HIV-negative Control Group Research Articles

Electrocardiographic abnormalities and associated factors among HIV-infected adults on antiretroviral therapy.

Individuals living with HIV are at increased risk of developing cardiovascular diseases. This heightened vulnerability is influenced by various factors, including the direct impact of HIV infection, the side effects of HIV medications, and a higher presence of traditional cardiovascular risk factors. Detecting and managing cardiovascular diseases early in HIV-infected individuals is crucial for their overall health and well-being. Electrocardiography, a simple and non-invasive test, can provide valuable information in this regard. However, there is currently no published data on the prevalence of electrocardiographic abnormalities and the associated factors among HIV-infected adults in Ethiopia. This study was aimed at assessing the prevalence of ECG abnormalities and associated factors among HIV-infected adults on antiretroviral therapy. A hospital-based comparative cross-sectional study was conducted at Mettu Karl Specialized Hospital (MKSH), southwest Ethiopia, among 96 HIV-infected patients and 96 HIV-negative control groups. A systematic random sampling technique was used to select HIV-infected respondents, and HIV-negative respondents were purposively recruited from caregivers. A face-to-face interview with a semi-structured and pretested questionnaire was conducted to collect the socio-demographic and behavioral characteristics of the study participants. Electrocardiography was done for all study participants using a 12-lead electrocardiograph, interpreted by a cardiologist, and classified according to the Minnesota Code classification system. The data were entered into Epi-Data version 4.6 and exported to SPSS version 25 for analysis. Finally, descriptive statistics, chi-square, independent t-test, bivariable, and multivariable logistic regression analyses were done at a 5% significance level. The study found that 49% of HIV-infected and 19.8% of HIV-negative participants had at least one ECG abnormality. The proportion of coded ST-segment abnormalities, T-wave abnormalities, longer QT interval, and sinus tachycardia was significantly higher in HIV-infected respondents than in HIV-negatives. Being a smoker [AOR = 3.7, 95%CI: 1.03-13.6], being on Protease inhibitors [AOR = 3.6, 95%CI: 1.02-13.1] and having CD4 less than 350 cells/mm3 [AOR = 3.2, 95%CI: 1.22-8.49] were significantly associated with ECG abnormalities among HIV-infected respondents. Compared to HIV-negative participants, HIV-infected patients had a significantly higher prevalence of ECG abnormalities. Screening for ECG abnormalities is needed for the early detection of cardiac abnormalities and the reduction of future complications.

Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV

Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately. To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group. Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023. Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event. Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis. The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure. A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and β-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62). These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Metabolic dysfunction-associated steatotic liver disease in people with HIV is associated with lower BMI and more liver fibrosis compared to the uninfected population

Aim: People with HIV (PWH) are at high risk of metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the presence of hepatic steatosis plus any among overweight, diabetes, hypertension, or dyslipidemia. There are limited data whether MASLD in PWH differs in clinical presentation from MASLD in the uninfected population. Aim: to compare the severity of metabolic and hepatic dysfunction between MASLD patients with and without HIV. Methods: 212 consecutive HIV mono-infected patients with MASLD at McGill University in Montreal were compared to a sex and age matched MASLD HIV negative control group at Policlinico Hospital in Milan. Fibroscan with controlled attenuation parameter (CAP) was used to define MASLD (CAP≥248 dB/m), severe MASLD (CAP>280 dB/m), and significant liver fibrosis (liver stiffness measurement>7.0 kPa). Results: PWH with MASLD presented lower median BMI (28[25-31] vs 29[27-32] Kg/m2, p=0.002) and lower prevalence of obesity (26% vs 44%, p<0.001) compared to MASLD uninfected patients, along with a lower prevalence of hypertension (21% vs 38%, p<0.001). The prevalence of dyslipidemia (41% vs 26%, p<0.001), hypertriglyceridemia (26% vs 9%, p<0.001) and low HDL cholesterol (34% vs 15%, p<0.001) was higher in MASLD patients with vs without HIV. No difference in cardiovascular events and diabetes prevalence was observed between the two groups. Regarding liver disease, PWH with MASLD had lower prevalence of severe MASLD (54% vs 74% p<0.001) but higher prevalence of significant liver fibrosis (15 vs 7%, p=0.03) compared to MASLD uninfected patients. After adjustment, HIV positivity was an independent factor associated with significant liver fibrosis (figure). Conclusions: Despite having lower BMI, PWH with MASLD have a more severe hepatic presentation and atherogenic lipid profile than MASLD uninfected patients. HIV positivity seems to be independently associated with significant liver fibrosis. Screening and follow-up for MASLD and liver fibrosis is recommended in PWH, even if they are lean.

