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Winning The Battle Against HIV-1
Winning The Battle Against HIV-1: (MPTV-x , HAART-x) / (MPTV-x , Mega-HAART-x) - Couples Formed of a Multivalent-Polivalent-Therapeutic-Vaccine (MPTV-x) and Its Corresponding HAART-x , or Mega-HAART- Regimen , Respectively. Iosif Secasan Department of Urologic Surgery Spitalul Judetean Resita / The Hospital of Resita RO-1700, Resita Dan I. Pop Data International SRL Str. Horia, Nr.6, Bl.6, Et.10, Ap.39 Resita-1700, RO-1700, Romania Phone: 0040-722-940299 E-mail : danpop77@yahoo.com Ciprian C. Secasan Department of Microbiology / Department of Urologic Surgery Spitalul Judetean Resita / The Hospital of Resita RO-1700, Resita Abstract : This article presents, for the first time in Medical History, an entirely new theory and practical solution to eradicate HIV-1, based on HIV-1's ability and need to mutate under HAART-x / Mega-HAART-x drugs pressure, and on the sinergetical scissoring effect on HIV-1 of (MPTV -x , HAART-x) - couples and (MPTV-x , Mega-HAART-x)-couples, which are formed of : 1. a multivalent-polyvalent-therapeutic-vaccine (MPTV -x) , made of whole-killed HIV-1 (or of particular parts of HIV-1) bearing on its genome (biochemical structure) the resistance-mutations-pattern (RMP-x) that would be induced by the following , to come HAART-x or Mega-HAART-x regimen and of 2. the respective, corresponding HAART-x or Mega-HAART-x regimen, respectively. Key Words : HAART (highly-active-anti-retroviral-therapy), HAART-x regimen, Mega-HAART-x regimen, point-mutations (PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x), resistance-mutations-pattern (RMP-x-), multivalent-polyvalent-therapeutic-vaccine (MPTV -x), (MPTV -x, HAART-x)-couples, (MPTV-x,Mega-HAART-x)-couples, drug-resistant-virus(DRV) , drug-sensitive-virus (DSV); Introduction: Time has come for Science and Medicine to win the battle against HIV and AIDS. This article presents, for the first time in Medical History, an entirely new theory and practical solution to eradicate HIV-1, based on HIV-1's ability and need to mutate under HAART-x / Mega-HAART-x drugs pressure, and on the sinergetical scissoring effect on HIV-1 of (MPTV -x ,HAART-x) - couples and (MPTV-x , Mega-HAART-x)-couples. Since a classical vaccine against HIV-1 is hard to design or even define, and since current HAART (highly-active-anti-retroviral-therapy) and even Mega-HAART regimens are unable to clear an HIV-1 infection , a combined strategy has to be adopted, in order to achieve HIV-1 eradication. This article presents an entirely new theory and practical solution to eradicate the HIV-1 virus from the body of HIV-1 infected persons, by combining HAART (or Mega-HAART) with a multivalent-polivalent -therapeutic-vaccine (MPTV), pre-administrated to HAART, (or Mega-HAART respectively) and targeted against the in-advance-known resistance-mutations-sites (RMS) / resistance-mutations-loci (RML) / point mutations(PM) or even against entire resistance-mutations-pattern(s) (RMP-s) of the following , to come HAART or Mega-HAART regimen, respectively. The polivalent, multivalent, or multivalent-polivalent therapeutic vaccine (PTV-x, MTV-x, MPTV-x) made of killed/highly inactivated HIV-1, bearing on its genome blueprint the resistance-mutations-loci (RML-x)/resistance-mutations-sites (RMS-x), the point-mutations(PM-x), or the whole resistance-mutations-pattern (RMP-x) that would be generated by the following , to come , HAART-x , is pre- administrated to HAART-x, and forms a couple with it : (MPTV -x, HAART-x) or (MPTV-x, Mega-HAART-x) , respectively. A series, or repeated cycles of (MPTV -x, HAART-x) couples, each couple encompassing a multivalent-polivalent-therapeutic-vaccine (MPTV -x) targeted against/ or encoding /or containing /the in - advance - known resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x) , point-mutations(PM-x), or the whole resistance-mutations-pattern (RMP-x) of the following, to come HAART-x - regimen (or Mega-HAART-x -regimen , respectively) may lead to the eradication of HIV-1 from the body of a HIV-1 positive person. The expansion of such a successful HIV-1 eradication therapy may save all 40-50 million persons who are HIV-infected worldwide and would solve the HIV/AIDS crisis. Materials and Methods : The general HIV-1 eradication scheme in a series and/or multi-cycle scenario is : (MPTV-1, HAART-1), ----.