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Thursday, September 23, 2010

8.19 Stop HIV/AIDS

Physician's Notebooks 8 - http://physiciansnotebook.blogspot.com - See Homepage


19. HIV-AIDS - Update 12 March 2018
Infectious AIDS (acquired immunodeficiency syndrome) was first reported in 1981. AIDS is due to HIV (Human immunodeficiency viruses, HIV-1 and HIV-2).
   HIV was infecting humans as early as 1959, Why was it not noticed before 1981 and why did it suddenly rise to be world epidemic since? It may be explained by the more careless sexual promiscuity and increased men sexing men during the 1960s and 70s; also the recent higher human mobility that spreads infection, and mutation of the original HIV strain toward higher infectiousness and virulence.
   
The big risk factor is promiscuity – the more partners the more risk. Another risk factor is bare-penis sex. Consistently using condom prevents infection from coitus. Receiving injections and blood transfusions is another risk. Highest risk is intravenous drug-shooter who shares needle and syringe and uses no sterile precaution.
   The risk of HIV from blood transfusions and blood products is from whole blood and packed cells, and from transfusions of platelets, white blood cells and blood plasma. The other blood products - hyperimmune globulins against hepatitis and other virus infections, hepatitis vaccines and RH immune globulin given to pregnant women after birth or abortion - have no risk of HIV unless non sterile injection technique or equipment is used. All organ or cell transplants carry a risk of HIV.
   In the U.S. the risk of HIV from a blood transfusion in 2013 was 1 HIV infection in 1.5 million units of blood. It works out to eleven HIV infectious blood donations each year. (But in Africa or other 3rd world countries the risk is much higher) 
   Looking at the general risk factors for HIV/AIDS,  male homosexual sex acts are the highest risk for HIV; 79% of HIV infections acquired in USA during 2009 were from male-to-male homosexual contacts.

At the center of a Human Immunodeficiency Virus is its controlling corkscrew RNA (Ribose nucleic acid, single stranded copy of one of its two DNA strands). Reverse transcriptase is the key enzyme in viral replication during infection; it catalyzes RNA conversion to DNA, which allows an infecting virus particle to insert into human DNA in chromosome and take control to make an infected cell a factory for producing virus bodies. The structural protein p24 forms the virus oval around the RNA strands.
   Detection of this protein is an early test for HIV, even before the HIV antibody blood test turns positive. The virus’s outer body (envelope) is important in initiating viral infection of a human cell and also in antibody immune response to HIV. Studding this outer viral envelope membrane are the spike-like envelope glycoproteins, gp120 and gp41. The gp120 fits like a key in keyhole of CD4 human lymphocyte receptor pit on surface of the CD4 lymphocyte and helps the fusion of the virus to the cell and injection of the HIV RNA into the cell.
   How does an HIV infection start? First, the body fluid of the infectious person loaded with HIV gets past outer defense (skin and mucus membrane of body cavity such as vagina, rectum or mouth) of a person to be infected. This can occur sexually (in order of risk from high to low: penis-rectum, penis-vagina, rectum-penis, vagina-penis, penis-mouth, mouth-penis, mouth-mouth) or by injection (IV injection with syringe & needle sharing, contaminated needle or finger stick, HIV infected blood in transfusion or blood products) or from mother to fetus and newborn via placenta, birth canal or breast feeding; or, in addition, by medical contact (Dentist or surgeon to patient, or patient to surgeon or transplants including cells only as in cornea). The HIV from infected person gets liberated into the body of a previously uninfected person and the virus particle enters the person's blood. 
   The number of virus particles that enter the system at the infectious instant is important in infection and prevention. A small HIV load (less than 100 particles) has high probability of being killed off by your natural killer cells that patrol blood as first line of defense against new virus infection. Attempt at chemo-prevention will have more chance of success, the lower the infectious viral load. The practical import of this is that a protective measure not always effective may work with a low viral load. But don’t depend on it.

