Predictors of residual viraemia in patients on long-term suppressive antiretroviral therapy
Lu Zheng, Ronald J Bosch, Ellen S Chan, Sarah Read, Mary Kearney, David M Margolis, John W Mellors, Joseph J Eron, Rajesh T Gandhi, DS Clinical Trials Group (ACTG) A5244 Team, Lu Zheng, Ronald J Bosch, Ellen S Chan, Sarah Read, Mary Kearney, David M Margolis, John W Mellors, Joseph J Eron, Rajesh T Gandhi, DS Clinical Trials Group (ACTG) A5244 Team
Abstract
Background: HIV-1-infected individuals with plasma RNA<50 copies/ml on antiretroviral therapy (ART) may have residual, low-level viraemia detectable by PCR assays that are able to detect a single copy of viral RNA (single-copy assay [SCA]). The clinical predictors of residual viraemia in patients on long-term suppressive ART are not yet fully understood.
Methods: We evaluated factors associated with residual viraemia in patients on suppressive ART who underwent screening for a raltegravir intensification trial (ACTG A5244). The screened population was HIV-1-infected adults receiving ART for ≥ 12 months with pre-ART HIV-1 RNA>100,000 copies/ml and on-therapy RNA levels below detection limits of commercial assays for ≥ 6 months.
Results: Of 103 patients eligible for analysis, the median age was 46 years and the median duration of viral suppression was 4.8 years. 62% had detectable viraemia (>0.2 copies/ml) by SCA (median 0.2 copies/ml, IQR <0.2-1.8). Younger patients had lower HIV-1 RNA levels than older individuals (r=0.27, P=0.005). Patients with virological suppression on ART for 2 years or less had higher residual viraemia than those with suppression for >2 years (median 2.3 versus 0.2 copies/ml; P=0.016).
Conclusions: Among HIV-1-infected patients with pre-ART HIV-1 RNA>100,000 copies/ml, residual viraemia was detectable in the majority (62%) despite many years of suppressive ART. Higher level viraemia was associated with older age and <2 years of virological suppression on ART. These findings should help in the selection of candidates for clinical trials of interventions designed to eliminate residual viraemia.
Conflict of interest statement
Conflict of interest: JWM is a consultant for Gilead Sciences and RFS Pharma and owns shares in RFS Pharma. JJE is a consultant for Merck, GSK/ViiV, Gilead, Tibotec and Bristol Myers Squibb. He also receives research support from Tobira and GSK/ViiV through the University of North Carolina.
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Source: PubMed