Abstract
BackgroundWhether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.MethodsThe associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., “target not detected”), 1–19, 20–399, 400–9999, and ≥10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.ResultsHIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ∼50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.ConclusionHIV RNA ≥10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.
Highlights
Chronic inflammation and increased hemostasis in HIVinfected persons are thought to be a consequence of viral replication or persistence and its associated immune activation
In the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM), we previously reported that markers of inflammation and coagulation remain important predictors of death even at higher CD4+ cell counts [2]
In the SMART trial [5], levels of C-reactive protein (CRP), interleukin (IL)-6 and D-dimer remained elevated in persons with HIV infection even after suppression of HIV RNA with antiretroviral therapy (ART)
Summary
Chronic inflammation and increased hemostasis in HIVinfected persons are thought to be a consequence of viral replication or persistence and its associated immune activation. Elite controllers (HIV-infected persons with undetectable HIV RNA in the absence of ART) had higher levels of the inflammatory marker C-reactive protein (CRP) than HIVuninfected controls [4]. In the SMART trial [5], levels of CRP, interleukin (IL)-6 and D-dimer remained elevated in persons with HIV infection even after suppression of HIV RNA with ART. The SMART trial showed that IL-6 and D-dimer were strongly associated with mortality even in HIV-infected adults who achieved viral suppression [1]. These studies used HIV RNA assays with a lower limit of detection of 75 copies/ml [4] and 400 copies/ml [1]. Whether HIV viremia, at low levels is associated with inflammation, increased coagulation, and allcause mortality is unclear
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