title: 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: BACKGROUND
  The 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).
  
  
  METHODS
  ART-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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  Blips 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.
authors.affiliation: Infectious Disease Service, San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Farmer
authors.affiliation: Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD USA ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD USA ; Walter Reed National Military Medical Center, Bethesda, MD USA ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesan
authors.affiliation: Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD USA ; Division of Infectious Diseases, Naval Medical Center of San Diego, San Diego, CA USA ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Deiss
authors.affiliation: Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD USA ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Agan
authors.affiliation: Infectious Disease Service, San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX USA ; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD USA ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: O'Bryan
authors.affiliation: Infectious Disease Service, San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX USA ; United States Army Institute of Surgical Research, Fort Sam Houston, TX USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Akers
authors.affiliation: Infectious Disease Service, San Antonio Military Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX USA ; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD USA.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Okulicz
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use*; D048588:Benzoxazines / Q000097:blood / Q000627:therapeutic use*; D016022:Case-Control Studies; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D057566:Self Report; D019562:Viral Load / Q000187:drug effects* / Q000706:statistics & numerical data; D016903:Drug Monitoring
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz
keywords: Blips; Human immunodeficiency virus; Self-reported adherence