HIV Antiviral Properties Of Ivermectin: An Off-Label Treatment
- MemberOctober 18, 2021 at 10:06 pm
HIV…Not talked about much since SARS-CoV-2. The dangerous drugs used in the first efforts to battle HIV is in a way like the dreaded entries into VAERS database by people suffering after mRNA vaccinations for SARS-CoV-2.
“The first generation of FDA-approved HCV drugs included interferon alfacon-1 (approval year: 1997, discontinued in 2013 due to severe adverse events), ribavirin (1998), pegylated interferon alfa-2b (2001), and pegylated interferon alfa-2a (2002) (20). Although these drugs had low cure rates, a treatment duration of 48 weeks, and may cause severe adverse events, they were the only standard-of-care treatments over a decade. Interferons and ribavirin were chosen because they exhibited a certain inhibitory capacity against other viral infections, and their low effectivity is largely due to their low specificity against HCV. Fortunately, the development of direct-acting antivirals (DAAs) targeting the two main HCV enzymes, NS3 protease and RdRp (20), has decreased treatment duration to 8 weeks and increased the cure rate to nearly 100%.” https://www.frontiersin.org/articles/10.3389/fimmu.2021.635371/full
More than a million Americans are living with HIV. HIV is a virus that attacks a person’s immune system—specifically CD4 cells. These cells are a type of white blood cell, which play an important role in fighting infections. HIV damages CD4 cells and reduce their numbers. This makes the body more prone to infections and other diseases, such as certain types of cancer. Left untreated, HIV can lead to AIDS and be fatal. Fortunately, HIV drug therapy can help people with HIV live active, healthy lives for much longer than in the past.
Classes of HIV Medications
Evidence shows early HIV treatment—regardless of CD4 count—leads to fewer complications and possibly even deaths. As a result, current expert guidelines recommend starting HAART (highly active antiretroviral therapy) for anyone with HIV. HAART with at least three drugs is standard care for HIV infection. There are several classes of HIV drugs doctors can use when designing HAART:
Nucleoside reverse transcriptase inhibitors (NRTIs). These drugs block reverse transcriptase, an enzyme the virus needs to make new viruses. NRTIs block new virus production by inserting themselves into the virus’s DNA as it tries to copy itself. NRTIs were the first class of HIV drugs. In general, an initial HAART regimen will include two of these drugs.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs). This class binds to reverse transcriptase and changes the enzyme in way that makes it unable to function. Doctors may use an NNRTI as the third drug in an initial HAART regimen.
Protease inhibitors (PIs). These drugs block protease, another enzyme the virus needs to reproduce. PIs can be part of an initial HAART regimen. However, they need the addition of a pharmacokinetic enhancer—a drug that boosts the effects of PIs on HIV.
Integrase strand transfer inhibitors (INSTIs). INSTIs—or simply integrase inhibitors—block HIV from making copies of itself. HIV inserts its DNA into the CD4 cell’s DNA in order to replicate. Integrase inhibitors block the HIV enzyme that allows the transfer. INSTIs can be the third drug in an initial HAART regimen.
Entry inhibitors. These drugs are also known as CCR5s (chemokine coreceptor antagonists). They block a protein—CCR5—on the surface of CD4 cells that the virus needs to get inside the cell. This prevents the virus from entering. Only certain strains of HIV use this protein. A blood test can tell your doctor if your HIV strand will respond to this class.
Fusion inhibitors. These drugs prevent HIV from merging with the cell membrane of CD4 cells. This prevents the virus from entering the cell. This class is not currently recommended as first-line treatment. Instead, it is an option for treatment-experienced patients needing to change regimens.
Pharmacokinetic enhancers. This class boosts the effectiveness of other drugs. They accomplish this by interfering with the breakdown of the other drug. This increases the blood levels of the drug.
Common HIV Medications
Your doctor will consider your other health conditions, ease of taking the regimen of HIV drugs, and drug side effects and interactions when deciding on the best treatment for you. It is possible to transmit a drug-resistant virus. Your doctor will find out whether you have a wild-type virus (naturally occurring virus) or a drug-resistant one (mutated virus).
