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

Abstract

Background: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF. Methods: A long-term first line regimen ART cohort from 2002–2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. Results: A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HRHLLV=5.93, and HRHLB=2.84, p<0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR=3.49, p=0.002), nadir baseline CD4+T cell counts below 200 cells/mm3 (aOR=1.78, p=0.011), Manchu (aOR=2.03, p=0.003), ART over 60 months (aOR=1.81, p=0.004), AZT+3TC+NVP (aOR=2.26, p<0.001) or DDI-based regimen (aOR=9.96, p=0.002), and subtype B’ infection (aOR=8.22, p=0.001). Conclusions: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B’ infection might also predict the occurrence of high-risk LLV.

Association of low‐level viremia with mortality among people living with HIV on antiretroviral therapy in Dehong, Southwest China: A retrospective cohort study

“…For example, a nationwide observational cohort in Sweden found that 9% of the patients had LLV at the end of follow‐up [11], and a study conducted in South Africa reported an LLV proportion of 23% [3]. However, a study from China reported an LLV proportion of 38.7% [22]. Unlike other studies that took proportions of LLV into consideration, we instead focused more on the association between time‐varying LLV and mortality without concretely calculating LLV proportions.…”

Predictors of low‐level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort

“…The definition of LLV and VF has been inconsistent in studies to date [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The main caveat is that most studies included samples with up to 999 HIV-RNA copies/mL, which are actually confirmed cases of VF and introduce uncertainty into the analyses.…”

“…The lack of uniformity with regard to definitions of LLV, blips, optimal virological suppression (VS) and VF makes comparisons of results among different studies inconsistent [9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Characteristics and viral suppression among people living with HIV from the National Free Antiretroviral Therapy Programme, 2019

“…In developed countries, virological suppression is defined as VL < 50 copies/mL [10]. However, approximately 10-30% of patients cannot completely control virus replication [18]. LLV is defined as a plasma VL between 51 and 999 copies/mL, and it is associated with microbial translocation and inflammation.…”

“…PLWH with LLV should be carefully monitored or switched to other regimens. Clinical response to LLV is greatly delayed, which prolongs the duration of LLV and potential for HIV transmission [18]. The diagnostic standard of LLV and regimen-switching decisions urgently need to be reconsidered.…”