"Virologic failure, low-level viremia, and viral blip after HIV RNA suppression"
Failure to reach an undetectable viral load in the first year of antiretroviral therapy (ART) led to nearly a 10-fold higher risk of subsequent virologic failure in a 17,000-person North American analysis . Taking more than 1 year to control HIV did not confer a higher risk of low-level viremia or viral blips in this 6-year study.
Reaching and maintaining an undetectable viral load are essential to successful ART. But people with differing HIV disease characteristics taking different antiretroviral regimens with differing adherence vary in the time to an undetectable load. Researchers working with the NA-ACCORD cohort conducted this study to see whether time to undetectability affects rates of virologic failure, low-level viremia, or viral blips.
People in this analysis had to be enrolled in an NA-ACCORD cohort and to begin combination ART between January 2006 and December 2015. The analysis excluded people with previous antiretroviral prescriptions or with a viral load below 1000 copies. Everyone reached an undetectable load, defined as two consecutive loads at or below 50 copies.
Researchers divided time to viral suppression into three groups: 6 or fewer months, between 6 and 12 months, or more than 12 months. They defined virologic failure as two consecutive viral loads at or above 200 copies, low-level viremia as two consecutive loads of 51 to 199 copies, and viral blips as one viral load of 51 to 199 copies immediately preceded and followed by a sub-50 load. Follow-up began when a person reached an undetectable load and continued for up to 6 years.
The analysis included 16,994 people, 34% of whom had an undetectable viral load in the first 6 months of ART, 40% of whom reached undetectability in 6 to 12 months, and 26% of whom took more than 12 months. Median ages of these three groups were similar (40, 41, and 43 years), as were proportions of men (82%, 84%, and 82%). The under-6-month, 6-to-12-month, and over-12-month groups differed in proportions of blacks (35%, 36%, and 43%) and proportions of drug injectors (13%, 13%, and 18%). Median year when ART began stood at 2011 in all three groups, but median pre-ART viral load differed across the three groups (28,000, 62,457, and 82,713 copies), as did proportions starting with an integrase inhibitor (31%, 16%, and 13%), proportions with an AIDS diagnosis (12%, 14%, and 20%), and proportions with HCV infection (10%, 9%, and 15%).
In an analysis weighted over 6 years, virologic failure was less frequent in the under-6-month group (10.5%) and the 6-to-12-month group (10.8%) than in the over-12-month group (20.3%). Compared with the under-6-month group, the over-12-month group had almost a 10-fold higher risk of virologic failure (risk difference 9.84, 95% confidence interval 5.08 to 19.5) in an analysis accounting for numerous demographic and HIV-related variables. Similar analyses found little risk difference between these two groups in low-level viremia or viral blips.
The NA-ACCORD team noted that their analysis may be biased by limited integrase inhibitor data, lack of ART adherence measures, varying intervals between clinic visits or viral load measures, and other unmeasured confounders. With these caveats in mind, they proposed that "patients observed to take longer than one year to achieve viral suppression after initiating ART may experience increased risk of subsequent virologic failure." They suggested that optimal treatment may require identifying and removing barriers to rapid viral suppression with ART.
1. Lee JS, Althoff KN, Humes E, et al. Virologic failure, low-level viremia, and viral blip after HIV RNA suppression. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 97.