Human immunodeficiency virus (Hiv), the retrovirus responsible for acquired immune scantness syndrome (Aids) has been around since in the middle of 1884 and 1924 (while lentiviruses, the genus to which Hiv belongs, have existed for over 14 million years) when it entered the human people from a chimpanzee in southeastern Cameroon during a period of rapid urbanization. At the time, no one noticed nor knew that it would effect in one of the deadliest pandemics. Nor was whatever aware that some would possess a natural immunity, a cure would remain elusive a decade into the 21st century, and a vital estimate of deceased victims would be purged from mortality statistics distorting the pandemic's severity.
As the estimate of cases spread from Cameroon to neighboring countries, namely the Democratic Republic of Congo (Drc), Gabon, Equatorial Guinea, and the Central African Republic, they drew little concentration even as victims died in scattered numbers from a series of complications (e.g. Pneumocystis pneumonia (Pcp), Kaposi's sarcoma, etc.) later attributed to Aids. This was likely because of Africa's little interaction with the developed world until the uncut use of air travel, the isolated, low incidence of cases, Hiv's long incubation period (up to 10 years) before the onset of Aids, and the absence of technology, reliable testing methods and knowledge surrounding the virus. The earliest confirmed case based on Zr59, a blood sample taken from a patient in Kinshasha, Drc dates back to 1959.
Hiv Antiretroviral Drugs
The outbreak of Aids finally gained concentration on June 5, 1981 after the U.S. Centers for Disease control (Cdc) detected a heap of deaths from Pcp in Los Angeles and New York City. By August 1982, as the incidence of cases spread, the Cdc referred to the outbreak as Aids. The responsible retrovirus, Hiv, was isolated nearly a year later (May 1983) by researchers from the Pasteur organize in France and given its lawful name in May 1986 by the International Committee on Taxonomy of Viruses. during this period, Hiv-related mortality rates rose steadily in the United States peaking in 1994-1995.
Hiv:
Hiv is round in shape and almost 120 nanometers (nm) in diameter (or 60 times smaller than a red blood cell). It is composed of two copies of single-stranded convoluted Rna surrounded by a conical capsid and lipid membrane that prevents antibodies from binding to it. Hiv also consists of glycoprotein (gp120 and gp41) spikes and is a extremely mutating virus. Its genome changes by as much as 1% each year, significantly faster than "killer" cytotoxic T-Cells (Cd8+) can adapt. It is transmitted through physical fluids.
Per Cd4 Cell Tests (Fact Sheet estimate 124, Aids InfoNet, 21 March 2009), when "Hiv infects humans" it infects "helper" T-4 (Cd4) cells that are vital in resisting infections. Hiv does so by merging its genetic code with that of T-4 (Cd4) cells. Hiv's spikes stick to the surface of T-4 (Cd4) cells enabling its viral envelope to fuse with their membrane. Once fused, Hiv pastes its contents into the Dna of T-4 (Cd4) cells with the enzyme, integrase, so that each time T-4 (Cd4) cells replicate, they yield supplementary "copies of Hiv," reducing the count of wholesome T-4 (Cd4) cells. Then as wholesome T-4 (Cd4) cells, which come in millions of families geared towards definite pathogens are eliminated, the body is rendered defenseless against the pathogens "they were designed" to fight until ultimately, the immune principles is overwhelmed.
When the T-4 (Cd4) cell count drops below 200 cells per cubic mm of blood (or a division of? 14% of total lymphocytes; normal counts range from 500-1600 or 30%-60% of lymphocytes), indicative of serious immune principles damage, the victim is deemed to have Aids ("the end point of an infection that is continuous, progressive and pathogenic per Richard Hunt, Md (Human Immunodeficiency Virus And Aids Statistics, Virology - lesson 7, Microbiology and Immunology On-line (University of South Carolina School of Medicine, 23 February 2010)) and is vulnerable to a multitude of opportunistic infections. Examples are Pcp, a fungal infection that is a major killer of Hiv-positive persons, Kaposi's sarcoma, a rare form of cancer, toxoplasmosis, a parasitic infection that attacks the brain and other parts of the body and cryptococcosis, a fungal infection that attacks the brain and spinal cord (both regularly occur when the T-4 (Cd4) cell count drops below 100), and mycobacterium avium complicated (Mac), a bacterial infection that can be localized to a definite organ (usually the bone marrow, intestines, liver, or lungs) or widespread, in which case it is referred to as disseminated mycobacterium avium complicated (Dmac) (which often occurs when the T-4 (Cd4) cell count drops below 50).