Impact of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Fetal Subcutaneous Fat Tissue in HIV-Pregnant Women in a Middle-Income Country.

HIV infection continues to be a global public health challenge, affecting approximately 1.7 million reproductive-aged women. Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has significantly reduced the risk of vertical transmission of HIV from mother to child. Nevertheless, concerns linger regarding the long-term effects, particularly on body composition, notably subcutaneous fat tissue (SFT). Although HIV-associated lipodystrophy syndrome (LS) has been well documented in adults and older children, its impact on fetuses exposed to PI-HAART remains underexplored. This study aims to evaluate SFT in the fetuses of HIV-pregnant women exposed to PI-HAART, assessing the potential clinical implications. We conducted a comparative study between HIV-pregnant women receiving PI-HAART and an HIV-negative control group. Fetometry measurements were obtained via 3D ultrasound. SFT in the fetal arm and thigh segments was assessed. Data were analyzed using lineal multivariate regression and receiver-operating characteristics (ROC)-curve analysis. Fetuses exposed to PI-HAART exhibited a significant reduction in subcutaneous fat, particularly in the proximal third-middle union of the femur (coefficient: -2.588, p = 0.042). This reduction was correlated with lower newborn serum glucose levels (65.7 vs. 56.1, p = 0.007; coefficient: -1.277, p = 0.045). Our study sheds light on the connection between PI-HAART, fetal subcutaneous fat, and neonatal health. These findings might reveal the long-lasting effects of PI-HAART on newborns and children's well-being. Our results emphasize the need for a more balanced approach to managing pregnant women with HIV in developing countries and open new venues for research on the impact of intrauterine PI-HAART exposure on energy metabolism and fetal programming.

Liver transient elastography values in healthy South African children

BackgroundTransient elastography (TE) is a rapid noninvasive ultrasound-based technology that measures liver stiffness as a surrogate for liver fibrosis and controlled attenuation parameter (CAP) as a measure of liver steatosis. However, normal ranges in children are not well defined in all populations. The aim of this study was to determine transient elastography values in healthy South African children.MethodsFrom April 2019 to December 2021, children were recruited from the HIV negative control group of a cohort study. Only children neither overweight nor obese, without evidence of liver disease, no medical condition or medication associated with hepatic steatosis or fibrosis and normal metabolic profile were included in this cross-sectional analysis. Clinical data, anthropometry and blood samples were collected on the same day as transient elastography with controlled attenuation parameter was performed.Results104 children (median age 12.8 years [IQR 11.4–14.8, range 7.9–17.7 years]; 59 [57%] boys) were included. Liver stiffness was positively correlated with age (Pearson’s r = 0.39, p < 0.001). Median liver stiffness in boys (5.2 kPa [5th to 95th percentiles 3.6 to 6.8 kPa]) was greater than in girls (4.6 kPa [5th to 95th percentiles 3.6 to 6.1 kPa; p = 0.004]), but there was no difference by ethnicity. Median CAP was 179dB/m (5th to 95th percentiles 158 to 233dB/m). There was a positive correlation between CAP and body mass index (BMI) z-score, but no difference by age, sex, ethnicity or pubertal status.ConclusionLiver stiffness values increase with age and are higher in healthy South African boys than girls, whereas CAP values vary with BMI, but not with age or sex.

The integrity of psychophysical visual function in non-immunocompromised PLHIV (NIPLHIV) without retinitis on antiretroviral therapy (ART).

