Nineteen instances (39.6%) and forty-three settings (48.9%) were on ART at the time of inclusion (Table 1). Open in a separate window Fig 1 Circulation diagram summarizing the participants selection process. Table 1 Baseline characteristics of instances and controlsa.
SexFemale24 (50.0)43 (47.3)67 (48.2)Male24 (50.0)48 (52.8)72 (51.8)Age (years)39.5 (31.0C50.0)46.0 (37.0C56.0)45.0 (35.0C54.0)Serum concentration of anti-CMV IgG
(IU/ml)18.5 (15.7C23.5)16.2 (13.5C19.8)16.9 (14.8C22.4)Serum concentration of anti-CMV IgG in individuals with values greater than the third tertile (IU/ml)24.2 (19.1C29.8)23.9 (18.9C27.1)24.0 (18.9C29.8)Hypertension19 (39.6)27 (29.7)46 (33.1)Diabetes mellitus1 (2.1)3 (3.3)4 (2.9)Hypercholesterolemia7 (14.6)7 (7.7)14 (10.1)CD4 count (cells/mm3) (9 missing values)136 (75C278)401 (230C533)296 (136C460)ART duration
(3 missing values for controls)No treatment29 (60.4)45 (51.1)74 (54.4)Recent treatment (< 6 months)13 (27.1)7 (8.0)20 (14.7)Long standing treatment
(> 6 months)6 (12.5)36 (40.9)42 (30.9)Tobacco consumptionNever smoked41 (85.4)72 (79.1)113 (81.3)Former smoker3 (6.3)7 (7.7)10 (7.2)Current smoker4 (8.3)12 (13.2)16 (11.5)Alcohol consumption (1 missing value)10 (21.2)16 (17.6)26 (18.8)Previous TIA or stroke8 (16.7)4 (4.4)12 (8.6)Family history of stroke7 (14.6)16 (17.8)23 (16.7)Recent infection (earlier 2 weeks)11 (22.9)14 (15.4)25 (18.0)Waist-hip ratio (1 missing ideals)0.9 (0.86C0.94)0.88 (0.85C0.9)0.88 (0.87C0.89) Open in a separate window a. CD4+ count was 136 and 401 cell/mm3 (IQR: [75C278] and [230C533]) in instances and settings, respectively. High concentration of anti-CMV IgG was associated with ischaemic stroke in the univariable model (OR = 2.56 [1.23C5.34]) but not after adjusting for period of antiretroviral therapy (ART), CD4+ count, and additional cardiovascular risk factors (OR = 0.94 [0.29C3.08]). Low CD4+ count was an independent predictor of stroke. There was a negative correlation between serum concentration of anti-CMV IgG and CD4+ count (rho = -0.30, p < 0.001). Conclusions Large concentration of anti-CMV IgG is not individually associated with ischaemic stroke in HIV-infected Malawians. Larger cohort studies are needed to further investigate the part of humoral response to CMV in the pathophysiology of HIV-associated stroke. Intro Stroke is definitely a global problem but increasing disproportionately in low-to-middle income countries. This is mainly the consequence of lifestyle changes and ageing of the population. HIV illness, which is common in sub-Saharan Africa, contributes to young strokes, and further compounds the stroke burden. Early initiation of antiretroviral therapy (ART) has been shown CHMFL-KIT-033 to reduce the overall risk of stroke . However, a higher stroke risk is still observed in immunosuppressed individuals within the 1st 6 months of ART and among those on longer term treatment. In the second option group, the risk is believed to be driven by atherosclerosis while in the former, it is thought to be related to an immune reconstitution-like process[4, 5]. As our knowledge of the mechanism of HIV-related stroke evolves, the contribution of triggered inflammatory pathways  and chronic infections become more relevant, notably Cytomegalovirus (CMV) illness . In Africa, the prevalence of CMV illness is high, ranging from 81.8% in HIV-negative adults to 94.8% in HIV-positive adults . CMV reactivation reflected by higher CMV-specific T-cell response and improved serum concentration of anti-CMV IgG is definitely associated with surrogate markers of stroke such as carotid intima-media thickness and carotid artery tightness [7, 9]. A few studies have combined non-AIDS events and cardiovascular mortality and shown an association with CMV illness but no study has focused specifically on a stroke cohort[10, 11]. Furthermore, studies conducted thus far, happen to be limited to high-income settings where HIV illness is less common and the disease is less GSS advanced [7, 11, 12]. Medicines to prevent CMV reactivation such as Valganciclovir and newer providers such as Letermovir are available and could eventually be offered to reduce the risk of stroke in HIV-infected individuals if the association between stroke and CMV reactivation is definitely demonstrated CHMFL-KIT-033 throughout the different phases of HIV illness and across the spectrum of cardiovascular disease [13C15]. In this study, we sought to determine the relationship between serum concentration of anti-CMV IgG and ischaemic stroke in a group of HIV-infected individuals from Malawi. Materials and methods Study human population and ethical considerations Our sample was derived from a case-control stroke study in Malawi CHMFL-KIT-033 which recruited 222 stroke instances and 503 settings within the community of Blantyre from 2011 to 2012 . Details of the recruitment process have been reported previously . For each participant, one serum sample was prepared from fresh blood collected within 7 days after stroke onset for instances and on the day of enrolment for settings. After the preparation, the serum was aliquoted and stored at ?70C. The research protocols were authorized by the Liverpool School of Tropical Medicine and the Malawi College of Medicine Study Ethics Committees. A written educated consent was from each participant. This study consisted of a cross-sectional component restricted to the HIV-infected human population in which we examined the relationship between ischaemic stroke and serum concentration of anti-CMV IgG. Measurement of serum concentration of anti-CMV IgG by enzyme-linked immunosorbent assay The concentration of anti-CMV IgG was measured in baseline serum samples using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Genway Biotech Inc., San Diego, USA; catalogue quantity GWB-892399). The kit has a level of sensitivity of 100% and a specificity of 97.6%. The ELISA process was carried out according to the manufacturers instructions and all samples were run in duplicate. The plates were read at 450 nm CHMFL-KIT-033 using an automated reader (Opsys MR, Thermo Fisher Medical Inc., Waltham, USA) and samples were considered as seronegative if they experienced a blank-corrected optical denseness lower or equal to zero. A standard curve was designed for each ELISA plate following the instructions provided with the kit. Intra-assay and inter-assay coefficients of variability (CV) were limited to 10 and 15% respectively. Large serum concentration of anti-CMV IgG was defined as a concentration of anti-CMV IgG.