The safety and efficacy of Faramir in treating HIV+ patients Mino Mohrez1,2, Ahmad Alinaghi1*, Ibrahim Farzam2 1 The Department of Infectious & Tropical Diseases, Imam Khomeini Hospital, Keshavarz Blvd, Tehran, Iran 2 Iranian research center for HIV/AIDS(IRCHA) Abstract Background: Patients suffering from HIV virus are currently treated by several antivirus agents, but unfortunately these drugs can not eliminate the virus and give the patient real treatment. A number of medical researchers and practitioners have called for new drugs to combat HIV. The present investigation is designed to test the efficacy of Faramir. Faramir is made of natural elements. Clinical investigations of Faramir in HIV treatment were made on seven patients with AIDS. The Subjects received orally administered Faramir for 180 days. Methods: Faramir was used three times daily for six months in seven HIV+ patients. The effect or possible side effects were observed 3 months after treatment. Blood sample assessments were conducted for the four dependent measures used in this study: HIV viral loads, CD4 levels, T-cell counts and white blood cell counts. Other data such as body temperature, fatigue levels and standard clinical diagnostics were collected for general appraisals of patient health and treatment efficacy. Results: All the subjects experienced a significant drop in HIV viral loads. The viral load became undetectable (˂150 μl) in three patients with substantial improvement in their clinical condition. One patient’s viral load dropped from 7950 copies/mL to 114 copies/mL. Faramir had no effect on CD4 level in short term, but the number of CD4 increased as the immune system improved. Conclusions: Faramir decreases the number of HIV virus in body. The immune system improves after therapy, as the number of virus decreases in the body. Faramir has not major immunological or allergic reactions in all patients. Keywords: HIV, viral load, CD4 level, Faramir Background Human immunodeficiency virus (HIV) affects human immune system and causes a disease named acquired immune deficiency syndrome, or AIDS. The syndrome makes the person much more susceptible to common infections like tuberculosis as well as opportunistic infections and tumors, often by which human life is threatened and lost. It has been estimated that acquired immune deficiency syndrome (AIDS) has killed more than 25 million people since it was first recognized in 1981(ref 1). According to a consensus made in year 2009, globally there are approximately 33.3 million people living with the human immunodeficiency virus (ref 2). There is not currently any cure for AIDS or vaccines to prevent this disease. The treatment protocols, generally considered to be most effective, typically involve two or three different anti-retroviral drugs used in combination. The use of antiretroviral drugs has reduced the morbidity and mortality associated with AIDS, however, a significant number of HIV infections have become resistant to antiretroviral treatment (ref 3). Moreover, these medications are expensive and have side effects. The cost and the politics of access to antiretroviral therapies, have encouraged the use of other treatment approaches. This study is focused on using Faramir, a combination of natural elements registered under the Iranian registry of clinical trials, for HIV infections.The efficacy and safety of Faramir to treat HIV+ patients are investigated. Methods The analysis included patients with CD4 count between 250cells/mm3 and 600cells/mm3 ( 200cells/mm3 ≤ CD4 T-cell count ≤ 600cells/mm3) , viral load more than 1000(plasma HIV-1 RNA ≥ 1000 copies/ml), age between 18 to 65, both males and females, plt ˃ 50000, hb ˂ 8, ALT and AST ˂ 3, Creatinine ˂1.5, adequate hematologic function(platelates ≥ 50x103/μl, hemoglobin ≥ 8.0g/dl, absolute neutrophil count ≥ 1000/μl), adequate liver function(transaminase ≤ 3x normal) Patients were excluded if they had received growth hormone within 30 days before entry into the study. Also excluded were pregnant or breast-feeding women, as were patients with active substance abuse, hepatitis B and C surface antigen, if they required maintenance therapy for an opportunistic infection, or if they had received investigational or immunomodulatory drugs within 180 days before entry into the study. HSV patients and patients using immunosuppressive medications, and also those with CD4˂200cells/mm3 were excluded. Creatinine clearance less than 50ml/min tested by Cockroft-Gault equation (ref 4) was also in among exclusion criteria. Faramir, under the number of IRC201112124076N6 (Iranian registry of clinical trials), was used as an orally administered 330 mg/tablet, three times daily for six months in seven HIV+ patients. HIV ELISA/Western blot tests were used in this clinical trial to diagnose HIV+ patients. . The effect or possible side effects were observed 3 months after treatment. Blood sample assessments were conducted for the four dependent measures used in this study: HIV viral loads, CD4 levels, T-cell counts and white blood cell counts. Other data such as body temperature, fatigue levels and standard clinical diagnostics were collected for general appraisals of patient health and treatment efficacy. Toxicity tests were examined on 3 groups of Male rats with mean weight of 160 gram. Results The effect of Faramir on viral load showed a decrease number of virus in the bodies of 6 patients. The viral load became undetectable (˂150 copies/mL) in three subjects (patient's codes 2, 4 and 6, Fig.1). One patient’s viral load dropped from 7950 copies/mL to 114 copies/ mL ( patient's code 2, Fig.1). Faramir had no effect on CD4 level in a short term and the CD4 count showed fluctuation within 