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The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection.
Alvarez, N, Aguilar-Jimenez, W, Rugeles, MT
Frontiers in immunology. 2019;:2291
Abstract
HIV infection remains a global and public health issue with the incidence increasing in some countries. Despite the fact that combination antiretroviral therapy (cART) has decreased mortality and increased the life expectancy of HIV-infected individuals, non-AIDS conditions, mainly those associated with a persistent inflammatory state, have emerged as important causes of morbidity, and mortality despite effective antiviral therapy. One of the most common comorbidities in HIV-1 patients is Vitamin D (VitD) insufficiency, as VitD is a hormone that, in addition to its physiological role in mineral metabolism, has pleiotropic effects on immune regulation. Several reports have shown that VitD levels decrease during HIV disease progression and correlate with decreased survival rates, highlighting the importance of VitD supplementation during infection. An extensive review of 29 clinical studies of VitD supplementation in HIV-infected patients showed that regardless of cART, when VitD levels were increased to normal ranges, there was a decrease in inflammation, markers associated with bone turnover, and the risk of secondary hyperparathyroidism while the anti-bacterial response was increased. Additionally, in 3 of 7 studies, VitD supplementation led to an increase in CD4+ T cell count, although its effect on viral load was inconclusive since most patients were on cART. Similarly, previous evidence from our laboratory has shown that VitD can reduce the infection of CD4+ T cells in vitro. The effect of VitD supplementation on other HIV-associated conditions, such as cardiovascular diseases, dyslipidemia or hypertension, warrants further exploration. Currently, the available evidence suggests that there is a potential role for VitD supplementation in people living with HIV-1, however, comprehensive studies are required to define an adequate supplementation protocol for these individuals.
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2.
Lipid Abnormalities in Persons Living With HIV Infection.
Waters, DD, Hsue, PY
The Canadian journal of cardiology. 2019;(3):249-259
Abstract
Lipid abnormalities are prevalent among persons living with HIV infection and contribute to increasing the risk of cardiovascular events. Antiretroviral therapy (ART) is associated with lipid abnormalities, most commonly hypertriglyceridemia, but also increases in low-density lipoprotein cholesterol and total cholesterol. Different classes of ART, and different drugs within classes, have differing effects on lipid levels, but in general newer drugs have more favourable effects compared with older ones. Low-level inflammation and chronic immune activation act on lipids through a variety of mechanisms to make them more atherogenic. As a consequence, risk is higher than would be expected for any given cholesterol level. Clinical outcome trials of cholesterol-lowering therapies have not yet been completed in people living with HIV, so that treatment decisions depend on extrapolation from studies in uninfected populations. Traditional risk assessment tools underestimate cardiovascular risk in individuals with HIV. Statins are the mainstay of lipid-lowering drug treatment; however, drug-drug interactions with ART must be considered. Simvastatin and lovastatin are contraindicated in patients taking protease inhibitors, and the dose of atorvastatin and rosuvastatin should be limited to 40 mg and 10 mg/d with some ART combinations. Switching from older forms of ART to lipid-friendly newer ones is a useful strategy as long as virologic suppression is maintained, but adding a statin lowers low-density lipoprotein cholesterol more effectively. Studies indicate that lipid abnormalities are not treated as aggressively in individuals living with HIV as they are in uninfected people, making this an opportunity to improve care.
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3.
Treatment of Central Nervous System Manifestations of HIV in the Current Era.
Handoko, R, Spudich, S
Seminars in neurology. 2019;(3):391-398
Abstract
Treatment of neurological, neurocognitive, and neuropsychiatric impairment in the setting of human immunodeficiency virus (HIV) infection remains a complex problem, given several possible mechanisms of pathogenesis. The etiology must be determined based on clinical judgment and objective evidence, including cerebrospinal fluid (CSF) data from lumbar puncture and neuroimaging information from magnetic resonance imaging, when available and indicated. Other neuroinfectious etiologies must be ruled out, including central nervous system (CNS) opportunistic infections. HIV replication in the CNS (including CSF escape) should be evaluated for and excluded. If CSF HIV is detected, we recommend a treatment switch to antiretrovirals (ARVs) targeted to address any CSF HIV resistance mutations identified, or empiric treatment intensification using ARVs with high CNS penetration. If CSF HIV is not detected, treatment intensification with CCR5 inhibitors may be considered as an adjunct to reduce neuroinflammation. Finally, the current ARV regimen must be examined for possible neurotoxicity. Efavirenz has been well-recognized for its neuropsychiatric adverse effects and potential for causing sleep disturbances. Similar concerns have recently been raised with integrase inhibitors, especially dolutegravir and raltegravir, although further studies are needed to determine the risks for clinically relevant neuropsychiatric side effects from these medications, given their overall high potency and proven success in treating systemic HIV.
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4.
Long-acting or extended-release antiretroviral products for HIV treatment and prevention in infants, children, adolescents, and pregnant and breastfeeding women: knowledge gaps and research priorities.
Nachman, S, Townsend, CL, Abrams, EJ, Archary, M, Capparelli, E, Clayden, P, Lockman, S, Jean-Philippe, P, Mayer, K, Mirochnick, M, et al
The lancet. HIV. 2019;(8):e552-e558
Abstract
Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10-19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.
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5.
Liver Disease in Human Immunodeficiency Virus Infection.
Oikonomou, KG, Tsai, E, Sarpel, D, Dieterich, DT
Clinics in liver disease. 2019;(2):309-329
Abstract
Liver disease in human immunodeficiency virus (HIV) remains a main cause of morbidity and mortality. Liver-related morbidity and mortality can be caused by multiple etiologic factors, including opportunistic infections, direct and indirect effects of antiretrovirals, direct and indirect effects of HIV, and viral hepatitides. These factors present with varied liver pathophysiologic mechanisms that lead to abnormalities in liver enzymes and synthetic function test, followed by distinct clinical presentations. This article elucidates the direct effects on HIV in the liver and explores the diagnostic and management challenges in patients with HIV in the era of highly active antiretroviral treatment.