The present study investigated the integrity of contrast sensitivity (CS), colour vision, and pattern evoked vision potentials (VEP) in non-immunocompromised people living with HIV (NIPLHIV) without retinitis. All participants were visually asymptomatic and no history of ocular disorders, with CD4 counts above 350 cells/mm3, low viral loads and on ART. Thirty NIPLHIV and 30 age-matched HIV negative control groups underwent F100 hue colour assessment, Pelli-Robson contrast sensitivity assessment and pattern-reversal VEP. The median F100 total error scores for NIPLHIV and controls was 33 (IQR: 28;41) and 28 (IQR: 26;48.50) respectively, this was statistically different (p= 0.020). The median P100 amplitude for NIPLHIV was 5.75 µV (IQR: 4.4;8.85) and 4.05 µV (IQR: 3.2;5.8) for controls, this was statistically different (p=0.045). The mean LogCS score 1.83±0.14 and the median P100 peak latency was 105.45 msec (IQR: 102.98;108.98) for NIPLHIV. Higher CD4+ counts were significantly associated with having higher F100 total error scores (OR=0.995; p=0.018), lower P100 amplitudes (OR=1.007; p=0.010) and higher P100 latencies (OR=0.994; p=0.011). Contrast sensitivity function, colour vision, and VEP were uncompromised in NIPLHIV. Associations between CD4 counts with F100 total error scores and P100 latency may aid in the surveillance of vision of NIPLHIV.

Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV.

Despite the development of vaccines, which protect healthy people from severe and life-threatening Covid-19, the immunological responses of people with secondary immunodeficiencies to these vaccines remain incompletely understood. Here, we investigated the humoral and cellular immune responses elicited by mRNA-based SARS-CoV-2 vaccines in a cohort of people living with HIV (PLWH) receiving anti-retroviral therapy. While antibody responses in PLWH increased progressively after each vaccination, they were significantly reduced compared to the HIV-negative control group. This was particularly noteworthy for the Delta and Omicron variants. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase, which was comparable in both groups. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4+ T cell numbers do not necessarily interfere with cellular immune responses. Our data demonstrate that despite the lower CD4+ T cell counts SARS-CoV-2 vaccination results in potent cellular immune responses in PLWH. However, the reduced humoral response also provides strong evidence to consider PLWH as vulnerable group and suggests subsequent vaccinations being required to enhance their protection against COVID-19.

Health-Related Quality of Life Among HIV-Infected Children and Its Association With Socio-Demographic, Clinical and Nutritional Variables: A Comparative Approach.

Background: The human immunodeficiency virus (HIV) infection and its treatment impact the child’s life as well as that of their caregivers. As therapeutic advances are made in the field, improved survival has shifted the focus from morbidity and mortality to quality of life. This study aims to compare the health-related quality of life (HRQoL) of children living with HIV in comparison with an HIV-negative control group and determine its relationship with socio-demographic, clinical, and nutritional variables.Method: This was a multi-center cross-sectional comparative study involving 274 participants (137 per group) carried out in tertiary and secondary level healthcare facilities in Nigeria. Socio-demographic, clinical, and nutritional variables were obtained using a researcher-designed data collection sheet. HRQoL was measured using the Paediatrics Quality of Life Inventory (PedsQL 4.0), while caregivers’ burden was assessed using the Zarit-Burden Interview (ZBI). A comparison of the health-related quality of life of the cases and the control group was done using an independent t-test. The predictors of HRQoL among the cases were measured using multivariate stepwise linear regression analysis.Result: The overall health-related quality of life of HIV-infected children and those of the HIV-negative control group were similar. However, there was a significant difference in the school and psychosocial functioning domains between the two groups with HIV-positive children scoring lower in these domains. For HIV-positive children, being from upper social class (p = 0.01, R2 = 0.098), male gender (p = 0.005, R2 = 0.063), higher scores in the caregiver burden scale (p = 0.009, R2 = 0.150) and more disease severity (p < 0.001, R2 = 0.321) were significant predictors of lower health-related quality of life.Conclusion: The findings of this study show that the overall health-related quality of life of HIV-positive children was similar to that of age- and sex-matched HIV-negative control group. This finding gives clinicians some optimism that with adequate treatment, HIV-positive children will have better outcomes not only in mortality but in psychosocial variables such as quality of life. In addition, the finding on the relationship between caregiver burden and HRQoL underscores the need to focus on family-based interventions to improve the burden of caregiving on family members involved in the care of HIV-positive children.