Natural Immunity:
Since the onset of the Hiv/Aids pandemic in 1981 cases of people with a natural immunity to Hiv have been documented. Although these persons, called long-term non-progressors (Ltnps) are infected with Hiv, they never organize Aids. When Ltnps are infected, some suffer an preliminary drop in their T-4 (Cd4) cell count. However, when their T-4 (Cd4) cell count reaches around 500 it stabilizes and never drops again preventing the onset of Aids. Furthermore, while Cd8+ T-Cells (even in large numbers) are ineffective against Hiv-infected T-4 (Cd4) cells in progressors (persons without a natural immunity to Hiv), the National Institutes of health (Nih) reported in a December 4, 2008 press issue that "Cd8+ T-Cells taken from Ltnps [can efficiently] kill Hiv-infected cells in less than [an] hour" in which "a protein, perforin (produced only in negligible amounts in progressors), artificial by their Cd8+ T-Cells punches holes in the infected cells" enabling a second protein, "granzyme B" to drill and kill them.
Per Genetic Hiv Resistance Deciphered (Med-Tech, 7 January 2005) the roots of this immunity dates back a thousand years due to "a pair of mutated genes - one in each chromosome - that preclude their immune cells from developing [Chemokine (C-C motif) receptor 5 (Ccr5) receptors] that let [Hiv penetrate]." This mutation likely evolved to furnish added protection against smallpox according to Alison Galvani, professor of epidemiology at Yale University. Based on the newest scientific evidence, the mutated Ccr5 gene (also called delta 32 because of the absence or deletion of 32 amino acids from its cytokine receptor) located in Th2 cells, developed in Scandinavia and progressed southward to central Asia as the Vikings vast their influence. Consequently up to 1% of Northern Europeans (with Swedes being in the majority) followed by a similar division of Central Asians have this mutation, which if inherited from both parents provides them total immunity while someone else 10-15% of Northern Europeans and Central Asians having inherited the mutation from one parent exhibit greater resistance in lieu of perfect immunity to Hiv.
At the same time, even though the Ccr5 mutation is absent in Africans, a small also exhibit division natural immunity (possibly developed through exposure) to Hiv/Aids - Cd8+ T-Cell generation that effectively kills Hiv-infected cells and mutated human leukocyte group A (Hla) antigens that coat the surface of their T-4 (Cd4) cells to preclude Hiv from penetrating based on an laberious study of 25 Nairobi prostitutes who per The astounding Cases of people with Natural Immunity against Hiv (Softpedia, 27 June 2007) have "had sex with hundreds, possibly thousands of Hiv-positive clients" and shown no sign of contracting Hiv.
In addition, people with larger numbers of the Ccl3L1 gene that produces cytokines (proteins that "gum" up Ccr5 receptors) to preclude Hiv from entering their T-4 (Cd4) cells, per Genetic Hiv Resistance Deciphered have greater resistance to Hiv in comparison to others within their ethnic group that possess lesser quantities of the Ccl3L1 gene and get "sick as much as 2.6 times faster."
At the same time, up to 75% of newborn babies also possess natural immunity (for reasons still not known) when exposed to Hiv-positive blood. Although born with Hiv antibodies - thus Hiv-positive, newborns "usually lose Hiv antibodies acquired from their Hiv-positive mothers within 12-16 - maximum 18 months," in which their "spontaneous loss of [Hiv] antibodies" without healing intervention is called seroreversion. "However, with the irregularity of very few instances, these infants are not Hiv-infected" conclusive proof of a natural immunity to Hiv.[1] Furthermore, when pregnant Hiv-positive women are administered extremely active antiretroviral therapy (Haart), which lowers the viral concentration of Hiv in their blood, an astounding 97% of their newborns lose their Hiv antibodies through seroreversion to become Hiv-free per the Eunice Kennedy Shriver National organize of Child health and Human development (Nichd) as posted under surveillance Monitoring for Art Toxicities Study in Hiv-Uninfected Children Born to Hiv-Infected Mothers (Smartt) (Clinical Trials.gov, 29 March 2008). However, at this time, it is not known if these newborns hold their natural immunity throughout their lives.
Eradication:
With a cure possibly unattainable, eradication of Hiv/Aids in the same way as smallpox (with no cure) was eliminated, may be the most feasible option. according to Dr. Brian Williams of the South African Centre for Epidemiological Modelling and Analysis, eradication of Hiv/Aids is an achievable goal that could be attained by 2050 if the current Hiv/Aids research paradigm is changed from focus on looking a cure to stopping transmission.
