Connecting the Dots: Could Microbial Translocation Explain Commonly Reported Symptoms in HIV Disease?

Wilson, Natalie; Vance, David E.; Moneyham, Linda; Raper, James L.; Mugavero, Michael J.; Heath, Sonya L.; Kempf, Mirjam-Colette

doi:10.1016/j.jana.2014.07.004

Cited by 11 publications

(12 citation statements)

References 58 publications

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“…(33) Despite the changes in management of the disease and its treatment, fatigue persists as a burdensome symptom among PLWH. The etiology of fatigue is multifactorial and has been associated with various physiologic and psychological factors including being attributed to the long-term effects of inflammation from the virus,(63, 64) whose mechanism is still not well-understood.…”

Section: Discussionmentioning

confidence: 99%

Racial and socioeconomic disparities in the symptom reporting of persons living with HIV

et al. 2018

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Persons living with HIV (PLWH) today can survive decades with the disease, making the symptom experience much more relevant to their lifestyle and health outcomes. The goal of the research reported here was to assess the symptom reporting of PLWH in the Unites States (US) in the combined antiretroviral therapy (cART) age of the epidemic. We conducted an anonymous online survey of symptomatic PLWH in the US and asked participants to report the frequency and intensity of 28 frequently occurring symptoms in the past 30 days. The relationship between symptom reporting and demographic factors was investigated using the adaptive least absolute shrinkage and selection operator (LASSO) method. Fatigue was the most frequently reported symptom in our study population. Those with the lowest income were more likely to report more burdensome symptoms. In comparison to other racial and ethnic groups, Black non-Hispanic participants were significantly more likely to report a lower symptom burden score for fatigue, depression, muscle aches, anxiety, difficulties with memory and concentration. There were no racial/ethnic differences in the burden of the symptoms related to sleep or neuropathy. Findings from this study present new evidence on the symptom reporting of PLWH in the US. Neuropathy continues to be a pervasive neurological symptom with no difference noted between racial/ethnic groups.

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Section: Discussionmentioning

confidence: 99%

Racial and socioeconomic disparities in the symptom reporting of persons living with HIV

et al. 2018

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“…These symptoms were likely related to long-term cART; however, newer therapies have lower side-effect profiles. Other explanations included long-term effects of inflammation (Wilson et al, 2014). Fatigue (Klimas, Broderick, & Fletcher, 2012), neuropathy (Harezlak et al, 2011; Zheng et al, 2011), obesity (Koethe et al, 2013), and cognitive decline including memory loss (Ancuta et al, 2008; Deeks, 2011; Kamat et al, 2012) have been associated with inflammation.…”

Section: Discussionmentioning

confidence: 99%

Identifying Symptom Patterns in People Living With HIV Disease

Wilson¹,

Azuero²,

Vance³

et al. 2016

Journal of the Association of Nurses in AIDS Care

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Symptoms guide disease management, and patients frequently report HIV-related symptoms, but HIV symptom patterns reported by patients have not been described in the era of improved antiretroviral treatment. The objectives of our study were to investigate the prevalence and burden of symptoms in people living with HIV and attending an outpatient clinic. The prevalence, burden, and bothersomeness of symptoms reported by patients in routine clinic visits during 2011 were assessed using the 20-item HIV Symptom Index. Principal component analysis was used to identify symptom clusters and relationships between groups using appropriate statistic techniques. Two main clusters were identified. The most prevalent and bothersome symptoms were muscle aches/joint pain, fatigue, and poor sleep. A third of patients had seven or more symptoms, including the most burdensome symptoms. Even with improved antiretroviral drug side-effect profiles, symptom prevalence and burden, independent of HIV viral load and CD4+ T cell count, are high.

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“…Both IFN-γ and LPS enhance SMX adduct formation within dendritic cells in vitro , (Lavergne et al, 2009) and concentrations of serum IFN-γ, plasma LPS, and plasma sCD14, which is secreted in response to circulating LPS complexes, (Wilson et al, 2014) are increased in some HIV-infected patients (Brenchley et al, 2006; Watanabe et al, 2010; Wilson et al, 2014). In our study, median circulating IFN-γ concentrations were not significantly different in SIV-infected macaques (1.8 pg/ml) compared to non-infected controls (0.0 pg/ml).…”

Section: Discussionmentioning

confidence: 99%

“…LPS was quantified with the QCL-1000™ Endpoint Chromogenic LAL Assays (Lonza; limit of quantitation 0.1 EU/ml) in sera diluted with endotoxin-free water. Plasma sCD14, which is released in response to circulating LPS complexes, (Wilson et al, 2014) was quantified with a commercially available sCD14 Quantikine ELISA Kit (R&D Systems).…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity of trimethoprim/sulfamethoxazole in a macaque model of HIV infection

Wong

Rakasz²,

Gasper

et al. 2016

Toxicology

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Background Sulfonamide hypersensitivity has a high incidence in HIV infection and correlates with low CD4+ counts, but the mechanisms are not understood. The aims of this study were to determine whether trimethoprim/sulfamethoxazole (TMP/SMX) led to SMX adduct formation, immunogenicity, or signs of drug hypersensitivity in SIV-infected rhesus macaques, and whether differences in antioxidants, pro-inflammatory mediators, or SMX disposition were predictive of drug immunogenicity. Methods Nine macaques chronically infected with SIVmac239 and 7 non-infected controls were studied. Baseline blood ascorbate, glutathione, IFN-γ, LPS, sCD14, and cytochrome b5 reductase measurements were obtained, macaques were dosed with TMP/SMX (120 mg/kg/day p.o. for 14 days), and SMX metabolites, lymph node drug adducts, drug-responsive T cells, and anti-SMX antibodies were measured. Results Four of 9 of SIV-positive (44%), and 3 of 7 SIV negative (43%) macaques had drug-responsive T cells or antibodies to SMX. Two macaques developed facial or truncal rash; these animals had the highest levels of lymph node drug adducts. Antioxidants, pro-inflammatory mediators, and SMX metabolites were not predictive of drug immunogenicity; however, the Mamu DRB1*0401/0406/0411 genotype was significantly over-represented in immune responders. Conclusions Unlike other animal models, macaques develop an immune response, and possible rash, in response to therapeutic dosages of TMP/SMX. Studying more animals with CD4+ counts < 200 cells/µl, along with moderately restricted ascorbate intake to match deficiencies seen in humans, may better model the risk of SMX hypersensitivity in HIV-infection. In addition, the role of Mamu-DRB1 genotype in modeling drug hypersensitivity in retroviral infection deserves further study.

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Connecting the Dots: Could Microbial Translocation Explain Commonly Reported Symptoms in HIV Disease?

Cited by 11 publications

References 58 publications

Racial and socioeconomic disparities in the symptom reporting of persons living with HIV

Racial and socioeconomic disparities in the symptom reporting of persons living with HIV

Identifying Symptom Patterns in People Living With HIV Disease

Immunogenicity of trimethoprim/sulfamethoxazole in a macaque model of HIV infection

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