Covid-19 vaccine immunogenicity in people living with HIV-1

IntroductionCOVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals’ response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals. MethodsHIV-positive individuals (n = 121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naïve to SARS CoV-2 was used. The participants’ Anti-RBD IgG responses were measured by ELISA at baseline and 3–4 weeks after receiving the first dose of an mRNA vaccine). ResultsEleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between the HIV negative control group (n = 20) and the combined HIV+ group (n = 106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm3. (p < 0.0001). Increasing age was independently associated with decreased immunogenicity. ConclusionHIV-positive individuals with CD4 counts over 250 cells/mm3 have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm3) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose.

Increased risk of mental illness in people with HIV.

People with HIV who are diagnosed promptly and treated can now anticipate a life expectancy similar to that of people without HIV.1 However, despite this remarkable narrowing of the gap in mortality risk, a stark disparity in mental health, evident in the early days of the epidemic,2 appears to persist. Studies across a range of countries and settings, using various measurement tools, have consistently found a high burden of depressive symptoms among people with HIV,3 with some reporting a two times higher prevalence compared with the general population or HIV-negative control groups.

Age at menopause in women living with HIV: a systematic review.

With improved HIV care, more women living with HIV (WLWH) are aging and entering menopause. Understanding any increased risk conferred by a potentially earlier menopause transition is important for the care of these women. There is conflicting literature regarding the association between HIV and an earlier onset of menopause. We conducted a systematic review to summarize the literature on the association between HIV and age at menopause. A search of Ovid MEDLINE, EMBASE, and Web of Science identified 894 articles. We included cohort studies that assessed age at menopause, primary ovarian insufficiency (POI), or early menopause among WLWH and used the World Health Organization definition of menopause as ≥12 months of amenorrhea. Nine studies were included and eight reported on age at menopause. Across studies, the age at menopause for WLWH fell between 46 and 50 years. Five of seven studies reported that WLWH had an earlier menopausal transition than HIV negative controls/the general population. Six studies reported on the prevalence of POI or early menopause among WLWH, with all studies demonstrating an increased prevalence of both among WLWH. Our systematic review summarizes the literature around HIV and age at menopause. Many studies reported a high prevalence of POI and early menopause among WLWH; a factor that may partially account for the observed lower age at menopause. As only one study included biochemical confirmation of menopause, it remains unclear whether individuals with early menopause or POI were truly menopausal or had prolonged amenorrhea due to other causes. Overall, our findings highlight the need for further investigation with studies that include an HIV negative control group and biochemical confirmation of menopause to better understand whether menopause truly is occurring earlier among WLWH.

Relationships Between Viral Load, Neuroimaging, and NP in Persons Living With HIV.

This study examined whether recommended viral load (VL) classifications by the Department of Health and Human Services map onto changes in brain integrity observed in people living with HIV (PLWH). Three hundred forty-nine PLWH on combination antiretroviral therapy meeting criteria for virologic suppression (VS) (VL ≤ 20 copies/mL; n = 206), "low-level viremia" (20-200 copies/mL; n = 63), or virologic failure (VF) (>200 copies/mL; n = 80) and 195 demographically similar HIV-negative controls were compared for cognition and brain volumes from 10 regions of interest that are sensitive to HIV. Changes in cognition and brain volumes were examined in a subset of PLWH (n = 132) who completed a follow-up evaluation (mean interval = 28 months) and had no change in treatment regimen. Significant differences in cognition and brain volumes were observed between the HIV-negative control and VS groups compared with those in the VF groups, with few differences observed between the 3 PLWH subgroups. Longitudinally, PLWH who continued to have VF exhibited a greater decline in cognition and brain volumes compared with PLWH who remained with VS. Observed longitudinal changes in cognition correlated with brain volume changes. PLWH with continued VF (consecutive VL measurements of >200 copies/mL) represent a cause for clinical concern and may benefit from change in treatment in addition to consideration of other potential etiologies of VF to reduce loss of brain integrity.

