AIDS | HIV  - OXYMED HYPERBARIC OXYGEN THERAPY TIER 2

Vision Projects

  • Papua New Guinea

'to establish HBO as an adjunctive care for children & adults suffering the effects of AIDS. It is our vision that mobile shipping containers housing small multiplace chambers can be specifically located via truck or helicopter into remote regions to assist communities impacted by the devastating effects of AIDS.'

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy?

Mediators Inflamm. 2013;2013:484378. doi: 10.1155/2013/484378. Epub 2013 Dec 19.

Kumar A1, Abbas W1, Herbein G2.

Author information

  • 1Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France.

  • 2Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France ; Department of Virology, University of Franche-Comte, Hôpital Saint-Jacques, 2 Place Saint-Jacques, 25030 Besançon Cedex, France.

 

Abstract

Tumor necrosis factor (TNF) and TNF receptors (TNFR) superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways.

Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.

 

 

For More Anti Tumour Necrosis Therapies

  • Hyperbaric Oxygen Therapy is an inhibitor of Tumour Necrosis Factor and other inflammatory cytokines.

  • Hyperbaric oxygen therapy (HBO; pO2 = 760 mmHg) has been successfully used against bacterial and fungal infections and as an adjunct therapy in surgeries [17][19]. In addition, reports have recently shown that HBO therapy transiently suppresses the inflammatory process of ischemic wounding and trauma [20], [21]. Indeed, immunological analyses have revealed that HBO therapy significantly decreases the levels of TNF-α and IL-1β secreted by monocytes and macrophage collected from rats or from human peripheral blood after stimulation with LPS [22], [23]. In an experimental model for ischemia, HBO reduces immunocompetent cell sequestration and the synthesis of TNF-α [24]; probably by decreasing ICAM-1 expression levels [25].

  • Moreover, HBO reduces the expression of the cyclooxygenase-2 (COX-2) mRNA, an enzyme involved in inflammation, and the hypoxia-inducible factor-1α (HIF-1α), a transcriptional factor associated with low oxygen concentrations [26], [27].

  • HBO therapy has been used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis, due to its capacity to decrease cerebral edema and brain infarction while maintaining BBB integrity, reducing neuronal death and improving blood flow in damaged areas of the brain [28].

  • In summary, HBO may have beneficial effects against HIV immunosupression.

  • Administration of pressurized oxygen down-regulates IFN-γ, TNF-α and IL-10 cytokine expression and the migration to the brain of T lymphocytes, preventing BBB breakdown.

 

 

Can TNF inhibitors be used in HIV-positive patients?

Ask the Expert

http://www.hss.edu/professional-conditions_tnf-inhibitors-used-in-hiv-positive-patients.asp

Dee Dee Wu, MD Rheumatology Fellow Hospital for Special Surgery
 

The literature on the clinical efficacy and safety of anti-TNF agents in HIV-infected individuals is extremely limited, with only a few anecdotal case reports to guide us. However, the theoretical risks and benefits of anti-TNF therapy in this immunosuppressed population can be extrapolated from a number of in vitro and in vivo studies investigating the role of TNF-a in HIV infection, and the effects of TNF blockade on HIV RNA levels and CD4 counts.

TNF-a is a pro-inflammatory cytokine that functions as a central mediator of inflammation and immune regulation. Not surprisingly, given its role in host defense against viral infections, TNF-a levels have been found to be elevated in HIV+ patients,[1],[2] reflecting immune system activation. However, a number of in vitro studies have demonstrated deleterious effects of TNF-a, thereby implicating it in the pathogenesis of HIV. TNF-a has been shown to increase destruction of infected CD4+ lymphocytes[3] and up-regulate HIV replication in HIV-infected cells in vitro,[4],[5],[6] while anti-TNF-a antibodies have been shown to suppress HIV-1 production in chronically infected T lymphocytic cell lines[7]. Moreover, monocytes exposed to HIV proteins can be induced to produce TNF-a,[8] thus linking overproduction of TNF-a with HIV replication, and potentially HIV disease progression.

Clinically, TNF-a levels have been positively correlated with HIV-RNA levels,[9] and down-regulation of TNF-a has been demonstrated upon initiation of highly active antiretroviral therapy (HAART). Persistence of TNF-a after initiation of HAART therapy has also been suggested to correlate with virologic and immunologic treatment failure as well (defined as detectable HIV RNA after 52 weeks of therapy and significant decrease in CD4 lymphocytes, respectively).[10] Specific effects of TNF blockade on HIV RNA and CD4 counts have been studied in a number of clinical trials using thalidomide and pentoxifylline, weak inhibitors of TNF-a production, as well as etanercept and cA2, a chimeric humanized monoclonal antibody against TNF-a.