HIV infection of CD4 lymphocyte: HIV gets into body and first there is free HIV in blood plasma. For AIDS to develop, the HIV must invade your CD4 lymphocyte. Only a small percentage of lymphos have the CD4 surface receptor and when an HIV encounters a CD4 lympho it attaches to it by insertion of its external envelope spike GP120 into the CD4 pit like key-in-lock slot. This locks the HIV onto the surface of the CD4 cell (fusion) and then the individual HIV explodes, shooting its capsid (HIV nucleus with RNA strand) into CD4 cell interior. The HIV capsid, which contains RNA strand and p24 protein container, gets into cell nucleus and the HIV-RNA strand catalyzed by DNA polymerase contained in the capsid splits and with assistance of reverse transciptase converts to double-stranded DNA, and the viral DNA inserts itself into a human cell chromosome and takes control of the cell reproductive process. It may take the cell down one of two alternative pathways depending on conditions. 
   Mostly it turns infected cells into a factory to produce many thousand HIV and the cells burst (lysis) and liberate more HIV into blood. Then the offspring HIV infect more CD4 cells.
   Much less commonly, in some HIV-infected CD4, the HIV DNA remains inactive. It is important to understand that in these dormant HIV-infected cells, the HIV can no longer be identified by its typical characteristics. Only the fact that one chromosome in the CD4 cell nucleus contains a sequence of HIV DNA might tell it on an electron microscope level. In that case, the only way to demonstrate HIV infection is to shock the infected cell out of dormancy and stimulate the HIV genome (DNA functioning as gene in the cell chromosome) to enter its lytic phase and turn the dormant infected cell into a factory to produce thousands of HIV. In the dormant state, there is no way an anti-HIV drug can get at the dormant infected cells; also they are unrecognizable to anti-HIV antibodies from a vaccine. Because of these cells, the chemotherapeutic cure of HIV-infection and a successful vaccine therapy of already existing infection remain elusive.
   
The signs and symptoms of AIDS, excepting dementia, are all explained as being caused by a destructive effect of HIV infection of CD4 lymphocytes and a loss of immune function that follows quantitative depletion of the CD4 lymphocytes. The CD4 lympho is the helper-inducer subset of lymphocytes with many immune functions. There are 2 types of CD4-related immune dysfunction: one qualitative, meaning total cell function is compromised immediately on becoming infected; and the other quantitative, which is the effect of progressive destruction of the CD4 lymphos, leaving less and less CD4 lymphos per unit volume of blood. The qualitative effect is minor but the quantitative effect gives the symptoms of AIDS based on level of CD4 lympho below normal. The normal CD4 count is c.1000 or more per microLiter whole blood. This count starts dropping 6 months or more after infection on a smooth downward slope over several years. As the drop gets greater, normal bacteria (E.coli in intestine), yeast microbes (Candida in mouth), and some dormant viruses (chickenpox-zoster in spinal ganglia) that are normally prevented from infecting the body by a person's natural  immunity escape control and cause opportunistic infection (Diarrhea from E. coli, beefy red tongue and vaginitis from yeast, herpes zoster shingles from re-activated chickenpox virus).
   Clinical diagnoses of AIDS are being made when CD4 cell counts drop below 500/microLiter blood serum. The typical AIDS wasting away begins to afflict patient when CD4 lympho count falls below 200, and death comes when CD4 falls below 50.
   It has been estimated between 26% and 36% HIV-infected persons develop AIDS within 7 yrs of start of HIV infection, and an additional 40% develop lesser signs of immune dysfunction during this time. This suggests that HIV cell infection in the body is controlled partially by the immune response. Eventually a large percent of HIV infected persons die of AIDS but today with good anti-retroviral therapy, many are surviving past 25 years.
   Initial infection with HIV gives flu-like fever with sore throat and faint flat red rash on upper torso with small ulcers in mouth.(Easily overlooked) During this acute initial phase of infection, HIV level in blood is 107, or 10-million virus particles per milliliter (ml), and with it a high level of p24 virus protein, only part of which is connected to virus-infected cells. Much of the p24 is free in the blood plasma and it coats the surface of uninfected CD4 lymphos making them targets for destruction by immune killer cell. (Innocent bystander effect)
   Studies show a clinically important period up to 3 weeks after HIV contact during which HIV infected patient may give false negative HIV test even as his blood contains high concentration of HIV particles and therefore is highly infectious. Such a person might test negative on the HIV screening test for blood donation and donate blood that will cause AIDS in recipients or donate sperm to an artificial insemination that will cause AIDS in recipient or donate an infected organ or cells of cornea in eye. And such an HIV-negative person may have what he considers safe sex because of a yesterday’s HIV negative test report yet still infect his partner who will eventually die of AIDS.