> (MPTV-2, HAART-2), ----> (MPTV-3,HAART-3),---->........(MPTV-x, HAART-x)........---->(MPTV-n, HAART-n) -----> --->(MPTV-1M, Mega-HAART-1),---->( MPTV-2M, Mega-HAART-2), ---->(MPTV-3M, Mega-HAART-3)---->....( MPTV-xM, Mega-HAART-x), ....---->(MPTV-nM, Mega-HAART-n)---> -----> Eradication clearly indicating that each multivalent, polivalent, or multivalent-polivalent-therapeutic-vaccine (MPTV-x) is pre-administrated to / (precedes) its corresponding HAART-x - regimen (or Mega-HAART-x - regimen respectively), and is targeted against ( or encodes/or contains) the in -advance-known resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x), point-mutations(PM-x), or even the whole resistance-mutations-pattern (RMP-x) that would be generated by the following , to come HAART-x - regimen (or Mega-HAART-x-regimen, respectively) on HIV-1's genome blueprint. In other words, MPTV-x is preventing the emergence of HAART-x - resistant - virus, acting in fact like a typical VACCINE against the HIV-1 virus that would otherwise emerge after HAART-x therapy. While MPTV-x is preventing the emergence of HAART-x - resistant - virus, HAART-x is reducing viral load, i.e. the numbers of drug-sensitive- virus (DSV). The synergetic scissoring effect of a (MPTV-x,HAART-x) -couple on HIV-1 may be 1000 or even 10.000 times (3-4 Log) more effective and potent than any current HAART-x - regimen given alone, especially in terms of reducing HIV-1 viral load. Considering that a typical HAART-x regimen is currently able to reduce HIV-1 viral load from 60.000 copies/ml or higher, to 20 copies/ml or lower, a (MPTV-x, HAART-x)-couple might be able to reduce viral loads from 60.000 copies/ml or higher to 2-20 copies/litre, whereas a succession of different (MPTV-x, HAART-x)-couples, may lead to eradication of HIV-1 from the body of HIV-1 positive persons. In order to better illustrate the potential anti-HIV-1 power of couples formed by a multivalent-polivalent therapeutic vaccine (MPTV-x) and its corresponding HAART-x - regimen , it can be estimated that a single antiretroviral drug like AZT, (or e.g. Crixivan) , would be as effective as 3-4 antiretroviral drugs ( i.e. as effective as HAART ), provided that it is preceded by a multivalent-polivalent-therapeutic-vaccine (MPTV-x) containing killed HIV-1 (or particular parts of HIV-1) bearing on its genome (biochemical structure) the resistance-mutations-pattern(RMP) of AZT. Figure1/Table1 presents the RMS/RML for different antiretroviral drugs and for 2 drug combinations, i.e. their " point-mutations". The "point-mutations" induced by a particular drug form/build the resistance-mutations-pattern(RMP) of HIV-1 to that drug. Figure1/Table1 Drug Class Primary Resistance Mutations Mutations With Additional Effect RTIs AZT (Retrovir®) M41L, T215Y, T215H D67N, K70R, K219Q, K219E 3TC (Epivir®) M184V, M184T, M184I ddI (Videx®) L74V K65R, L74V, V75T, M184V ddC (HIVID) K65R T69D, L74V, V75T, MI84V, Y215C Abacavir (Ziagen) K65R, L74V, Y115F, M184V D4T (Zerit®) V75T 150T PFA E89G, E89K, L921 W88G, W88S, S156A, Q161L, H208Y NNRTIs Nevirapine (Viramune®) K103N, Y181C, Y181I A98G, L100I, V106A, V108I, Y188C, G190A Delavirdine (Rescriptor®) K103N, K103T, Y181C P23L Efavirenz (Sustiva) Y188L L100I, K101E, K103N, V108I, V179D, Y181C Protease Inhibitors Indinavir (Crixivan®) M46I, M46L, V82A, I84V L10I, L10R, K20M, K20R, L24I, V32I, I54V, A71V, A71T, L90M Nelfinavir (Viracept®) D30N, M46I, A71V, I84V M36I, V77I, N88D, L90M Saquinavir (Fortavase®) G48V, L90M L10I, I54V, I84V Ritonavir (Norvir®) V82A, V82F, V82S, I84V K20R, L33F, M46I, I54L, I54V, A71T, A71V, L90M Resistance to Multiple Drugs AZT + ddI/ddC A62V, V75I, F77L, F116Y Q151M (all 4 mutations required for