Study of cervical cytological changes in HIV patients

Patients with HIV have an increased incidence of abnormal cervical cytological changes. This case-control study (30 cases, 30 controls) was aimed at demonstrating these findings. Both symptomatic and asymptomatic pre-menopausal women of 20-50 years were included in the study. Conventional Pap smears were taken and examined by cytopathologists. HIV cases had more incidence of abnormal cervical cytology (13 cases, 43.33%) than their sero-negative counterparts (5 cases, 16.67%).Out of the 13 cases, 2(6.66%) had LSIL and 1(3.33%) was with ASC-US, specific infections with coccobacilli, T. vaginalis and Candida was found in a total of 5 samples (16.67%) against only 1 t. vaginalis infection (3.33%) in the control group. Reparative changes (squamous metaplasia) was seen in 5 cases (16.67%) of the HIV positive group and in 2 cases (6.66%) in the control group. There was no case of malignancy in the HIV positive group, in contrast to the HIV negative control group which presented a single case of malignancy and another case of HSIL. The study showed that HIV infection was associated with an increased incidence of opportunistic infections along with dysplasias of the cervix. The cases with Dysplasia should be followed up to screen for malignant transformation.

Cardiovascular magnetic resonance imaging reveals asymptomatic cardiomyopathy in newly diagnosed, HIV-infected South African adults

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): University of Stellenbosch Cardiology Research Fund and United States National Institutes of Health/Fogarty International Center Background Cardiovascular disease (CVD) is a leading cause of death and disability in people living with HIV (PLWH). The coronary disease burden in high income countries contrast what is experienced in low- and middle-income countries where cardiomyopathy remains prevalent. Cardiovascular magnetic resonance imaging (CMR) has the unique ability to characterise tissues to obtain "virtual histology". Our data support a high burden of myocardial disease, already present at the time of HIV diagnosis in a young South African cohort. Purpose Early, undiagnosed myocardial pathology in some antiretroviral therapy (ART) naïve persons appear to precede the development of poorly prognostic HIV associated cardiomyopathy. The burden and mechanisms underlying the progression to more advanced disease in treatment naïve PLWH remain largely unknown, as does the modifying effect of ART on these abnormalities. Studying early myocardial disease and its progression with serial CMR evaluation will improve our understanding of disease evolution. Methods 24 newly diagnosed, ART naïve adults without known CVD underwent a contrasted, 1.5T CMR study. Assessments included: Left ventricular (LV) volumes, mass, ejection fraction (EF), native and post-contrast T1 mapping, T2 mapping, extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging. Quantitative measurements were obtained using a semi-automated software. Qualitative LGE findings were reviewed by an EACVI level III accredited cardiologist. Results The median age of the cohort was 33, interquartile range (IQR) 30-43 years. Median CD4 count was 250, IQR 152-520 cells/uL. All patients had non-dilated LV"s according to indexed end diastolic volumes (Mean: 85 ± 15ml/m²). No patient had overt systolic dysfunction (Mean EF: 62 ± 6%). Non-trivial pericardial effusions were present in 71% of cases. Indexed LV mass measured normal (Mean: 65 ± 12g/m²). Mean global native T1 and T2 values were 1043 ± 46 and 49 ± 4ms respectively. Native T1 values were highest in the septum and inferior wall (Mean: 1054 ± 50 and 1047 ± 51ms respectively). Mean global ECV was 28 ± 4%. Non-ischaemic LGE was present in 71% of participants. In those with LGE, midmyocardial enhancement of the inferior septum represented 71% of abnormalities (Figure). Conclusion In this young cohort of newly diagnosed HIV-infected persons, the prevalence of myocardial abnormalities were high. The midmyocardial LGE and abnormal mapping parameters (high for our scanner and high normal for published data) suggest myocardial inflammation and fibrosis already present at HIV-diagnosis. This was most appreciable in the septum and inferior walls, and likely represents a diffuse process that may progress to symptomatic cardiomyopathy over time. Serial evaluation on ART and comparison with a matched HIV-negative control group is planned. This will allow quantitative comparison of tissue characterisation and explore the nature and evolution of these abnormalities. Abstract Figure. Late gadolinium enhancement (Arrows)

Basic fibroblast growth factors as a biomarker of focal segmental glomerulosclerosis in HIV-positive and HIV-negative children

