Persistent Low-level Viremia While on Antiretroviral Therapy Is an Independent Risk Factor for Virologic Failure

Abstract

Background Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. Methods NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50–199 copies/mL on <25% of measurements), pLLV (VL of 50–199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200–1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. Results Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42–4.93]), and hLV (2.29 [1.78–2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06–1.68]) and antiretroviral use prior to ART (1.79 [1.34–2.38]). Older age at ART initiation (0.71 [0.61–0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51–0.90]) or integrase strand transfer inhibitor use (0.26 [0.13–0.53]) were protective. Conclusion Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.

Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

“…In this study, we observed LLV from 38.7% of participants, and this was much higher than the LLV occurrence (15-20%) in resource-rich settings with similar LLV definition criteria (50-1000 copies/ml) [18,37]. Multiple potential factors could explain these differences, including different ART regimens and frequency of testing [6]. However, because of the strict definition of VF used in this study, the occurrence of VF was substantially lower than previous reported data on both resource-rich regions [38,39] and resource-limited regions [2,7].…”

“…Moreover, most previous studies have only evaluated the impact of different level LLV on VF, without considering the duration of LLV. A few studies found no significant association of low or medium levels LLV with varied duration [5,6,38]. However, the definition of VF in these studies was two consecutive viral loads of at least 500 copies/ml, which is rarely used in practice and differed from that used in this study.…”

“…The plasma of such patients shows low level of viral replication, which is designated as low level viremia (LLV) [4]. Among these cases, the occasionally detected viremia is designated as viral blip (Blip) [5], whereas the continuously detected viremia is designated as persistent low level viremia (pLLV) [6]. The standards of LLV vary greatly with different guidelines.…”

“…However, multiple recent cohort studies worldwide demonstrated that the level of LLV is a determinant of prognosis; high level of LLV (> 200 copies/ml) occurring only once might increase the risk of virologic failure (VF) [7,14,18]. Some studies from developed countries found that persistent LLV or frequently occurring LLV of 50-200 copies/ml also increased the risk of VF [6,19,20]. However, a recent multicenter study from South Africa found that LLV below 200 copies/ml, whether continuous or not, contributed to increased VF risk [2].…”

Virological Outcome After Choice of Antiretroviral Regimen Guided by Proviral HIV-1 DNA Genotyping in a Real-Life Cohort of HIV-Infected Patients

“…39 Similarly a persistent low-level viremia, defined as a VL of 50-199 copies/mL on at least 25% of measurements was associated with virological failure. 40 But clear cutoffs are lacking to allow identification of patients at high risk of virological failure. In our cohort, numerous patients experienced virological control soon after DNA GRT performance in the absence of any ART change.…”