significant resistance) AZT + 3TC M184V + R211K + L214F G333D, G333E A large database containing nearly all published HIV-1 reverse-transcriptase and protease sequences, and that allows for mutations searching can be found at : http://hivdb.stanford.edu/ HIV-1 recombination and mutation (1-6), including "resistance-mutation", are important mechanisms by which HIV-1 evades drug or immune pressures. HIV-1- strains that are resistant to an antiretroviral drug present multiple " point-mutations"(PM), which act in synergy to confer the resistant phenotype to that drug, and we may define these "point-mutations" (PM-x) as resistance-mutations-loci (RML-x) or resistance-mutations-sites (RMS-x), whereas their ensemble may be termed resistance-mutations-pattern (RMP-x). Multidrug resistant HIV-1 strains arise in patients treated with HAART-x or Mega-HAART-x, either through direct mutation or through recombination of variants that are resistant to single drugs. Paradoxically, and luckily at the same time, point-mutations (PM) that confer drug - resistance offer us targets for vaccine(s) and especially for therapeutic vaccines(TV-s) development. The drug-induced point-mutations (PM), or resistance-mutations-loci (RML-x)/resistance-mutations-sites (RMSx), or even the entire resistance-mutations-patterns (RMP-x-s) may be contained/encoded/encompassed in a multivalent, polivalent or multivalent-polivalent-therapeutic-vaccine (MPTV-x) aimed to prevent the emergence of HAART-x - resistant HIV-1 virus. In HIV-1 infection, the infected hosts apparently cannot solve the problem of identifying an antigen that is conserved among the variants and quasispecies, and thereby neutralize the infection. Paradoxically and luckily again, both HAART and Mega-HAART regimens are not only reducing HIV-1 viral loads to 50 copies/ml or less, but are also UNIFYING HIV-1's diversity, by "artificially" creating a common factor among the remaining/surviving 50 copies/ml of drug-resistant-virus(DRV), in form of resistance-mutations-loci (RML-x) / resistance-mutations-sites (RMS-x) or point-mutations (PM), which together build the resistance-mutations-pattern (RMP-x). Each point-mutation (PM) taken separately, and even entire resistance-mutations-patterns (RMP-x-s) are both excellent targets for therapeutic vaccines (TV), and at the same time can be used as a simple, or polyvalent, or multivalent, or multivalent-polyvalent -therapeutic- vaccines (MPTV -x) respectively, namely in form of whole-killed or highly - inactivated HIV-1 virus (Remune-like and/or Remune- modified bearing the HAART-x or Mega-HAART-x mutations ) , bearing on its genome blueprint the resistance-mutations-pattern(s) (RMP-x-s) of the following , next , to come HAART-x or Mega-HAART-x - regimen. Interestingly and noteworthy, within each (MPTV -x, HAART-x)-couple, and by analogy within each (MPTV-x,Mega-HAART-x)-couple, the multivalent-polyvalent therapeutic vaccine (MPTV -x) acts in fact like a true vaccine, like a CLASSICAL VACCINE against the HAART-x-resistant HIV-1 virus (or Mega-HAART-x- resistant HIV-1 virus), by preventing its emergence. Each antiretroviral drug and each HAART-x - or Mega-HAART-x - regimen divides the HIV-1 viral population in : 1. drug-sensitive-virus (DSV) , which is killed off by HAART-x or Mega-HAART-x respectively, and 2. drug-resistant-virus(DRV), whose emergence can be prevented by the multivalent-polyvalent therapeutic vaccine (MPTV -x) which is pre-administrated to its corresponding HAART-x regimen or Mega-HAART-x regimen, respectively. If a pre - HAART-x administrated multivalent-polyvalent therapeutic vaccine (MPTV -x) manages to prevent the emergence of drug-resistant-virus(DRV), HIV-1 can be eradicated , since the following HAART-x-regimen will eliminate the drug-sensitive- virus(DSV). Results : Infection and immunity are two sides of the same coin. Therefore it is reasonable and scientifically sound to vaccinate an HIV-1 positive person with killed HIV-1 virus resistant to a specific HAART-x regimen, before HAART-x treatment ; and with