Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease

Abstract

Objective: The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals.

Design: A cross-sectional study.

Methods: Combination antiretroviral therapy (cART)-treated adults participating in an international HIV trial with haemoglobin and mean corpuscular volume (MCV) measurements at entry were categorized by presence of anaemia (haemoglobin ≤14 g/dl in men and ≤12 g/dl in women) and, for those with anaemia, by type [microcytic (MCV < 80 fl), normocytic (80-100 fl), macrocytic (>100 fl)]. We analysed the association between inflammation (IL-6 and hsCRP) and coagulation (D-dimer) and haemoglobin, controlling for demographics (age, race and sex), BMI, HIV plasma RNA levels, CD4⁺ T-cell counts (nadir and baseline), Karnofsky score, previous AIDS diagnosis, hepatitis B/C coinfection and use of zidovudine.

Results: Among 1410 participants, 313 (22.2%) had anaemia. Of these, 4.1, 27.2 and 68.7% had microcytic, normocytic and macrocytic anaemia, respectively. When compared with participants with normal haemoglobin values, those with anaemia were more likely to be older, black, male and on zidovudine. They also had lower baseline CD4⁺ T-cell counts and lower Karnofsky scores. Adjusted relative odds of anaemia per two-fold higher biomarker levels were 1.22 (P = 0.007) for IL-6, 0.99 for hsCRP (P = 0.86) and 1.35 (P < 0.001) for D-dimer. Similar associations were seen in those with normal and high MCV values.

Conclusion: Persistent inflammation and hypercoagulation appear to be associated with anaemia. Routine measurements of haemoglobin might provide insights into the inflammatory state of treated HIV infection.

Figure 1

Associations between anemia and biomarkers across MCV levels^{a a}The number of anemic patients with MCV< 80 (N=11) was too low to calculate ORs. Adjusted ORs for patients with normocytic anemia (MCV 80–100) were 1.27 (P= 0.09) for D-dimer and 1.18 (P= 0.17) for IL-6. ^bAdjusted for demographics (age, race, gender), BMI, HIV RNA levels, CD4+ cell counts (nadir and baseline), Karnofsky score, previous AIDS diagnosis, hepatitis B and C co-infection and use of zidovudine. Log₂-transformed levels of IL-6, hsCRP and D-dimer were adjusted for simultaneously.