Wallis et al[11] found that pentoxifylline decreased plasma HIV RNA levels in a group of untreated HIV+ patients with pulmonary TB, but had no proven effect on TNF-a, CD4 cell count or patient survival. In contrast, Jacobson et al[12] found that thalidomide unexpectedly increased HIV RNA and plasma concentrations of TNF-a.

Sha et al[13] studied the effect of etanercept on TNF-a and other cytokines in HIV-infected patients on HAART receiving IL-2 injections (previously shown to increase CD4 lymphocytes when administered in HIV patients with CD4 counts >200/mm3). Etanercept was given as a single 10 mg intravenous infusion, and was not found to have a significant effect on CD4 count or viral load, although all patients at baseline started out with undetectable or low-level viremia. The effect on TNF-a bioactivity could not be assessed in this study.

Lastly, Walker et al[14] investigated the effect of cA2 on levels of TNF-a, CD4 cells and HIV RNA in six HIV+ patients with CD4 counts below 200/mm3. Two infusions of 10mg/kg were given 14 days apart, resulting in only transient decreases in TNF-a levels, but no significant effect on CD4 cell counts or plasma HIV RNA levels over the 42 day period.

Thus far, there have only been two case reports on the use of anti-TNF agents in HIV+ patients with rheumatic disease. Aboulafia et al[15] reported the use of etanercept, 25 mg SQ twice weekly, in a 45 year old HIV-infected male on HAART who developed severe skin disease and disabling psoriatic arthritis. The patient had at baseline a CD4 count of 20/mm3, viral load 14,000 copies/mL, ESR 125, and radiographs of hands and feet that were consistent with psoriatic arthropathy. Within three weeks of initiating etanercept, the patient had dramatic improvement in skin and joint manifestations, and his CD4 count and HIV viral load remained stable throughout the six month treatment course. However, his clinical course was complicated by recurrent polymicrobial bacterial infections, both while on therapy and in the subsequent four months after therapy had been discontinued, which ultimately led to the patient's demise.

Gaylis[16] reported the safe use of infliximab (3mg/kg every 6-7 weeks) in a 41 year old HIV+ male on HAART with Reiter's syndrome refractory to corticosteroids and methotrexate. The patient had at baseline a CD4 count of 770 cells/mm3 and a viral load of <500 copies/mL. With infliximab, he experienced significant resolution of all symptoms attributed to his Reiter's syndrome, and was able to discontinue use of daily corticosteroids. No adverse events were reported during the 18 months that the patient received infusions, and the pt's CD4 count and viral load remained stable.

Because TNF-a plays an important role in host defense against microorganisms, there is obviously concern that TNF blockade, even in immunocompetent hosts, might result in an increased frequency or severity of infections. Reactivation of tuberculosis (TB) is a well-recognized complication, and this specific issue has been indirectly addressed in a phase 1 study investigating the role of etanercept as adjunctive therapy for HIV+ patients with pulmonary TB.[17] 16 HIV+ patients with CD4 counts >200/mm3 and active pulmonary TB were treated with etanercept 25 mg subcutaneously twice weekly for a total of eight doses, in conjunction with TB therapy. When compared to controls with similar CD4 counts, patients receiving etanercept were, on average, able to develop negative sputum cultures more rapidly (p=0.05). However, two patients had increases in sputum AFB counts, warranting discontinuation of therapy. Etanercept was discontinued in a third patient due to a rise in HIV RNA and worsening of cough and dyspnea, ultimately attributed to pulmonary embolism. Of the remaining patients, there were no statistically significant differences in CD4 counts or plasma HIV RNA levels between the treatment and control groups. The authors concluded that etanercept could be safely administered during the initial treatment of pulmonary TB. (This is discussed in the Ask the Expert response to: In RA patients unresponsive to several DMARDs but who are PPD+ although the chest X-ray is negative, how long should INH prophylaxis be maintained before initiating an anti-TNF agent? Is anakinra safe to use in patients with a positive PPD?)

  • In summary, based on the data from limited case reports and a number of in vitro and in vivo experiments, it is reasonable to conclude that anti-TNF agents can be used with great caution in HIV+ patients with significant morbidity from a TNF-a-mediated illness. Other patient factors that may influence therapy include pre-treatment CD4 counts, HIV RNA levels, and coexisting hepatitis B and C infection. If anti-TNF therapy is initiated, strict adherence to current guidelines,[18] such as PPD placement and pneumococcal vaccination, should be observed to minimize potential infectious complications.

