Pre-cART Inflammatory Biomarker Levels May Predict Long-Term HIV Progression

It is unclear whether markers of microbial translocation and systemic inflammation prior to treatment predict morbidity and mortality during combined antiretroviral therapy.

People living with HIV who have high levels of the inflammatory marker high sensitivity C reactive protein (hs-CRP) before starting combination antiretroviral therapy (cART) may be more likely to experience long-term disease progression, according to the results of a study published in BMC Infectious Diseases. The investigators did not find a correlation between pre-cART microbial translocation and later disease progression.

Although research on suppressive cART in people living with HIV in North America has suggested that biomarkers of systemic inflammation and immune activation may be predictive of mortality, whether markers of microbial translocation and systemic inflammation prior to cART are predictive of morbidity and mortality during treatment is still debated.

A team of investigators from Italy and the United Kingdom explored the possible link between circulating biomarkers of microbial translocation (lipopolysaccharide [LPS], soluble CD14 [sCD14], and endotoxin core antibodies [EndoCAb]) and systemic inflammation (hs-CRP), all measured prior to the initiation of cART, and the risk of long-term disease progression during cART in people living with HIV. Clinical progression was defined as the occurrence of a new AIDS-defining condition, a severe non-AIDS event, or death.

A total of 486 patients (median age, 37 years; 71.4% men) were included in the investigation and contributed 1605 biomarker measures: 278 with LPS, 477 with sCD14, 475 with EndoCAb, and 375 with hs-CRP. The median CD4 T-cell count was 256 cells/mm3, and the median HIV viral load was 4.8 Log cp/mL.

The median time from HIV diagnosis to initiation of cART was 44 months. The median clinical follow-up time, defined as the time between cART initiation and the clinical event or last CD4 count (or available visit), was 79.0 months. There were 125 reported clinical events: 39 patients with AIDS, 66 patients with severe non-AIDS events, and 20 deaths.

Upon measuring the effects of microbial translocation and inflammation via Kaplan-Meier estimation models, the researchers found no major differences in plasma LPS, sCD14, EndoCAb, or hs-CRP in terms of estimating the cumulative probability of disease progression.

After controlling for confounding factors, hs-CRP was the biomarker most strongly linked with clinical progression compared with the other biomarkers (relative hazard, 1.71; P =.081); the higher the hs-CRP level, the greater the risk for clinical progression (P =.056 for a median-based model; P =.002 for a 33% percentile-based model).

“As a consequence, more frequent clinical monitoring and disease-specific screening after cART initiation should be considered for [people living with HIV] showing high levels of hs-CRP while still untreated,” the researchers noted.

“Further research efforts are needed to improve our current understanding of the pathways that connect HIV virus, immune activation/inflammation and the cascade of events leading to the [severe non-AIDS events] before firmly indicating hs-CRP as the main candidate to guide our clinical decisions,” they added.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of authors’ disclosures.


Merlini E, Cozzi-Iepri A, Castagna A, et al. Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV. BMC Infect Dis. 2021;21(1):557. doi:10.1186/s12879-021-06260-y