HIV In India: Infected Blood Transfusions Caused 2,234 Cases In 17 Months

   The course of AIDS parallels the line of dropping CD4 lympho count. At start, HIV grows unopposed and virus count of 107/ml plasma is found by 6th week as well as similar high concentration of p24 antigen. By end of the first month after start of infection one sees start of rise of antibodies to p24 and antibodies to gp120, and a partially effective protective immune response that targets the infected CD4 cell and gives positive HIV test. At this point, several months into the infection with partial immune protective response, the HIV concentration in blood drops to 104 – 105 (10,000 to 100,000 per ml blood plasma). The acute symptoms clear up and are followed by a stable no-symptom period of several months to years. But all this time the CD4 lympho count is gradually falling and when it falls below 500 to 200/microliter the typical AIDS develops (weight loss, diarrhea, opportunistic infection, Kaposi sarcoma) gradually worsening until, in absence of treatment, death comes from pneumonia, overwhelming bacterial infection, dementia, or the sarcoma.

The need for intelligent sex that avoids mindless promiscuity remains the key to not becoming infected with HIV. The problem has been increased by propaganda in favor of having sex with strangers that takes the form of an incorrect idea that life without sex is unhealthy and unhappy.

Start with a critical attitude toward potential partner – when it comes to having sex, you’re on your own; believe no one and no thing (Especially latest received opinion by politically correct but factually incorrect pro homo activists) but documented fact and correct knowledge. Every sexual act that involves the potential exchange of body fluid between partners – from open-mouth kissing (Most people are taught kissing is safe from HIV/AIDS; this is not an absolute because body fluids are being exchanged; and even 1 case out of a thousand means an entry into Hell) should be preceded by practical proof of no HIV infection. Practical proof’ means two negative HIV antibody tests 3 weeks apart, the last one reported within the week on paper with the potential partner name and testing institution and date.
   And do not merely rely on HIV test, important as it is. Avoid sex with person who is high risk for HIV because of uncontrollable pattern of sexuality such as male homosexual or bisexual man who follows the “gay” lifestyle or an IV drug user, or a person you know by reputation to be hypersexual (so called nympho, satyr, womanizer, tramp). As a fallback line of defense, use condom with good knowledge, every time you fall off your wagon and you have coitus or rectal sex with someone whose HIV blood test status is unknown or otherwise suspect.
   This all assumes that the ‘You’ I address here is keeping an accurate finger on the pulse of your own HIV status by blood testing if even the slightest risk of HIV appears. Keep in mind that a negative HIV blood test can only ascertain absence of HIV infection up to 3 weeks before the blood was drawn. So if you have a single potential HIV contact and you get an HIV blood test that is negative right after, then you must wait more than 3 weeks and get another test negative before you can breathe sigh of relief.
   Two tests – p24 antigen and HIV particle test can determine HIV infection by 1 to 2 weeks but they are not routinely obtained. Nevertheless a sufficiently aggressive person could seek out and get such tests.
   Chemoprevention of HIV infection after first contact is now routinely recommended for the healthcare worker who experiences exposure to HIV body fluid (most commonly contaminated needle stick of finger when trying to re-sheath a needle after giving injection but also splash into eyes, nostrils, mouth or open wound area). This chemoprevention could also be visualized after inadvertent accidental injection of blood or its product, or after single sexual encounter of HIV negative person with person whose HIV positive status is not ruled out by recent test and/or history. Recommendation for routine use of chemoprevention after acute exposure to HIV infection is based on increasing evidence of its protective effect in experiment where animal is injected with HIV and treated with chemo-preventive drug and also from prospective human study of health worker who sticks finger on HIV contaminated needle (0.3% risk of HIV infection). High dose must be started ASAP (within 4 hrs best) after exposure to HIV. The US PHS has established a hotline for immediate post exposure prophylaxis: Tel: 1 888-448-4911 (May be accessed from anywhere on Earth and a physician expert will speak with you) and also on the Internet at http://pepline.ucsf.edu.pepline or www.nccc.ucsf.edu.