Background. HIV infection can lead to the development of HIV-associated nephropathy (HIVAN) with the majority of patients progressing to end-stage kidney disease. Previous studies have recognised basic fibroblast growth factor (bFGF) as a biomarker for HIVAN, since significant levels of bFGF low-affinity receptors have been found in the kidneys of HIV-infected children. Objective. To assess the association between bFGF and kidney disease in the development of focal segmental glomerulosclerosis (FSGS) in HIV-positive and negative children. Methods. The study group consisted of 31 children; HIVAN ( n =11) and idiopathic FSGS ( n =20). The control group consisted of both HIV-positive ( n =20) and HIV-negative ( n =20) children with no kidney disease. Serum samples from all patients in both the study and control groups were analysed for bFGF. Results . The concentration of bFGF was higher, in comparison with idiopathic FSGS children, in HIVAN children ( p =0.0167). There was also a significant elevation of serum bFGF levels in children with HIVAN when compared with HIV-positive ( p =0.0288) and HIV-negative ( p =0.0043) control groups. Conclusion. This study demonstrated statistically significant differences between bFGF levels in children with HIVAN and a control group, although it failed to distinguish significant differences in bFGF levels between HIVAN and idiopathic FSGS children.

Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1

BackgroundSome multifunctional cellular proteins, as the monocyte chemotactic protein-induced protein 1 (ZC3H12A/MCPIP1) and the cyclin-dependent kinase inhibitor CDKN1A/p21, are able to modulate the cellular susceptibility to the human immunodeficiency virus type 1 (HIV-1). Several studies showed that CDKN1A/p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC) and a recent study supports a coordinate regulation of ZC3H12A/MCPIP1 and CDKN1A/p21 transcripts in a model of renal carcinoma cells. Here, we explored the potential associations between mRNA expression of ZC3H12A/MCPIP1 and CDKN1A/p21 in HIC sustaining undetectable (elite controllers–EC) or low (viremic controllers–VC) viral loads.ResultsWe found a selective upregulation of ZC3H12A/MCPIP1 and CDKN1A/p21 mRNA levels in PBMC from HIC compared with both ART–suppressed and HIV–negative control groups (P≤ 0.02) and higher MCPIP1 and p21 proteins levels in HIC than in HIV-1 negative subjects. There was a moderate positive correlation (r ≥ 0.57; P ≤ 0.014) between expressions of both transcripts in HIC and in HIC combined with control groups. We found positive correlations between the mRNA level of CDKN1A/p21 with activated CD4+ T cells levels in HIC (r ≥ 0.53; P ≤ 0.017) and between the mRNA levels of both CDKN1A/p21 (r = 0.74; P = 0.005) and ZC3H12A/MCPIP1 (r = 0.58; P = 0.040) with plasmatic levels of sCD14 in EC. Reanalysis of published transcriptomic data confirmed the positive association between ZC3H12A/MCPIP1 and CDKN1A/p21 mRNA levels in CD4+ T cells and monocytes from disparate cohorts of HIC and other HIV-positive control groups.ConclusionsThese data show for the first time the simultaneous upregulation of ZC3H12A/MCPIP1 and CDKN1A/p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo and the positive correlation of the expression of these cellular factors in disparate cohorts of HIV-positive individuals. The existence of a common regulatory pathway connecting ZC3H12A/MCPIP1 and CDKN1A/p21 could have a synergistic effect on HIV-1 replication control and pharmacological manipulation of these multifunctional host factors may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.

Middle ear Pathologies in Adults Living with Human Immunodeficiency Virus: A Systematic Review.

Middle ear pathologies have been linked with HIV. The onset and development of these pathologies in individuals with HIV have not been categorized; and clarity has not been gained regarding whether their presentation is any different in this population when compared to HIV negative control group. The aim of this study was to explore and document published evidence reflecting trends in middle ear pathologies in adults living with HIV. A systematic review of literature from January 1982 to December 2018 was conducted using Medline, CINAHL, PubMed, and Psych Info. Studies that reported the occurrence rate of middle ear pathologies in adults with HIV and published in English were included. Twelve articles met the inclusion criteria. Evidence suggests that the reported occurrence rates of middle ear pathologies ranges from 2.5% to 58% in this population. The variability in assessment measures as well as the different cut-off criteria used in studies seem to have an influence in the findings, with pure tone audiometry identifying more middle ear pathologies in the current review than tympanometry with 226 Hz probe tone and clinical examination. Otitis media, conductive hearing loss, and type B tympanogram were common findings reported in this study. No evidence of an association between the use of antiretroviral therapy (ART) and the rates of middle ear pathologies was found. Although there are very few studies that have reported on middle ear pathologies in adults living with HIV, the available studies have sufficiently established a link between HIV and middle ear disease in this population, and have revealed that the rate of occurrence is influenced by a number of factors. Key amongst these is the type of assessment measure used. Careful analysis of middle ear pathologies in this population through well controlled research designs that include different assessment measures. The use of case-control and longitudinal designs to determine differences between groups and to establish the time of onset and development of middle ear pathologies is required.

