Date Published: August 31, 2017
Publisher: BioMed Central
Author(s): Birry Karim, Ika Praseya Wijaya, Rizky Rahmaniyah, Ibnu Ariyanto, Shelley Waters, Riwanti Estiasari, Patricia Price.
We present a small longitudinal study of how demographic factors and persistent burdens of HIV and cytomegalovirus (CMV) influence cardiovascular health in young adults beginning ART in an inner-city clinic in Jakarta, Indonesia.
ART-naïve HIV patients [n = 67; aged 31 (19 to 48) years] were enrolled in the JakCCANDO Project. Echocardiography and carotid Doppler ultrasonography were performed before ART (V0) and after 3, 6, and 12 months (V3–12). Antibodies reactive with CMV lysate or IE-1 protein were assessed at each timepoint and CMV DNA was identified at V0.
Markers of adverse cardiovascular prognosis [left ventricular mass index, ejection fraction and carotid intimal media thickness (cIMT)] were similar to healthy controls, but increased at V12. Internal diameters of the carotid arteries and systolic blood pressure correlated with HIV disease severity at V0, but cardiac parameters and cIMT did not. E/A ratios (left ventricular diastolic function) were lower in patients with CMV DNA at V0, but this effect waned by V6. Levels of antibody reactive with CMV IE-1 correlated inversely with CD4 T cell counts at V0, and levels at V6–V12 correlated directly with the right cIMT.
Overall the severity of HIV disease and the response to ART have only subtle effects on cardiovascular health in this young Asian population. CMV replication before ART may have a transient effect on cardiac health, whilst antibody reactive with CMV IE-1 may mark a high persistent CMV burden with cumulative effects on the carotid artery.
Several studies have demonstrated accelerated age-related syndromes, such as vasculopathy, in HIV patients assessed in “western” settings. Most have addressed patients over 40 years of age, with consideration to traditional risk factors such as smoking, diet and exercise. In this context, the consensus view ascribes vascular pathology to systemic inflammation in untreated patients, where this declines on antiretroviral therapy (ART) and metabolic factors become dominant [1–3]. Cardiac parameters are less well studied, but Caucasian and African American patients receiving ART had a higher prevalence of diastolic dysfunction and higher left ventricular mass indices (LVMI) than healthy controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection [4, 5]. However, ART changes patterns of cardiac dysfunction from myocarditis [caused by HIV itself or opportunistic infections including cytomegalovirus (CMV)] to syndromes mediated by autoimmunity and antiretroviral drug toxicities . Hence cardiovascular risk in HIV patients on ART is more effectively predicted by the D:A:D algorithm based on Framingham scores and critical anti-retroviral drugs, than by Framingham scores alone . Simulated interventions applied to an Asian population found smoking cessation had the greatest potential impact on 5-year predicted risks of cardiovascular disease, approximating the effect of switching from abacavir to an alternate antiretroviral drug . However abacavir is now used sparingly and the standard regimes cause minimal cardiovascular toxicity .
Study patients were drawn from the 82 individuals enrolled in the JakCCANDO cohort. By V12, six had died, four had withdrawn from ART, two were pregnant and six were lost to follow up. Data are presented for the 46 male and 21 female patients [median (range) age 31 (19 to 48) years], who provided at least one follow-up assessment of vascular health (carotid diameter and cIMT) and cardiac function (E/A ratio, EF, LVMI) (see Table 1). All JakCCANDO patients received triple therapy including lamivudine, zidovudine, nevirapine, stavudine, efavirenz and/or tenofovir. None were prescribed abacavir, so the drugs administered have no confirmed association with vascular pathology . Healthy controls (7 males, 4 females) aged 30 (22 to 38) years were assessed once, and data were compared with published endpoints used in clinical care.Table 1Cardiovascular assessments during the first year on ARTnPre-ART3-months6-months12-monthsHealthy controls6760545511CD4 T-cells/μl63 (2–199)181 (7–601)b202 (6–516)b285 (44–763)b–HIV RNAa5.14 (2.91–6.68)1.89 (0–5.23)b0 (0–5.33)b0 (0–6.32)b–BMI (kg/m2)19.6 (13.2–36.9)20.5 (14.7–39.8)21.7 (16.0–40.1)b23.0 (13.4–40.2)b18.5–25dBP (Systolic)110 (100–150)110 (100–130)110 (110–160)120(100–146)b90–120dBP (Diastolic)80(70–100)80 (60–90)80 (60–100)80(60–90)60–90dEF (%)68 (51–84)c69 (50–83)70 (61–80)70 (50–79)b71 (53–77)E/A Ratio1.3 (0.6–4.7)c1.3 (0.8–1.9)1.3 (0.8–1.9)1.3 (1.1–1.8)1.4 (1.0–1.9)LVMI94 (30–177)99 (52–187)100 (57–217)c102 (47–222)c83 (48–125)cIMT (right, mm)0.58 (0.39–0.64)0.58(0.38–0.77)0.57(0.45–0.90)0.70(0.46–1.0)b0.58 (0.39–0.83)cIMT (left, mm)0.57 (0.32–0.89)0.57(0.39–0.77)0.51(0.32–0.89)0.65(0.45–0.96)b0.58 (0.45–0.70)Diameter (right)e6.4 (4.0–7.9)6.2 (4.3–9)5.9 (4.7–8.3)6.2 (5.1–8.8)(5–7.5)dDiameter (left)e6.1 (3.5–8.1)6.2 (4.1–7.5)6.0 (4.5–8.0)5.8 (4.1–8.0)(5–7.5)dAll data are presented as median (range)BMI, body mass index; BP, blood pressure in mmHg; EF, ejection fraction; E/A ratio, early/late ventricular filling; cIMT, carotid artery intimal thickness; LVMI, Left Ventricular Mass Index. See “Materials and Methods” for detailsaLog10 copies/mlbSignificantly different from V0, Wilcoxon test, p < 0.05cSignificantly different from healthy controls, Mann Whitney test, p < 0.05dNormal range used for clinical care in JakartaeDiameter of the carotid artery (mm) Our study of cardiovascular parameters in a young adult population entering treatment in Jakarta shows subtle changes over the first year on ART. Whilst the small size of our cohort precludes multivariable analyses and corrections for multiple comparisons, it is novel and interesting as a preliminary descriptive study. Low CD4 T-cell counts, high HIV RNA levels and/or the presence of pulmonary tuberculosis at V0 associated with low BMI, smaller diameter of the carotid artery and/or higher systolic blood pressure, but not consistently with markers of cardiovascular health assessed at any time. EF, LVMI and cIMT rose slightly after 12 months on ART, but other parameters were stable. Accordingly at V3, LVMI values correlated directly with CD4 T-cell counts. The rise in EF suggests improved cardiac function, but the higher cIMT and LVMI values suggest a deterioration consistent with poor cardiac outcomes. The latter contrast with a study of Nigerian HIV patients where cardiac disease associated with lower CD4 T-cell counts . However it was a cross-sectional study merging treated and untreated patients, so changes on ART were not captured. Measures of CMV antibodies and DNA display distinct associations with cardiovascular parameters. We propose antibodies reactive with CMV IE-1 as a marker of vascular pathology as levels are relatively stable and correlate with changes to the right carotid artery. Although CMV IE-1 antibodies associate with starting ART with a low CD4 T-cell count, the count itself did not predict changes to either artery. Source: http://doi.org/10.1186/s12981-017-0180-9