Treatment of HIV infection and AIDS: Much progress has been made since 1981 to 1984, when there was no treatment. The treatment now is witness to more than 20 effective licensed (in US) drugs that, used in groups of 3 or 4 by expert, can bring a patient with AIDS back to a symptom-less status with good life quality for years. What is not yet achieved is cure in the sense that medication can be stopped without risk of AIDS after (Rare cases are reported but as yet single digit).
   The principle that guides the expert in treatment of HIV infection is the HIV high mutation rate causing single drug treatment to fail due to drug resistance within several months. Thus the reason for combined drug treatment! The anti-HIV drugs are of four classes based on the enzyme they block or inhibit in the HIV infective cycle. The classes are: nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), protease integrase inhibitors (PI or II), and the viral fusion inhibitors (FI). First is to combined drugs, one of each type drug. Next is to use a test to determine success of treatment, and also to help decide when to start treatment. The accurate test for HIV numbers in blood has shown that during much of the no-symptom period of HIV infection, the high virus count is destroying the CD4 lympho helper-inducer cells and worsening outcome. So treatment is based on frequent HIV and CD4 lympho count in blood started ASAP after detecting HIV infection and continued with aim of keeping HIV count at zero (undetected by present method). Failure of particular drug therapy can be diagnosed early by rising HIV in blood. The CD-4 lympho counts, which used to require a drop below 200 per microliter whole blood before starting treatment, have now been up-ticked by many experts to 500 and much evidence is accumulating that ASAP after HIV positive conversion is the time to start drug treatment, which continues for life as long as HIV is low or zero and not rising. If that is detected, a new set of drugs replaces the old. It is hoped that in some cases longer than 10-year treatment with zero HIV will result in loss of dormant infected HIV cells in the body and cure. Success in treatment requires going to world-class AIDS center. Treatment is expensive and side effects occur but if there is a need to live a useful life and if the AIDS patient follows the wise expert advice, he or she can succeed. One needs to combine drug treatment with living the healthiest lifestyle possible. And one should give up the usual free sex relationship because of the risk of passing HIV to HIV-negative person. Sex between HIV+ persons also poses a risk of passing high drug resistant strain from one HIV+ to another and ruining a successful drug treatment.

Endnotes; Beware of health food store supplements like Zn (zinc compounds) or mega vitamins or herbals that are highly touted against AIDS. They have been tested and found ineffective. They waste time, money and hope. 
   Breast feeding ought to be a No-No if the new mother is HIV+ or her HIV status is not known. HIV/AIDS is passed in mother's milk and infection rates of breast fed babies up to 30% have been documented in Africa.

Latest on Preventive Vaccine against AIDS: A cellular vaccine has completed testing in Thailand and shows a 30 to 40% potential protection against acquiring HIV infection. This is still not enough to advise the vaccine for general use but is a real breakthrough in that it is the first partial success after 20 years of testing.
   Build on what is here now by doing seminars.
 END OF CHAPTER. To read on next now, click 8.19a Advice to Female Sex Workers














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