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6.
Non-Alcoholic Fatty Liver Disease in Patients with HIV Infection.
Papagianni, M, Tziomalos, K
AIDS reviews. 2018;(3):171-173
Abstract
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with HIV infection and appears to be more severe than in HIV-uninfected patients. Both metabolic (e.g., obesity and insulin resistance) and HIV-related factors (e.g., antiretroviral treatment and inflammation) play a role in the pathogenesis of NAFLD in this population. Accordingly, all patients with HIV infection should be evaluated for the presence of NAFLD. Ultrasound is the first-line diagnostic procedure, but non-alcoholic steatohepatitis has to be diagnosed with liver biopsy. However, non-invasive methods, including serological markers and transient elastography, might also be useful in this population. Lifestyle changes represent the cornerstone of treatment. Bariatric surgery, pioglitazone, and vitamin E can be considered in patients with significant fibrosis or at high risk for progression of NAFLD, including those with type 2 diabetes mellitus, metabolic syndrome, elevated transaminases, or pronounced necroinflammation. However, there are no studies that evaluated the safety of efficacy of diet, exercise, or pharmacotherapy in this population. Therefore, research is needed to identify safe and effective pharmacological treatments for NAFLD in patients with HIV infection.
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7.
Gut microbial diversity in HIV infection post combined antiretroviral therapy: a key target for prevention of cardiovascular disease.
El-Far, M, Tremblay, CL
Current opinion in HIV and AIDS. 2018;(1):38-44
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Abstract
PURPOSE OF REVIEW Although the HIV-infected population is living longer and getting older under current treatment regimens, significant challenges arise for health management as the infection is associated with various premature aging phenotypes, particularly increased incidence of cardiovascular diseases (CVDs). Here we review the current understanding of HIV-related gut dysbiosis in association with CVD and advances in clinical trials aiming to restore gut microbial diversity. RECENT FINDING Identification of a unique signature for gut dysbiosis in HIV infection between different cohorts remains challenging. However, low diversity of microbiota combined with the outgrowth of pathogenic bacterial species together with dysregulated metabolic pathways have been linked to compromised gut immunity, bacterial translocation and systemic inflammation, hence higher CVD risk among different cohorts. Data from recent clinical trials aiming to evaluate the tolerability and efficacy of probiotics in treated HIV+ patients are promising and support a significant increase in microbiota diversity and reduction of systemic inflammation. However, the impact of these microbial and immunological corrections on the prevalence of CVD in HIV+ patients remains unclear. SUMMARY Positive immunological outcomes following enrichment of the gut microbial diversity have been documented, and further trials are in progress to evaluate the range of patients, with different immunological backgrounds, who might benefit from these treatments.
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Dietary supplement interactions with antiretrovirals: a systematic review.
Jalloh, MA, Gregory, PJ, Hein, D, Risoldi Cochrane, Z, Rodriguez, A
International journal of STD & AIDS. 2017;(1):4-15
Abstract
Many patients who take antiretroviral drugs also take alternative therapies including dietary supplements. Some drug-supplement combinations may result in clinically meaningful interactions. We aimed to investigate the evidence for dietary supplement interactions with antiretrovirals. A systematic review was conducted using multiple resources including PubMed, Natural Medicine Comprehensive Database, The Review of Natural Products, and Google Scholar. All human studies or case reports evaluating an interaction between a dietary supplement and an antiretroviral were selected for inclusion. Twenty-eight pharmacokinetic studies and case-series/case reports were selected for inclusion. Calcium carbonate, ferrous fumarate, some forms of ginkgo, some forms of garlic, some forms of milk thistle, St. John's wort, vitamin C, zinc sulfate, and multivitamins were all found to significantly decrease the levels of selected antiretrovirals and should be avoided in patients taking these antiretrovirals. Cat's claw and evening primrose oil were found to significantly increase the levels of antiretrovirals and patients should be monitored for adverse effects while taking these dietary supplements with antiretrovirals. This systematic review shows the importance of screening all human immunodeficiency virus patients for dietary supplement use to prevent treatment failure or adverse effects related to an interaction.
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Challenges in the Elimination of Pediatric HIV-1 Infection.
Luzuriaga, K, Mofenson, LM
The New England journal of medicine. 2016;(8):761-70
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10.
Lipid Abnormalities and Inflammation in HIV Inflection.
Funderburg, NT, Mehta, NN
Current HIV/AIDS reports. 2016;(4):218-25
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Abstract
Infection with the human immunodeficiency virus (HIV), and subsequent treatment with antiretroviral therapy (ART), is often associated with perturbations in lipid profiles. Furthermore, persistent inflammation, in spite of suppression of viral replication by ART, likely contributes to modifications in lipid composition and function, exacerbating risk for development of cardiovascular disease (CVD). Increased levels of several pro-inflammatory lipid species, including oxidized low-density lipoprotein (LDL) and high-density lipoprotein (HDL), have been measured in HIV-infected persons and are associated with markers of immune activation. The mechanisms linked to this bidirectional relationship in which inflammation increases lipid levels and promotes their modification, and these modified lipid species perpetuate inflammatory processes, require further investigation. Treatment with statins and other lifestyle modifications, including improvement in dietary intake and exercise, are critical to reducing CVD risk. Well-designed clinical trials that take into account the complex relationships among lipids and inflammation within persons infected with HIV need to be considered.