Here are 10 commonly prescribed HIV drugs:
1. Atripla (efavirenz + tenofovir + emtricitabine) combines an NNRTI and two NRTIs into one medication. The usual dose is once daily on an empty stomach—one hour before or two hours after a meal. Dizziness, diarrhea and tiredness are common side effects. Serious, life-threatening side effects are also possible, such as liver problems and a buildup of lactic acid in the blood.
2. Complera (rilpivirine + tenofovir + emtricitabine) combines an NNRTI and two NRTIs. The usual dose is once daily with a meal. Strange dreams, trouble sleeping, depressed mood, headache, and digestive problems are common. Serious liver problems and lactic acid buildup in the blood can occur.
3. Genvoya, Stribild (elvitegravir + cobicistat + tenofovir + emtricitabine) combines an INSTI, a pharmacokinetic booster, and two NRTIs. You usually take it once a day with food. Headache, nausea, and diarrhea are common side effects. Like Atripla and Complera, serious liver problems and lactic acid buildup in the blood are possible.
4. Isentress (raltegravir) is an INSTI you usually take twice a day. Nausea, headache, dizziness and fatigue are common side effects. Although rare, muscle breakdown leading to kidney failure may occur.
5. Norvir (ritonavir) is a PI you usually take twice daily with meals. Digestive side effects are common, as are headache and burning or tingling sensations. Norvir can also cause serious side effects and drug interactions. Tell your doctor and your pharmacist about all of your medications.
6. Prezista (darunavir) is a PI you usually take with ritonavir either once or twice a day. Ritonavir acts as a pharmacokinetic booster. Digestive problems, headache, and changes in body fat are common side effects. Severe skin reactions and liver problems are also possible.
7. Tivicay (dolutegravir) is an INSTI you take once or twice a day. Headache, fatigue, sleep problems, and changes in body fat are common side effects. Serious liver problems are also possible.
8. Triumeq (dolutegravir + abacavir + lamivudine) combines an INSTI and two NRTIs. The usual dose is once daily. Headache, fatigue, sleep problems, and changes in body fat are common side effects. It is also possible to have serious side effects, including a serious allergic reaction, liver problems, and a buildup of lactic acid in the blood.
9. Truvada (emtricitabine + tenofovir) combines two NRTIs. The usual dose is once daily. Abnormal dreams, trouble sleeping, depressed mood, headache, and dizziness are common side effects. Like other NRTI combinations, liver problems and lactic acidosis buildup in the blood is also possible.
10. Vemlidy, Viread (tenofovir) is an NRTI you usually take once a day. Digestive problems, fatigue, headache, depressed mood, sleep problems, and changes in body fat are common side effects. Like other NRTIs, serious side effects are possible, including liver problems and lactic acid buildup in the blood.
Ivermectin can e used to combat both HIV and SARS-CoV-2. Here is an excerpt from “Drug repurposing for the treatment of COVID-19: Pharmacological aspects and synthetic approaches”
“Ivermectin has been shown to have in vitro antiviral activity against a broad range of viruses, such as human immunodeficiency virus (HIV-1), dengue fever, influenza, Zika and Ebola viruses . As an anti-HIV agent, it acts by inhibiting the interaction between the HIV-integrase protein (IN) and the importin (IMP) α/ß1 heterodimer, which is responsible for IN nuclear import of integrase protein. However, this compound was also able to inhibit nuclear import of viral proteins, e.g. simian virus SV40 large tumor antigen and dengue virus (DENV) non-structural protein 5 , . Still, it has been shown that it is active against RNA viruses such as DENV 1–4, West Nile Virus, and influenza , , . Its wide activity is attributed to the fact that many RNA viruses rely by on IMPα/β1 during infection. Considering that SARS-CoV-1 proteins are important for IMPα/β1 during infection, it was inferred that ivermectińs nuclear transport inhibitory activity could also work well against SARS-CoV-2. At 24 h, there was a 93% reduction in viral RNA present in the supernatant (indicative of released virions) of samples treated with ivermectin compared to the vehicle DMSO. Indeed, in vitro studies conducted with Vero/hSLAM showed that 24 h after the addition of ivermectin, a 93% reduction in viral RNA was observed, and no more viral material was present in the medium after 72 h .”
