco is changing the face of AIDS treatment. New York Times. October 5, 2015.
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