HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

Prevalence and predictors of tuberculosis infection among people living with HIV in a high tuberculosis burden context.

BACKGROUND: Tuberculosis (TB) disease is the leading cause of mortality among people living with HIV (PLHIV). Interferon-gamma release assays (IGRAs) are approved for TB infection ascertainment. However, current IGRA data on the prevalence of TB infection in the context of near-universal access to antiretroviral therapy (ART) and TB preventive therapy (TPT) are lacking. We estimated the prevalence and determinants of TB infection among PLHIV within a high TB and HIV burden context. METHODS: This cross-sectional study included data from adult PLHIV age ≥18 years in whom QuantiFERON-TB Gold Plus (QFT-Plus) assay, an IGRA, was performed. TB infection was defined as a positive or indeterminate QFT-Plus test. Participants with TB and those who had previously used TPT were excluded. Regression analysis was performed to identify independent predictors of TB infection. RESULTS: Of 121 PLHIV with QFT-Plus test results, females were 74.4% (90/121), and the mean age was 38.4 (SD 10.8) years. Overall, 47.9% (58/121) were classified as TB infection (QFT-Plus test positive and indeterminate results were 39.7% (48/121) and 8.3% (10/121), respectively). Being obese/overweight (body mass index ≥25 kg/m2; p=0.013, adjusted OR (aOR) 2.90, 95% CI 1.25 to 6.74) and ART usage for >3 years (p=0.013, aOR 3.99, 95% CI 1.55 to 10.28) were independently associated with TB infection. CONCLUSION: There was a high TB infection prevalence among PLHIV. A longer period of ART and obesity were independently associated with TB infection. The relationship between obesity/overweight and TB infection may be related to ART use and immune reconstitution and requires further investigation. Given the known benefit of test-directed TPT among PLHIV never exposed to TPT, its clinical and cost implications for low and middle-income countries should be explored further.

Prognostic value of biochemical parameters among severe COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

Diagnostic accuracy of the syndromic management of four STIs among individuals seeking treatment at a health centre in Nairobi, Kenya: a cross-sectional study.

INTRODUCTION: the syndromic approach to the management of sexually transmitted diseases (STIs) is recommended in areas without adequate laboratory support. We assessed the diagnostic accuracy of this approach in diagnosing Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG) among 18 to 49 year-old individuals seeking treatment for STIs in a health centre in Nairobi, Kenya. METHODS: participants were recruited between April and June 2019. After providing written informed consent, an interviewer-administered questionnaire was completed. Endocervical swabs from women and urethral swabs from men were collected for STI testing using polymerase chain reaction (PCR). Diagnostic accuracy of reported symptoms was calculated using PCR as the gold standard. RESULTS: a total of 297 individuals (148 men and 149 women) were recruited. Majority of the participants had at least one reported symptom (130/148; 87.8% men and 145/148; 97.3% women). The most commonly diagnosed STI was NG (85/297; 28.6% 95%CI 23.5%-34.1%). Vaginal discharge syndrome had moderate (44.4%) to high (92.9%) sensitivity, low specificity, low positive predictive value (PPV) (2.4 % to 31.5%) and high negative predictive value (NPV) (68.2% to 95.2%). The lower abdominal pain syndrome had moderate to high sensitivity (40% to 71.4%), low specificity (30.9% to 35.6%), low PPV (9.9% to 15.8%) and high NPV (79.2% to 93.8%). The urethral discharge syndrome had high sensitivity (71.4% to 84.8%); moderate specificity (37.6% to 51.7%); low to moderate PPV (5.4% to 53.8%) and high NPV (83.6% to 96.4%). The kappa scores for the three syndromes were generally poor. CONCLUSION: these findings support the need for the review of the syndromic management of STIs.

The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines.

BACKGROUND: Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis. METHODS: Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis. RESULTS: It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4-10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3-6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively. CONCLUSION: This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness.

MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play key regulatory roles in cancer acting as both oncogenes and tumor suppressors. Due to their potential roles in improving cancer prognostic, predictive, diagnostic and therapeutic approaches, they have become an area of intense research focus in recent years. Several studies have demonstrated an altered expression of several miRNAs under hypoxic condition and even shown that the hypoxic microenvironment drives the selection of a more aggressive cancer cell population through cellular adaptations referred as the cancer stem-like cell. These minor fractions of cells are characterized by their self-renewal abilities and their ability to maintain the tumor mass, suggesting their crucial roles in cancer development. This review aims to highlight the interconnected role between miRNAs, hypoxia and the stem-like state in contributing to the cancer aggressiveness as opposed to their independent contributions, and it is based in four aggressive tumors, namely glioblastoma, cervical, prostate, and breast cancers.

Cancer in Kenya: types and infection-attributable. Data from the adult population of two National referral hospitals (2008-2012).

Background: Cancer in Africa is an emerging health problem. In Kenya it ranks third as a cause of death after infectious and cardiovascular diseases. Approximately 15% of the global cancer burden is attributable to infectious agents, with higher percentages in developing countries. Therefore, this study aimed to provide comprehensive hospital based data to inform policies Method: A retrospective survey was conducted at Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH) from 2008 to 2012.  Data was obtained from the patients files using a pre-designed data collection form. The study was approved by the KNH/University of Nairobi and MTRH Ethics and Research Committees. Results: In KNH, the five most common cancers in females (n=300) were cervical 62 (20.7%), breast 59 (19.7%), ovarian 22 (7.3%), chronic leukemia 16 (5.3%), endometrial and gastric both with 15 (5%). In males (n=200) they were prostate 23 (11.5%), laryngeal 19 (9.5%), colorectal 17 (8.5%), esophageal 14 (7.0%) and nasopharyngeal carcinoma 12 (6%). The top infection-attributable cancers were: cervical 62 (12.4%), colorectal 31 (6.2%), gastric 26 (5.2%), prostate 23 (4.6%) and nasopharyngeal carcinoma 17 (3.4%). In contrast, in MTRH the five most common cancers in females (n=282) were breast cancer 74 (26.2%), cervical 41 (14.5%), Kaposi's sarcoma 38 (13.5%), non-Hodgkin's lymphoma 15(5.3%) and ovarian 14 (5%) while in males (n=218) they were Kaposi's sarcoma 55 (25.2%), non-Hodgkin's lymphoma 22 (10.1%),  chronic leukemia 17 (7.8%), colorectal and esophageal cancers both with 16 (7.3%). The top infection-attributable cancers were: Kaposi's sarcoma 93 (18.6%), cervical 41 (8.2%), non-Hodgkin's lymphoma 37 (7.4%), colorectal 27 (5.4%) and liver cancer 16 (3.2%). Conclusion: This study presents a picture of the burden of cancer and infection-attributable cancer from two referral hospitals in Kenya. Reducing the burden of infection-attributable cancers can translate to a reduction of the overall cancer burden.