Association of Plasma sVCAM-1 and sCD14 with Mortality in HIV-1 Infected West African Adults with High CD4 Counts

Abstract

Background: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. Here we report the association between eleven biomarkers and medium-term mortality in HIV-infected adults who participated in a trial of early antiretroviral therapy (ART) in West Africa (Temprano ANRS 12136). Methods: In Temprano, ART-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a post-trial phase (PTP). The PTP endpoint was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers (IL-1ra, IL-6, sVCAM-1, sCD14, D-dimer, Fibrinogen, IP-10, sCD163, albumin, hsCRP, 16S rDNA) and all-cause death in the Temprano participants randomized to defer ART. Findings: 477 patients (median age 35, 78% women) were randomly assigned to defer starting ART until the WHO criteria were met. At baseline, the median CD4 count was 379 cells/mm3, the median plasma HIV-1 RNA level 4·6 log10 copies/mL and the median PBMC HIV-1 DNA level 3·0 log10 copies per million PBMC. The participants were followed for 2646 person-years (median 5·8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, PBMC HIV-1 DNA and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥ 1458 vs. < 1458: adjusted hazard ratio [aHR] 2·57, 95% CI 1·13-5·82) and sCD14 (≥ 2187 vs. < 2187: aHR 2·79, IQR 1·29-6·02) levels. Interpretation: In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality. Trial Registration: Registered at Clinical Trials.gov (NCT00495651). Funding Statement: French National Agency for AIDS and viral hepatitis research (ANRS, Paris, France; Grants ANRS 12136, ANRS 12224, ANRS 12253). Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: The Temprano protocol, which included the post-trial phase, was approved by the Cote d'Ivoire National Ethics Committee for Health Research. All patients gave written informed consent.