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Viral Rebound No Slower When Stopping Modern ART Combinations
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AIDS 2020: 23rd International AIDS Conference Virtual, July 6-10, 2020
Mark Mascolini
Contemporary antiretroviral therapy (ART) regimens did not prolong time to viral rebound after treatment interruption when compared with historical ART combinations in an AIDS Clinical Trials Group (ACTG) analysis [1]. But starting ART early (Fiebig stages III-V) rather than more than 6 months after infection did significantly boost the percentage of people who remained off treatment for more than 12 weeks.
ACTG protocol A5345 prospectively studies ART treatment interruptions to chart rebound dynamics of contemporary regimens and to identify predictors of HIV rebound timing. The study considers two groups starting ART: a chronic group who began ART more than 6 months after their date of infection, and an early group who began ART during HIV infection Fiebig stages III-V. For both groups the researchers selected historic controls from non-NNRTI arms in six older ACTG treatment interruption trials.
All participants were between 18 and 70 years old and had a treatment-induced viral load below the limit of detection for at least 24 months. Everyone had a current CD4 count of 500 or higher, a nadir CD4 count of 200 or higher, and no history of an AIDS illness.
Participants received close monitoring after treatment interruption. They resumed ART if they had (1) two consecutive viral loads at or above 1000 copies, (2) a single load at or above 1000 copies and an average daily viral load rise of at least 0.5 log10 copies/mL, (3) a single viral load at or above 10,000 copies, (4) a CD4 count below 250 or a count less than 50% of the entry CD4 count, (5) clinical progression to CDC category B or C disease or diagnosis of acute retroviral syndrome, or (6) patient or provider request to resume ART.
The study population included 33 people in the chronic group, 61 historic chronic controls, 12 in the early group, and 74 historic early controls. Median ages of those four groups were 46, 43, 38, and 37, and proportions of men 88%, 87%, 100%, and 95%. In the A5345 chronic group proportions of whites were 73%, blacks 12%, and Hispanics 12%, and in the A5345 early group proportions were 8% white, 33% Hispanic, and 50% Asian. Initial pre-ART viral loads were 4.5 log10 copies/mL in the chronic group, 4.4 in chronic controls, 5.7 in the early group, and 4.7 in early controls.
Time to viral load at or above 1000 copies did not differ significantly-or much at all-between either the chronic or early A5345 arms or their historic control groups. By interruption week 12, 80% or more of each group had lost viral suppression. One person in the early group and one in the chronic group stayed off ART for at least 24 weeks, though the person in the chronic group had a pre-ART viral load below 1000 copies.
Compared with chronic A5345 participants, early participants had a modest (about 2-week) delay in viral rebound. In a pooled analysis of A5345 participants and historic controls, a significantly higher proportion of early-treated people than chronic participants remained off ART for more than 12 weeks (10% versus 2%, P = 0.03). During treatment interruptions, CD4 counts dropped about twice as much at interruption weeks 2 and 4 in chronic-treated participants than in early-treated people (down about 140 versus 70 CD4s at week 4).
The ACTG team discerned no significant association between ART duration or CD4 count and timing of viral rebound. Statistical analysis suggested that higher pre-ART viral load predicted a shorter time to rebound in chronic-treated people (Spearman r = -0.37, P = 0.09) but not in the early group (r = 0.30, P = 0.34). While 9% of the chronic group experienced the acute retroviral syndrome, none of the early group did. All participants regained viral control when they restarted ART.
Ongoing analyses are assessing biomarker predictors of HIV rebound after treatment interruption.
Reference
1. Li JZ, Aga E, Bosch R, et al. Time to viral rebound after interruption of modern antiretroviral therapies. AIDS 2020: 23rd International AIDS Conference Virtual. July 6-10, 2020. Abstract PDB0102.
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