History of Ivermectin, From The Knowledge Available Six Years ago:2015
Human Side of Ivermectin: Merck’s Roy Vagelos Pledges to Do the Right Thing.
In addition, ivermectin had great potential for human helminthic infection. After Campbell’s group found ivermectin had great activity against Onchocerca infection in horses, he hypothesized the compound could also be useful in treating river blindness in humans, caused by Onchocerca volvulus. Onchocerciasis, or river blindness, is the second most common cause of blindness, after trachoma. It also causes a debilitating, chronic skin disease due to inflammation caused by microfilaria released from adult worms. Mohammed Aziz of Merck led the clinical trials that confirmed Campbell’s hypothesis that ivermectin would be effective for onchocerciasis, and remarkably so. A single dose of ivermectin led to a dramatic reduction in microfilaria burden in humans, with amelioration of disease. One drawback was that ivermectin did not kill adult worms, which would resume microfilaria production after about six months; thus, about six to eight repeated doses at six-month intervals are necessary. Nonetheless, no drug came close to ivermectin’s safety and efficacy for river blindness. In October of 1987, Roy Vagelos, Merck’s Chief Executive Office, made the unprecedented decision to donate as much Mectizan, alias ivermectin, as was needed, for as long as it was needed, to anyone who needs it. Merck still stands behind this decision today, providing ∼300 million doses annually of ivermectin for the control and eventual eradication of river blindness and, more recently, for lymphatic filariasis (elephantiasis), another human helminthic disease that ivermectin treats effectively.
Ivermectin and Elimination Campaigns.
The deployment of ivermectin, coordinated by the Carter Center and Pan American Health Organization, has led to river blindness being eliminated from three of six countries in the Americas as certified by the WHO, whereas transmission was halted in a fourth. Today transmission has been restricted to the Amazonas region of Brazil and to Venezuela.* In Africa, where the disease was much more prevalent, rates of infection are down fivefold, and in 2014, most African countries with endemic infection decided to move from river blindness control with annual doses of ivermectin to elimination campaigns with twice-annual dosing (3). Moreover ivermectin has recently been used in elimination campaigns for lymphatic filariasis, greatly reducing the numbers of human cases as well (4).
Fortunately, human helminthic resistance to ivermectin has not (yet) emerged despite the large-scale campaigns undertaken, and it remains effective for river blindness and lymphatic filariasis. However, ivermectin resistance has emerged in some animal helminths, prompting agencies such as the Bill & Melinda Gates Foundation, Drugs for Neglected Diseases Initiative, and partners to seek new drugs for river blindness actively. In addition, a drug that kills adults (macrofilaricidal) is actively sought because it would simplify elimination campaigns, which now require twice-annual mass administration of ivermectin for at least several years to eliminate infection and transmission.
Natural product-derived antiviral therapy for HIV virus: Ivermectin (Brand name: Heartguard/Mectizan/Stromectol) increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production via up regulation of its target gene, 25/August/2017, 11.46 pm
Natural product-derived antiviral therapy for HIV virus: Ivermectin (Brand name: Heartguard/Mectizen/Stromectol) increases Heme oxygenase 2 (HO-2) expression, blocks N-myristoylation of HIV-1 Gag protein, disrupts HIV-1 budding, and restricts HIV-1 production via up regulation of its target gene, 25/August/2017, 11.46 pm
Natural Products and HIV/AIDS
Daniele C. Cary
and B. Matija Peterlin
Published Online:1 Jan 2018https://doi.org/10.1089/aid.2017.0232
The Treatment of Scabies With Ivermectin
Onchocerciasis and human immunodeficiency virus in Western Uganda: Prevalences and treatment with ivermectin
Ivermectin alone or in combination with benzyl benzoate in the treatment of human immunodeficiency virus-associated scabies
May you be free of HIV/AIDS