killed wild-type HIV-1 (eventually collected from the patients' blood before HAART-x treatments onset) at the end of all HAART-x or Mega-HAART-x therapies, especially when a long-term structured -treatment - interruption (STI) is planned or intended. This vaccination with whole, killed, wild-type HIV-1 virus should be done shortly before HAART-x or Mega-HAART-x therapy is stopped ( or interrupted ), since it is well known that some wild-type HIV-1 may still be hidden in certain organs or tissue reservoirs and since it is also well-known that eventually surviving HAART-resistant- HIV-1 virus tends to revert to wild-type HIV-1 virus , after HAART-treatment is stopped. Two Latin sayings describe the rationale of using (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples in eradication of HIV-1. "Divide et Impera" perfectly describes the role and action of HAART-x and Mega-HAART-x regimens, which divide the HIV-1 viral population in drug-sensitive-virus(DSV), which is eliminated/cleared by HAART-x and Mega-HAART-x -regimens respectively, and drug-resistant-virus(DRV) , whose emergence is prevented by the multivalent-polyvalent therapeutic vaccine (MPTV -x) which is pre-administrated to HAART-x or Mega-HAART-x respectively, according to the main principle of prevention, vaccination and homeopathy "Similia Similibus Curentur". The golden standard for multivalent-polyvalent therapeutic vaccines (MPTV-x)-s to be used in (MPTV -x, HAART-x)-couples or (MPTV -x,Mega-HAART-x)-couples, should be whole , killed HIV-1 virus or whole, highly inactivated HIV-1 virus (e.g. Remune-like and Remune-RMP-x- modified), bearing on its genome blueprint the resistance-mutations-pattern(s) (RMP-x-s), that would be generated by the following, to come HAART-x-regimen. On the other hand, the ultimate aim of pathogen (HIV-1) -genome sequencing is the development of vaccines. The genome sequence is the"parts list", and each gene or gene product should be tested for its potential usefulness in anti-HIV-1 vaccine and therapeutic vaccine development. The process of HIV-1 eradication may be divided in 3 steps by monitoring HIV-1 viral load decreases : STEP 1 would mean a viral load decrease from 60.000copies/ml or highr to 5-50 copies/ml; STEP 2 would mean a viral load decrease from 5-50 copies/ml to 5-50 copies/litre and STEP 3 would mean a further viral load decrease from 5-50 copies/litre to zero copies/litre, i.e. eradication of HIV-1. Current HAART and Mega-HAART-x regimens make STEP1 possible for prolonged periods of time. STEP 2 and STEP 3 can only be accomplished by using (MPTV -x, HAART-x)-couples and/or (MPTV -x, Mega-HAART-x) -couples in series and / or cycles. (MPTV -x) , the multivalent-polyvalent therapeutic vaccines, can be defined and designed in many ways, depending on the drugs that are chosen as partners in the (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples. When a combination of reverse-transcriptase inhibitors (RTI-s) is chosen as a first-line drug - treatment,(MPTV -x) may contain at least 2 main components : 1. whole killed HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase inhibitor and of their combination (Figure1/Table1) and 2. an HIV-1 reverse-transcriptase enzyme bearing the point-mutations of the following, to come, to be used reverse-transcriptase inhibitors (RTI-s). When a combination of protease inhibitors is chosen, ,(MPTV-x) may also have 2 main components: 1. whole killed HIV-1 virus bearing the point-mutations (PM) of each protease inhibitor and of their combination(Figure1/Table1) and 2. an HIV-1 protease enzyme bearing the point-mutations (PM) that would be induced by the following, to come protease inhibitors (PI-s) in the absence of pre-administrated MPTV -x. When a combination of reverse-transcriptase and protease - inhibitors is chosen as the HAART-x component of the (MPTV-x, HAART-x)-couple, MPTV -x may contain at least 3 main components : 1. whole killed / inactivated HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase and of each protease inhibitor (Figure1/Table1), as