6 months of therapy. However, the number of CD4 increased in a longer time (patient's codes 2, 5 and 6, Fig.2). CD4 increase was predominant in one patient; (patient' code 2, the CD4 level increased from 603cells/mm3 to 1310cells/mm3). In the toxicity tests performed on the three groups of male rats, oral administration up to 2 gram/kg showed no poisonous effect or mortality after 72 hrs. (Fig.3). Discussion Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a disease of the human immune system. Following initial infection, a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms. As the infection progresses, it interferes more and more with the immune system, making the person much more susceptible to common infections like tuberculosis, as well as opportunistic infections and tumors that do not usually affect people who have healthy immune systems. The late symptoms of the infection are referred to as AIDS. This stage is often complicated by an infection of the lung known as pneumocystis pneumonia, severe weight loss, a type of cancer known as Kaposi's sarcoma, or other AIDS-defining conditions. There is currently no cure for AIDS or vaccines to prevent this disease. The treatment protocols, generally considered to be most effective, typically involve two or three different anti-retroviral drugs used in combination. The use of antiretroviral drugs has reduced the morbidity and mortality associated with AIDS, however, a significant number of HIV infections have become resistant to antiretroviral treatment. The use of alternative treatment approaches has been a widespread practice since the existence of HIV/AIDS was first reported by the Centers for Disease Control of Atlanta. The cost and the politics of access to antiretroviral therapies, appears to have encouraged the use of other treatment approaches. Stigma associated with HIV/AIDS and denial is factors which have obstructed testing for HIV and the use of antiretroviral drugs. The effectiveness of alternative therapies has not been established, despite widespread use by people living with HIV/AIDS. There is no cure or any vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and have side effects. The following are the different classes of medications used in treatment of HIV/AIDS patients. •Reverse transcriptase inhibitors: These drugs inhibit the ability of the virus to make copies of itself. The following are two classes of these inhibitors: 1) Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). 2) Non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs are commonly used in combination with NRTIs to help keep the virus from multiplying. •Protease inhibitors (PIs): These medications interrupt virus replication at a later stage in its life cycle, preventing cells from producing new viruses. The common side effects of these drugs are; fatigue, anemia, diarrhea, nausea or vomiting, dizziness or headaches, insomnia, pain and nerve problems, skin rash, injection site reactions, dry mouth, weight loss and vivid dreams. In this study the efficacy and safety of Faramir to treat HIV+ patients were investigated. Faramir with the code number of IRC201112124076N6 (Iranian registry of clinical trials) was registered in December 18th, 2012. This drug, made of natural elements under a complex process, was orally administered in seven HIV+ patients. The effect of Faramir on viral load showed a decrease number of HIV viruses in the bodies of 6 patients (Fig.1). One patient (patient number 7) took only one viral load test at the beginning of the study. The results after 3 months of therapy showed that even though 4 patients withdrew from the drug, the viral loads were reduced in their bodies. The viral load became undetectable in 3 patients with substantial improvement in their clinical conditions (Fig.1, patients' codes 2, 4, 6). This drug has no direct effect on immune system in short term and the CD4 count showed fluctuation within 6 months of therapy. However, by decreasing the number of virus in the body, the immune system naturally improves after 12 months of therapy (Fig.2). For example, the patient's code number 2 voluntarily continued his medication for 12 months and CD4 count was significantly increased from 603cells/mm3 to 1310cells/mm3. Three patients ( codes 1, 3 and 4), after nine months of treatment under Faramir administration, changed their drug regimens to HAART or IMOD showed +266 cells/mm3, +76 cells/mm3, -18 cells/mm3 in CD4 count changes. This means that the maximum increase of +266 was observed in CD4 count. In the present study, in comparison, showed significant increase in CD4 count was observed; i.e., in the patient code number 2, (+707cells/mm3). In contrast with other HIV drugs, Faramir had the least side effects in the period of experiment which were managed easily. In the toxicity tests performed on the three groups of male rats, oral administration of Faramir showed no poisonous effect or mortality after 72 hrs. (Table 1). No clinical side effects were observed till the end of testing, meaning that Faramir can be classified in the non-poisonous medication category. Conclusion: Faramir, as a natural drug with minimal side effects can be a promising agent to treat patients with HIV/AIDS. Short-term use of this drug effectively eliminates the virus and in long term, may increase CD4 count. Further study is required to investigate the long term CD4 count, the mode of action, efficacy and safety of this drug. Competing interests The authors declare that they have no competing interests. Acknowledgements This research was supported by Iranian research center for HIV/AIDS(IRCHA), Tehran University of Medical Sciences, Iran. 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