Significant effect of HIV/HAART on oral microbiota using multivariate analysis

Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.

Unexpected low frequency of respiratory symptoms in an HIV-positive urban sub-Saharan population compared to an HIV-negative control group.

BackgroundChronic respiratory illnesses and respiratory infections are common in HIV-positive populations. It seems reasonable that HIV-positive people experience more respiratory symptoms, such as coughing and breathlessness, than those who are HIV-negative.ObjectivesThis study aims to determine the frequency of respiratory symptoms in an urban African HIV-positive population.MethodA cross-sectional study was conducted in Johannesburg, South Africa, in 2016–2017. Four groups of participants were included: HIV-positive participants (1) not yet on antiretroviral therapy (ART), (2) on first-line ART, (3) on second-line ART and (4) age- and sex-matched HIV-negative controls. Data were collected on socio-demographics, respiratory risk factors and respiratory symptoms. A logistic regression analysis was performed to determine if respiratory symptoms differed between groups and to identify determinants associated with symptoms.ResultsOverall, 547 participants were included, of whom 62% were women, with a median age of 37 years. Of these patients, 63% (347) were HIV-positive, 26% were ART-naïve, 24% were on first-line ART and 50% were on second-line ART. Cough and/or productive cough was reported by 27 (5%), wheezing by 9 (2%) and breathlessness by 118 (22%) of the participants. The frequency of these symptoms did not differ by HIV status after adjustment for age and sex. Breathlessness was associated with age, female sex, obesity, a history of respiratory infection and a history of airway hyper-reactivity.ConclusionThe frequency of respiratory symptoms was low in our study population except for breathlessness. HIV-positive participants, whether or not on ART, did not experience more symptoms than HIV-negative participants.

CT Texture Analysis of Cervical Lymph Nodes on Contrast-Enhanced [18F] FDG-PET/CT Images to Differentiate Nodal Metastases from Reactive Lymphadenopathy in HIV-Positive Patients with Head and Neck Squamous Cell Carcinoma.

Differentiating nodal metastases from reactive adenopathy in HIV-infected patients with [18F] FDG-PET/CT can be challenging because lymph nodes in HIV-positive patients often show increased [18F] FDG uptake. The purpose of this study was to assess CT textural analysis characteristics of HIV-positive and HIV-negative lymph nodes on [18F] FDG-PET/CT to differentiate nodal metastases from disease-specific nodal reactivity. Nine HIV-positive patients with head and neck squamous cell carcinoma (7 men, 2 women; 29-62 years of age; median age, 48 years) with 22 lymph nodes (≥1 cm) who underwent contrast-enhanced CT with [18F] FDG-PET followed by pathologic evaluation of cervical lymph nodes were retrospectively reviewed. Twenty-six HIV-negative patients with head and neck squamous cell carcinoma with 61 lymph nodes were evaluated as a control group. Each lymph node was manually segmented, and an in-house-developed Matlab-based texture analysis program extracted 41 texture features from each segmented volume. A mixed linear regression model was used to compare the pathologically proved malignant lymph nodes with benign nodes in the 2 enrolled groups. Thirteen (59%) lymph nodes in the HIV-positive group and 22 (36%) lymph nodes in the HIV-negative control group were confirmed as positive for metastases. There were 7 histogram features (P = .017-0.032), 3 gray-level co-occurrence features (P = .009-.025), and 9 gray-level run-length features (P < .001-.033) that demonstrated a significant difference in HIV-positive patients with either benign or malignant lymph nodes. CT texture analysis may be useful as a noninvasive method of obtaining additional quantitative information to differentiate nodal metastases from disease-specific nodal reactivity in HIV-positive patients with head and neck squamous cell carcinoma.