 

Mediators Inflamm. 2013;2013:484378. doi: 10.1155/2013/484378. Epub 2013 Dec 19.

TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy?

Kumar A1, Abbas W1, Herbein G2.

Author information

  • 1Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France.

  • 2Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France ; Department of Virology, University of Franche-Comte, Hôpital Saint-Jacques, 2 Place Saint-Jacques, 25030 Besançon Cedex, France.

Abstract

Tumor necrosis factor (TNF) and TNF receptors (TNFR) superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.

 

Joint Bone Spine. 2013 Jul;80(4):426-8. doi: 10.1016/j.jbspin.2013.01.002. Epub 2013 Mar 1.

Successful use of antitumor necrosis factor-alpha biological therapy in managing human immunodeficiency virus-associated arthritis: three case studies from Saudi Arabia

Almoallim H1, Jali I, Wali G.

Author information

  • 1Department of Medicine, Medical College, Umm Alqura University, PO Box 1821, 21441 Jeddah, Saudi Arabia. hanialmoallim@hotmail.com

Abstract

Arthralgic disorders involving various rheumatic manifestations are commonly observed in HIV patients. Available therapies for HIV-associated rheumatic syndromes include non-steroidal anti-inflammatory drugs for pain management, disease-modifying antirheumatic drugs (e.g., methotrexate), and antitumor necrosis factor-alpha therapies. However, treatment of HIV-associated arthritis can be challenging, particularly in patients with co-infections like hepatitis viruses, and therapeutic strategies are not well defined. Here, we present three case reports on the use of antitumor necrosis factor-alpha agents for HIV-associated arthritis. We managed three cases of HIV-associated arthritis following initial presentation. All patients were on highly active antiretroviral therapy with stable HIV loads and CD4(+) cell counts. Data were reported for treatment of inflammatory arthritis using 5 months of etanercept followed by adalimumab for case 1, and 12 months of etanercept for case 2. In case 3, reactive arthritis was treated with 5 months of etanercept followed by adalimumab. In all three cases, significant improvement or resolution of arthritis was achieved following treatment with antitumor necrosis factor-alpha therapies. Moreover, these case studies demonstrated the safe and effective use of antitumor necrosis factor-alpha agents in HIV patients with hepatitis B and/or C virus co-infection. Our results indicate that antitumor necrosis factor-alpha therapies can be successfully used for HIV-infected patients with stable HIV loads and CD4(+) lymphocyte counts.

 

ScientificWorldJournal. 2013 Oct 1;2013:986429. doi: 10.1155/2013/986429. eCollection 2013.

Arzanol, a potent mPGES-1 inhibitor: novel anti-inflammatory agent

Kothavade PS1, Nagmoti DM, Bulani VD, Juvekar AR.

Author information

  • 1Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400 019, India.

Abstract

Arzanol is a novel phloroglucinol α -pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NF κB activation, HIV replication in T cells, releases of IL-1 β , IL-6, IL-8, and TNF-α , and biosynthesis of PGE₂ by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects

 

Clin Vaccine Immunol. 2013 May;20(5):761-4. doi: 10.1128/CVI.00081-13. Epub 2013 Mar 6.

Septic shock after seasonal influenza vaccination in an HIV-infected patient during treatment with etanercept for rheumatoid arthritis: a case report

De Nardo P1, Bellagamba R, Corpolongo A, Gentilotti E, Taglietti F, Rosati S, Galeazzi M, Sebastiani GD, Quinti I, Nicastri E.

Author information

Abstract

Anti-tumor necrosis factor alpha (anti-TNF-α) is used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure that occurred after etanercept initiation and influenza vaccination in an HIV-infected woman with rheumatoid arthritis.

 

Med Hypotheses. 2000 Sep;55(3):232-8.

HIV: reactive oxygen species, enveloped viruses and hyperbaric oxygen

Baugh MA.

Author information

  • BaroAntiviral, San Diego, California 92103, USA.

