Predictors of residual viraemia in patients on long-term suppressive antiretroviral therapy

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.

Figures

Figure 1

Frequency of screening HIV-1 RNA by single-copy assay

Figure 2. Baseline predictors of HIV-1 RNA by single-copy assay (SCA)

(A) Age (≤ 46, > 46 years) versus HIV-1 RNA by SCA (median age of the study population for this analysis was 46 years). (B) Years (≤ 2 vs. >2) since first HIV-1 RNA below detectable limits by commercial assays versus HIV-1 RNA by SCA. When the SCA measurement was below the detection limit, a value of 1/2 of the detection limit was imputed. The solid horizontal line indicates the median SCA value; the dashed lines indicate 25th and 75th percentile. (The 25th percentile was 0.1 copies/mL for the group with age ≤46 years old and the group with >2 years since first HIV-1 RNA below detectable limits by commercial assays).