Per Dr. Williams such an effort would want testing billions of people annually. Though costly, the benefits would exceed the costs "from day one" according to the South African epidemiologist. whatever found with Hiv antibodies would immediately be administered antiretroviral therapy (which reduces Hiv concentration 10,000-fold and infectiousness 25-fold) to halt transmission, effectively ending such transmission by 2015 and eliminating the disease by 2050 as most carriers die out, according to his estimate. The presuppose for this optimism, per Steve Connor, Aids: is the end in sight? (The Independent, 22 February 2010), is a "study published in 2008 [that] showed it is theoretically potential to cut new Hiv cases by 95%, from a prevalence of 20 per 1,000 to 1 per 1,000, within 10 years of implementing a programme [sic] of universal testing and prescription of [Ha]Art drugs."
Even though clinical trials to test Dr. Williams' vision will start in 2010 in Somkhele, South Africa, way to Haart still needs to be improved greatly to purge the disease. Presently only about 42% of Hiv-positive people have way to Haart.
Furthermore, for eradication efforts to succeed, arresting programs (which currently reach fewer than 1 in 5 in sub-Saharan Africa, the epicenter of the pandemic where the average life-expectancy has fallen below 40 leaving about 15 million children orphaned) will have to continue to play an vital role in stopping transmission. Such programs though not little to, must contain abstinence, condom distribution, schooling re: transmission, safe sex, etc., and needle distribution to drug users (the latter which is badly lacking according to Kate Kelland, Failure to aid drug users drives Hiv spread: study (Reuters, 1 March 2010) with "more than 90% of the world's 16 million injecting drug users offered no help to avoid contracting Aids" despite the fact that such users often share needles and almost 18.75% are believed to be Hiv-positive).
Proof that such efforts can work is evident when the President's emergency Plan for Aids Relief (Pepfar) created in 2003 for Africa that provides funding focused on Haart and palliative care for Hiv/Aids patients, Hiv/Aids awareness schooling and arresting programs (condoms, needle-exchanges, and abstinence) and financial aid to care for the pandemic's orphans and other vulnerable children, is considered. Per Michael Smith, Pepfar Cut Aids Death Rate in African Nations (Med Page Today, 6 April 2009), the program "averted about 1.1 million deaths [from 2004-2007]... A 10% discount compared to neighboring African countries."
The "Disappearing" Victims:
Despite presuppose for optimism based on Dr. Williams' vision of eradication, the "disappearance" of Hiv/Aids victims is extremely disturbing. In fact, when current statistics are compared to past statistics, more than 19 million victims or triple the estimate of murdered Holocaust victims (1933-1945) have been purged from the lawful narrative (effectively minimizing the severity of the pandemic) without as much as a whimper of protest, possibly because demographically speaking, a statistically-significant estimate of the deceased fall into groups that have been and continue to be the subjects of racial, gender, cultural, and even religious discrimination. In the words of Charles King, an activist who spoke in San Francisco on World Aids Day in 2007, it is likely because Hiv/Aids has generally "taken the lives of people deemed expendable"[2] the same mentality used to illustrate Hitler's "Final Solution" and other pogroms.
Back on January 25, 2002 in Aids Death Toll 'Likely' to Surpass That of Bubonic Plague, scholar Says in British healing Journal extra Issue on Hiv/Aids (Kaiser Network), it was written, "Aids - which has already killed 25 million people worldwide - will overtake the bubonic plague as the 'world's worst pandemic' if the 40 million people currently infected with Hiv do not get way to life-prolonging drugs..."
A year earlier, Unaids listed the global death toll as 21.8 million with an increase of 3.2 million in 2002. By 2003, based on statistics reported by the World health organization (Who), Unaids, and U.S. Census Bureau as tabulated in The Global Hiv/Aids Epidemic: Current & hereafter Challenges by Jennifer Kates, M.A., M.P.A., Director Hiv Policy, Kaiser house Foundation the global death toll had risen to 28 million by February 2003. Add yearly mortality statistics of 3 million (2003), 3.1 million (2004 and 2005), 2.9 million (2006), 2.1 million (2007), and 2 million (2008, the most modern perfect year of reporting) per Unaids, and an estimated, conservative total of 1.4 million (if someone else 28% decline as occurred in the middle of 2006 and 2007 took place in the middle of 2008 and 2009) the global death toll for year-end 2009 would be almost 45.6 million. Yet, when Unaids released its newest narrative in November 2009 as reported in the Mail & Guardian (South Africa, 24 November 2009) the worldwide death toll through 2008 was listed as "passing 25 million," almost 19.2 million below the actual mark.
