Factors associated with HIV viral load “blips” and the relationship between self-reported adherence and efavirenz blood levels on blip occurrence: a case–control study

Abstract

BackgroundThe uncertain etiology of HIV viral load (VL) blips may lead to increased use of clinical resources. We evaluated the association of self-reported adherence (SRA) and antiretroviral (ART) drug levels on blip occurrence in US Military HIV Natural History Study (NHS) participants who initiated the single-tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).MethodsART-naïve NHS participants started on EFV/FTC/TDF between 2006 and 2013 who achieved VL suppression (<50 copies/mL) within 12 months and had available SRA and stored plasma samples were included. Participants with viral blips were compared with those who maintained VL suppression without blips. Untimed EFV plasma levels were evaluated on consecutive blip and non-blip dates by high performance liquid chromatography, with a level ≥1 mcg/mL considered therapeutic. SRA was categorized as ≥85 or <85 %. Descriptive statistics were performed for baseline characteristics and univariate and multivariate Cox proportional hazard models were used to assess the relationship between covariates and blip occurrence.ResultsA total of 772 individuals met inclusion criteria, including 99 (13 %) blip and 673 (87 %) control participants. African-American was the predominant ethnicity and the mean age was 29 years for both groups. SRA ≥ 85 % was associated with therapeutic EFV levels at both blip and non-blip time points (P = 0.0026); however no association was observed between blips and SRA or EFV levels among cases. On univariate analysis of cases versus controls, blips were associated with higher mean pre-treatment VL (HR 1.45, 95 % CI 1.11–1.89) and pre-treatment CD4 count <350 cells/µL (68.1 vs 49.7 %). Multivariate analysis also showed that blips were associated with a higher mean VL (HR 1.42, 95 % CI 1.08–1.88; P = 0.0123) and lower CD4 count at ART initiation, with CD4 ≥500 cells/µL having a protective effect (HR 0.45, 95 % CI 0.22–0.95; P = 0.0365). No association was observed for demographic characteristics or SRA.ConclusionBlips are commonly encountered in the clinical management of HIV-infected patients. Although blip occurrence was not associated with SRA or EFV blood levels in our study, blips were associated with HIV-related factors of pre-ART high VL and low CD4 count. Additional studies are needed to determine the etiology of blips in HIV-infected patients.

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

“…In contrast to previous studies, we focused only on the factors of high-risk LLV subgroup leading to VF, to identify conditions that need prompt treatment during ART. Although we used new definitions of LLV and VF, we found some similar risk factors as several resource-rich cohort studies, including the high zenith VL and low nadir CD4 + T cell counts [3,22,23]. In addition, we found that long-term ART, AZT + 3TC + NVP or DDI + NRTI+NNRTI regimens, Manchu and subtype B′ infection were all risk factors in this study.…”

“…Although most studies suggest that LLV contributes to VF, the potential risk factors of LLV have not been sufficiently investigated. Several HIV cohort studies from developed countries where subtype B was predominant found that the high zenith baseline VL and low nadir baseline CD4 + T cell counts were associated with the risk of LLV [3,[22][23][24][25]. However, the evidence from non-subtype B infected cases and resource-limited regions are still lacking.…”

Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe

“…This study found a significantly higher incidence of viral blips among children compared to adults. The reported incidence of blips varies in different populations (Farmer et al, 2016;Grennan et al, 2012;Havlir et al, 2001;Kanapathipillai et al, 2014;Sorstedt et al, 2016), largely due to different definitions and variability of the assays for VL. We used a common definition of viral blip, as a single VL measurement !50 copies/ml preceded and followed by VL <50 copies/ml (Fung et al, 2012;Ryscavage et al, 2014).…”

“…A proportion of individuals on ART experience low-level viraemia (LLV) and/or transient viraemia; for example, viral blips have been reported in up to 40% of HIV-positive individuals on ART (Grennan et al, 2012;Havlir et al, 2001;Sorstedt et al, 2016). Viral blips have been shown to be associated with higher HIV pretreatment VL and lower CD4 count at the time of ART initiation (Farmer et al, 2016;Havlir et al, 2001;Sorstedt et al, 2016). There is some evidence that they may impair CD4 cell recovery and maintain ongoing low-grade immune activation (Taiwo et al, 2013;Zoufaly et al, 2014).…”

Viral blips during suppressive antiretroviral treatment are associated with high baseline HIV-1 RNA levels

“…Other explanations could be stochastic variations [ 8 ], conditions that temporarily could lead to increased HIV replication such as infections [ 9 ] or vaccinations [ 10 – 12 ], and low drug concentrations in blood because of poor adherence or poor absorption of antiretroviral drugs. Prior studies have reported blip incidence between 13 and 40 % [ 13 – 16 ]. The large differences are due to different blip definitions and viral load assays.…”