Diabetes mellitus and associated risk factors among HIV infected patients on HAART.

BACKGROUND: Understanding the impact of disease associations is becoming a priority in Kenya and other countries bearing the load of infectious diseases. With the increased incidences of non-communicable diseases and the endemicity of infectious diseases in Sub-Saharan Africa, their co-existence poses significant challenges to patients, health workers and an overwhelmed health sector. Classical risk factors for diabetes such as physical inactivity and unhealthy diet may not solely explain the current trends, suggesting the role of novel risk factors including infections/inflammation. HIV and its treatment have been identified as potential contributors especially to patients with family history of confirmed diabetes cases. Co-infections frequently observed during HIV infection also significantly influence both the epidemiological and pathophysiological of the link between HIV and diabetes. Understanding the correlates of HIV and diabetes is crucial to inform management and prevention strategies of the twin infections. We therefore aimed to determine the prevalence of diabetes mellitus and risk factors in a population of HIV infected patients on HAART. This study determined the association of diabetes/impaired glucose regulation in the context of HIV-1. A cross-sectional study was conducted at a comprehensive care clinic in Nairobi (Kenya). Participants were screened for diabetes and impaired glucose regulation using random blood glucose and glycated haemoglobin (HbA1c) This paper describes the prevalence of diabetes mellitus in Human Immunodeficiency Virus positive individuals and the associated risk factors. We have demonstrated that family history is a risk factor for diabetes. While age and BMI are known risk factors, they were not associated with diabetes in this study.

Protocol for a Randomized Control Trial for Tungiasis Treatment in Homa Bay County, Kenya: Dimeticone versus Sodium Carbonate.

Tungiasis, a World Health Organization neglected tropical disease, is caused by the female sand flea. Most clinical trials for tungiasis use expensive or impractical drugs, which are difficult for residents to use. However, in western Kenya, communities successfully treat tungiasis with sodium carbonate. We hypothesise that the topical risk-difference of 5% sodium carbonate is no more than 10% non-inferior to dimeticone (NYDA®) for tungiasis treatment. This is a protocol for a non-inferiority study, which will be randomised and with an observer-blinded control. The study will have two arms: 5% sodium carbonate and NYDA®, one on each foot, and will take place at state primary schools in Homa Bay County, Kenya. Fleas identified among school children aged 8-14 years with sand-flea lesions will be enrolled in the study. For each participant, the viability of the embedded fleas, clinical signs including inflammation, and symptoms will be monitored for seven days after treatment. The proportion of dead fleas will be compared in the primary analysis. All adverse events will be monitored throughout the study period. We expect to identify the most effective treatment between sodium carbonate and NYDA® for tungiasis, which can be adopted in the community.

Prevalence of human immunodeficiency virus-1 drug-resistant mutations among adults on first- and second-line antiretroviral therapy in a resource-limited health facility in Busia County, Kenya.

INTRODUCTION: in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression. However, drug-resistance threaten the gains of the HIV infection control program. To determine the prevalence of HIV-1 drug-resistant mutations among adults on ARV therapy attending Khunyangu sub-county hospital in Busia County, Kenya, 50 blood samples were analyzed. METHODS: the samples were collected from November 2019 to January 2020 and tested for HIV-1 viral load. HIV-1 drug-resistance was analyzed through the sequencing of the HIV-1 pol gene. Generated sequences were aligned using RECall (beta v3.05) software. HIV-1 drug-resistance was determined using the Stanford University HIV database. RESULTS: females were 34 and males 16. The general prevalence of HIV-1 drug-resistance was 68%. Out of 34 participants on first-line drugs, 59.9% had mutations against these drugs and 5.9% against the second-line drugs. Out of 16 participants on second-line drugs, 43.8% had mutations against these drugs and 50% against the first-line drugs. The prevalence of mutations encoding resistance to Nucleotide reverse transcriptase inhibitors (NRTIs) were 23(46%); Non-nucleotide Reverse transcriptase inhibitors (NNRTIs), 29(58%) and protease inhibitors (PIs), 7(14%). Dual and multi-class HIV-1 drug-resistance prevalence was as follows: NRTIs + NNRTIs 16(32%); NRTIs + NNRTs + PIs 4(8%); NRTIs + PIs 1(2%). A total of 126 mutations were identified. Predominant NNRTIs mutations were K103N (15), Y181C (9), G190A (7), and H221Y (6) NRTIs, M184V (17), Y115F (5) and PIs, I54V (4). CONCLUSION: the study demonstrates a high prevalence of HIV-1 drug-resistance which calls for intervention for the strengthening of health programs.

Mycobacterium tuberculosis-specific CD8+ T cell recall in convalescing TB subjects with HIV co-infection.

Memory T cell populations recover following phase I chemotherapy for tuberculosis (TB) and augment the effectiveness of antibiotics during the continuation phase of treatment. For those with human immunodeficiency virus (HIV), the CD8(+)T cells may have an especially important role in host defense to Mycobacterium tuberculosis (M.tb) as CD4(+)T cell function and/or numbers decline. Here we performed a preliminary study to investigate the impact of HIV infection status on CD8(+)T cell effector function during the convalescent TB period. Peripheral blood samples from convalescent HIV(+) and HIV(-) TB subjects were used to determine CD4(+)T cell count and monitor antigen-specific CD8(+) T cell activation of effector function (lymphoproliferation, IFN-γ, granulysin) in response to M.tb antigen. Our preliminary results suggest that HIV co-infection is associated with moderate suppression of the M.tb-specific memory CD8(+)T cell compartment in many subjects convalescent for TB. Interestingly, highly activated CD8(+)T cells were observed in recall experiments using peripheral blood from several HIV+ subjects that had low (<200 cells/mm(3)) CD4(+)T cell counts. Further investigation may provide important information for development of novel approaches to target M.tb-specific CD8(+)T cell memory to protect against TB in HIV-endemic regions.

Activation of NK cell granulysin by mycobacteria and IL-15 is differentially affected by HIV.

NK cells play an important role in innate immunity to mycobacteria and are a significant source of the bactericidal effector molecule granulysin. Defects in NK cells have been described in HIV-infected patients, though mechanistic studies have focused on effector molecules relevant to anti-viral, and not anti-bacterial, function. Here we used primary NK cells from healthy human donors and an in vitro system to identify the phenotype of granulysin expressing NK cells, characterize activation stimuli that regulate granulysin, and to study the immediate effects of HIV on innate activation of NK cell granulysin expression. We observe that granulysin expression is co-associated with cytotoxicity receptors (NKp46, NKG2D) known to have important function in the cytotoxic response to M.tb-infected macrophages. Granulysin expression is significantly increased following exposure to IL-15 or Mycobacterium bovis BCG, but in contrast to our previous findings with CD8(+)T cells, expression is weakly activated by IL-21. Infection of PBMC with HIV-1 suppresses NK cell induction of granulysin by IL-15, but does not impair activation by BCG. These effects of HIV-1 are associated with reduced STAT5 phosphorylation in the IL-15 activated signaling cascade. These observations suggest that HIV may impair the anti-bacterial function of NK cells and have implications for clinical use of IL-15 to augment innate cell mediated immunity in HIV+ patients.