Per Aids cases drop due to revised data (Msnbc, 19 November 2007), the "disappearing" victims can be attributed to "a new methodology." While this may make sense with regard to prevalence since "[p]revious Aids numbers were largely based on the numbers of infected pregnant women at clinics, as well as projecting the Aids rates of confident high-risk groups like drug users to the entire people at risk" versus the new methodology that incorporates data from "national household surveys," it does not with regard to mortality figures which are calculated primarily from national Aids registries and/or death certificates based on the proximity of Hiv, T-4 (Cd4) cell counts below 200, and death caused by opportunistic Aids-related infections resulting from such low T-4 (Cd4) cell counts.
In retrospect, when viewing the approximate 45.6 million figure, few pandemics have killed more than Hiv/Aids - Smallpox (which had come in waves since 430 Bc until the World health organization (Who) certified its eradication in 1979), killed 300-500 million, Black Death/Bubonic Plague killed almost 75 million from 1340-1771, and Spanish Influenza killed in the middle of 40-50 million from 1918-1919.
Optimism for the Future:
Until Hiv/Aids can be certified as eradicated by the Who, despite the terrible economic toll it has taken, especially on sub-Saharan Africa (due to lost skills, shrinking workforces, rising healing costs) and other developing regions and its devastating toll in human lives and on families, there is presuppose for optimism.
As of December 2008, per Unaids, 33.4 million people are infected with Hiv, a 1.2% increase from a year earlier with much of the rise attributed to a declining mortality rate due to a 10-fold increase in availability of Haart since 2004. About 2.7 million persons were newly infected in 2008, 18% and 30% decreases in new Hiv infections globally since 2001 and 1996, respectively. In someone else promising sign, new Hiv infections in sub-Saharan Africa, responsible for about 70% of all Hiv/Aids-related deaths in 2008, has fallen by 15% since 2001. At the same time, there were almost 2 million Hiv/Aids-related deaths in 2008, a 35% discount from 2004 levels when the global mortality rate peaked.
Presently, the Hiv/Aids pandemic has begun to decline or stabilize in most parts of the world. Declines have been recorded in sub-Saharan Africa and Asia (although the mortality rate is addition in East Asia) while the pandemic has stabilized in the Caribbean, Latin America, North America and Western and Central Europe. The only part of the world where the Hiv/Aids pandemic is worsening is the Eastern European (especially in Ukraine and Russia) and Central Asian region.
The declines should continue as new methods of arresting and medicine are developed. Based on studies of Nltps, a new class of treatments focused on genetic therapy to delete the vital 32 amino acids from Ccr5 receptors, elicit perforin and granzyme B production, and organize protease inhibitors to furnish immunity to Hiv and halt its spread may be developed in the future.
Though still a long way off and potentially very expensive (up to ,000 per treatment), Drugs.com Med News reported in Gene Therapy Shows Promise Against Hiv (19 February 2010) that when researchers removed immune cells from eight Hiv-infected persons, modified their genetic code and reinserted them, the "levels of Hiv fell below the thinkable, levels in seven of the eight patients [with] signs of the virus disappear[ing] altogether in one" even though Haart medicine was halted. A study by Ucla Aids organize researchers, which removed Ccr5 receptors by "transplanting a small Rna molecule known as short hairpin Rna (shRna), which induced Rna interference into human stem cells to inhibit the expression of Ccr5 in human immune cells" mimicking those of Ltnps through the use of "a humanized mouse model," as reported on February 26, 2010 in healing News Today in Gene-Based Stem Cell Therapy Specifically Removes Cell Receptor That Attracts Hiv, showed similar success in that it resulted in a "stable, long-term discount of Ccr5."
At the same time, as announced in Hiv/Aids drug puzzle cracked (Kate Kelland, Reuters, 1 February 2010), British and U.S. Scientists succeeded (after 40,000 unsuccessful attempts) in growing a crystal to decipher the buildings of integrase, an enzyme found in Hiv and other retroviruses. This will lead to a great understanding how integrase-inhibitor drugs work and possibly to a more effective generation of treatments that could impede Hiv from pasting a copy of its genetic code in the Dna of victims' T-4(Cd4) cells.
Likewise, per buildings of Hiv coat may help organize new drugs (Health News, 13 November 2009) scientists from the University of Pittsburgh School of medicine "unraveled the complicated structure" of the capsid coat (viewing its "overall shape and atomic details") "surrounding Hiv" that could enable "scientists to organize therapeutic compounds" to block infection.