Abstract

This paper demonstrates that there are many examples in the literature of contradictory data concerning reactive oxygen intermediates (ROIs), responsible for producing cellular oxidative stress (OS), and their enhancement or diminution of viral replication. Nevertheless, ROIs repeatedly have been shown to be virucidal against enveloped-viruses, like the human immunodeficiency virus (HIV). Hyperbaric oxygen therapy (HBOT) increases the production of ROIs throughout the body, leaving no safe harbor for the virus to hide outside the genome. This technique already has been tried on acquired immune deficiency syndrome (AIDS) patients, with exciting results. Historically, the biggest setback to demonstrating HBO's antiviral effects has been the investigator's folly of studying non-enveloped viruses or failing to initiate ROI production. ROIs specifically attack areas of unsaturation occurring in the polyunsaturated fatty acids of cell membranes and viral envelopes. Moreover, it consistently has been shown that a peroxidized viral envelope breaches, and a breached viral envelope causes viral disintegration.

 

J Assoc Nurses AIDS Care. 1999 Sep-Oct;10(5):42-9.

A review of fatigue in people with HIV infection

Barroso J.

Author information

  • University of North Carolina at Chapel Hill, School of Nursing, USA.

Abstract

Fatigue is often cited by clinicians as a debilitating symptom suffered by the many who are infected with HIV. This article provides a review of HIV-related fatigue, including research on possible physiological causes such as anemia, CD4 count, impaired liver function, impaired thyroid function, and cortisol abnormalities. Psychological causes of fatigue, particularly depression, are reviewed as well. Measurement issues, such as the use of inappropriate tools, the problem of measuring the presence or absence of fatigue, and the use of tools developed for other groups of patients, are reviewed. The need for a comprehensive fatigue tool that is appropriate for people with HIV is discussed. Current treatment research, including thyroid replacement, hyperbaric oxygen, and dextroamphetamine, is presented. Finally, the implications for further research, including the need for qualitative studies to learn more about the phenomenon, develop an instrument to measure fatigue, and examine variables together to get a complete picture of this complex concept, are reviewed.

 

J Assoc Nurses AIDS Care. 1996 Jan-Feb;7(1):43-5.

HIV antiviral effects of hyperbaric oxygen therapy

Reillo MR1, Altieri RJ.

Author information

  • 1Lifeforce Hyperbaric Medical Clinic, Baltimore, MD, USA.

Abstract

Researchers have speculated that hyperbaric oxygen (HBO) therapy has an antiviral effect in HIV infection. To determine HBO's antiviral effect, the authors performed ex vivo and in vivo quantitative assays on HIV-infected plasma and peripheral blood mononuclear cells (PBMCs) at baseline and after treatment. The authors also HBO-treated uninfected PBMCs and then exposed them to HIV at ambient pressure. HIV viral load was decreased in the infected cells, and few viruses entered uninfected PBMCs exposed to HBO. The results of this study support the theory that HBO has an antiviral effect.

J Assoc Nurses AIDS Care. 1993 Jul-Sep;4(3):33-8.

Hyperbaric oxygen therapy for the treatment of debilitating fatigue associated with HIV/AIDS

Reillo MR.

Author information

  • Maryland Medical Center, Bethesda.

Abstract

Twenty-five HIV-infected patients underwent hyperbaric oxygen therapy to determine the treatment's effectiveness in relieving the debilitating fatigue associated with HIV/AIDS and its effect on immunologic function. Patients were treated with 100% oxygen at two atmospheres of absolute pressure three times per week for two months, then two times per week on an ongoing basis. Laboratory markers were assessed monthly.

  • All patients experienced relief of debilitating fatigue within one month of hyperbaric oxygen therapy. It was concluded that hyperbaric oxygen therapy is an effective adjunctive treatment in the medical management of HIV/AIDS. Laboratory markers, clinical significance, nursing implications, and cost-effectiveness of hyperbaric oxygen therapy are discussed.

Prevalence of Sexually Transmitted Infections in PNG

Recent published estimates suggest Papua New Guinea (PNG) has among the highest adult HIV prevalence in the Asia-Pacific region estimated at 1.28% among people aged 15–49 years in 2007, although more recent estimates suggest national prevalence may be closer to 1.0%. The epidemic is primarily linked to heterosexual transmission, and exhibits substantial geographic heterogeneity, with over half the reported HIV diagnoses coming from the capital, Port Moresby; 20% from Western Highlands; and 10% from Morobe Province.

Modelling projections suggest that by 2025, adult HIV prevalence could be as high as 10% and around 300,000–400,000 people will have died from AIDS-related illness.

 

Innovative strategies for HIV prevention, treatment and care are urgently needed to address this complex public health issue in a country with unparalleled geographical, linguistic and cultural diversity.