HIV is associated with premature coronary artery disease (CAD). Recently, a gut microbiome-dependent phosphatidylcholine metabolite, trimethylamine N-oxide (TMAO), has been associated with CAD and mechanistically linked with CAD pathogenesis. However, the relationship between TMAO and both HIV indices and immunosuppression are uncertain.
In this prospective study, we assessed demographic, HIV, and fasting metabolic indices. TMAO was analyzed with mass spectrometry. In 42 subjects, carotid intima media thickness (IMT) was measured by ultrasound.
We assessed 100 consenting HIV+ patients at Cleveland Clinic. The median (IQR) age was 48 (37.4, 52.9). 52 were black; 89 were male. The CD4+ cell counts were median (IQR) 480 (330, 1902) cells/ mm3. HIV-1 RNA were ≤50 copies/mL in 48 subjects and < 200 copies/mL in 74 subjects. Nadir CD4+ cell counts were median (IQR) 196 (64.5, 319.3) cells/ mm3.
TMAO levels were a mean (SD) of 5.06 (7.35) µM. TMAO levels did not correlate with CD4+ cell counts, nadir CD4+ cell count, or log HIV-1 RNA . TMAO levels correlated significantly (r=0.25, p=0.01) with C-reactive protein (hsCRP). Mean (SD) total cholesterol, LDLc, and triglycerides were 187.2 (40.4), 115.0 (36.5), and 147.4 (74.6) mg/dL, respectively. TMAO did not correlate with total cholesterol, LDLc, or triglycerides. In the carotid IMT subgroup, mean (SD) IMT was 0.68 (+/-0.18) mm. 12 of 42 patients (29%) had plaque present; TMAO did not significantly differ between those with and without plaque.
The TMAO levels in the 7 subjects not receiving antiretroviral therapy (ART) tended to be higher than in the 93 subjects receiving ART, but did not reach statistical significance: [mean (SD) =11.0 (22.7) vs. 4.6 (4.6) µM; P=0.49].
In this pilot study of an HIV+ population that is not severely immunosuppressed; TMAO levels did not correlate with CD4+ cell counts or viral load. A trend towards higher levels of the gut-flora dependent CAD marker TMAO in untreated patients would be consistent with reported increased CAD risk with advanced HIV disease. Evaluation of TMAO levels in a larger or more immunosuppressed population, particularly with longitudinal outcome data for incident CAD risks, may add information regarding the microbiome’s effect on CAD risk in HIV+ individuals.
B. Choi, None
J. Fox, None
S. L. Hazen, None