At the same time, researchers at the University of Texas healing School may have finally discovered Hiv's vulnerability, per Achilles Heel of Hiv Uncovered (Ani, July 2008) - "a tiny stretch of amino acids numbered 421-433 on gp120" that must remain constant to attach to T-4 (Cd4) cells. To conceal its weakness and evade an effective immune response, Hiv tricks the body into attacking its mutating regions, which convert so rapidly, ineffective antibodies are produced until the immune principles is overwhelmed. Based on this finding, the researchers have created an abzyme (an antibody with catalytic or helpful enzymatic activity) derived from blood samples taken from Hiv-negative people with lupus (a chronic autoimmune disease that can attack any part of the body - skin, joints, and/or organs) and Hiv-positive Ltnps, which has proven potent in neutralizing Hiv in lab tests, thus gift promise of developing an effective vaccine or microbicide (gel to safe against sexual transmission). Although human clinical trials are to follow, it might not be until 2015 or 2020 before abzymatic treatments are available.
Elsewhere, International Aids Vaccine Initiative (Iavi) scientists recently isolated two antibodies from a Nltp Hiv-positive African patient - Pg9 and Pg16 (called broadly neutralizing antibodies (Bnabs) that bind to Hiv's viral spike composed of gp120 and gp41 to block the virus from infecting T-4 (Cd4) cells. Per Monica Hoyos Flight, A new starting point for Hiv vaccine organize (Nature Reviews, MacMillan Publishers Limited, November 2009) "Pg9 and Pg16, when tested against a larger panel of viruses [Hiv] neutralized 127 and 116 viruses, respectively" providing supplementary hopes for developing an effective vaccine and novel medicine regimens that induce the body to yield Bnabs, which currently only the immune principles of Nltps can create.
At the same time, studies of newborn seroreversion and medically induced production of human leukocyte group A (Hla) antigens that coat the surface of T-4 (Cd4) cells could also eventually lead to anti-Hiv vaccine that could safe billions of people.
In the meantime until such developments bear fruit, Haart (despite its mild side effects such as nausea and headaches in some and serious to life-threatening side effects in others) has proven to be extremely effective in containing Hiv with, per Gerald Pierone Jr., Md in The End of Hiv Drug development as We Know It? (The Body Pro: The Hiv resource for health Professionals, 18 February 2010) reporting, "about 80% of patients [receiving Haart] reach an undetectable viral load." Furthermore, greater way to antiretrovirals, per Drop in Hiv infections and deaths (Bbc News, 24 November 2009) "has helped cut the death toll from Hiv by more than 10%" from 2004-2008 and saved more than 3 million lives based on Unaids and Who statistics. Haart has also cut the age-adjusted mortality rate by more than 70% according to Kaiser house Foundation's July 2007 Hiv/Aids procedure Fact Sheet, because of its effectiveness in delaying and even preventing the onset of Aids.
Despite Haart's cost (,000-,000 per patient per year), the State of California in a narrative titled, Hiv/Aids in California, 1981-2008 called it "dramatic and life-saving" especially since early intervention results in greater mean T-4 (Cd4) cell counts translating into fewer opportunistic infections and deaths. It also results in real cost savings because of the strong inverse relationship in the middle of T-4 (Cd4) cell counts and linked healing expenses.
In conclusion, despite Hiv/Aids' "disappearing" victims, there is presuppose for optimism. research over the last year has offered some promising leads - the basic cause of Nltps' immunity has been discovered, the buildings of the Hiv virus solved, and its weak point found - while improved way to Haart and Hiv/Aids schooling and arresting measures (with the irregularity of addressing intravenous drug users) have made vital inroads in reducing infection and mortality rates buying victims supplementary years and an enhanced quality of life.
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[1] Orapun Metadilogkul, Vichai Jirathitikal, and Aldar S. Bourinbalar. Serodeconversion of Hiv Antibody-Positive Aids Patients Following medicine with V-1 Immunitor. Journal of Biomedicine and Biotechnology. 7 September 2008.
[2] Michael Crawford. Aids: Where is Our Rage? The Bilerico Project. 2 December 2007. 28 February 2010. Http://www.bilerico.com/2007/12/aids_where_is_our_rage.php
Additional Source:
Wikipedia. 24-28 February 2010. Http://en.wikipedia.org/
Hiv-Aids - Immunity, Eradication and Its Disappearing Victims
Friends Link : hiv antiretroviral drugs