well as the point-mutations (PM) with additional effect; 2.an HIV-1 reverse-transcriptase bearing the point-mutations (PM) that would be induced by the reverse-transcriptase inhibitors (RTI-s) to come; 3. an HIV-1 protease enzyme, bearing the point-mutations (PM) that would be induced by the following, to come, to be used protease inhibitors. In addition to the reverse-transcriptase inhibitors (RTI-s) and protease inhibitors(PI-s), fusion inhibitors like T 20 and T-1249, and integrase inhibitors like S-1360 and L870,810 (7) may be soon added to current HAART-x and Mega-HAART-x regimens. ( The integrase enzyme is essential for HIV to integrate its proviral DNA into the host cell chromosome. S-1360 ,e.g., , is a low molecular weight molecule, for oral use, that inhibits the integrase enzyme in HIV-1.) An HIV-1 integrase- enzyme, bearing the point-mutations (PM), that would be induced in HIV-1-s genome by integrase inhibitors (II), may be introduced as a fourth component of a multivalent-polyvalent therapeutic vaccine (MPTV -x) against HIV-1, along with : 1. whole killed/inactivated HIV-1 virus bearing the point-mutations (PM) of each reverse-transcriptase inhibitor, of each protease inhibitor (Figure1/Table1), and of each integrase inhibitor , as well as the point-mutations (PM) with additional effect; 2. An HIV-1 reverse-transcriptase bearing the point-mutations (PM) , RMS/RML -s that would be induced by the reverse-transcriptase- inibitors (RTI-s) to come; 3.An HIV-1 protease bearing the point-mutations(PM) ,RMS/RML, and even the whole RMP that would be induced by the following, to come protease inhibitors. Most importantly in this article , the multivalent-polyvalent therapeutic vaccines (MPTV -x) may be defined and consist minimally of 3 enzymes : 1. an HIV-1 reverse-transcriptase enzyme, 2. an HIV-1 protease enzyme and 3. an HIV-1 integrase enzyme , each of the 3 enzymes bearing the point-mutations (PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x) or even the entire resistance-mutations-patterns (RMP-x-s) of the following , to come HAART-x regimen or Mega-HAART-x regimen, respectively. The rationale to use the 3 viral enzymes : reverse-transcriptase, protease and integrase as components of a multivalent-polyvalent therapeutic vaccine (MPTV -x) against HIV-1 is based on the fact that all currently approved antiretroviral drugs are either reverse-transcriptase inhibitors, or protease inhibitors or integrase inhibitors, and only these drugs are able to generate HIV-1 strains bearing on their genomes the point-mutations(PM), resistance-mutations-loci (RML-x), resistance-mutations-sites (RMS-x), resistance-mutations-patterns (RMP-x-s) listed in Table1/Figure1. Discussion : This entirely new approach to treat HIV-1 infections with (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples, can be adapted and used to treat all possible hard - to - treat infectious diseases for which at least one effective drug has been developed, and may lead to the eradication of many (otherwise resistant) microbes, pathogens, viruses and fungi from the body of infected persons. Especially hard- to- treat infectious diseases, like tuberculosis (TB) and malaria , may be eradicated and drug-resistant pathogens eliminated when (MPTV -x, drugs-x ) -couples are carefully and wisely selected and used rationally. This (MPTV -x, HAART-x)-couple-approach may also be used in the treatment of cancer. In cancer, the role of the MPTV -x can be taken by killed cancer cells bearing on their DNA the mutation-points(PM) of the anti-cancer drugs to be used in chemotherapy. Conclusions : An entire industry of multivalent therapeutic vaccines (MTV-x), polivalent therapeutic vaccines (PTV-x), and, of course, multivalent-polyvalent therapeutic vaccines (MPTV-x)-s against HIV-1 will probably emerge after the publication of this article. These multivalent-polyvalent therapeutic vaccines (MPTV-x)-s will be used together with their corresponding HAART-x and Mega-HAART-x regimens in (MPTV -x,HAART-x)-couples and (MPTV -x,Mega-HAART-x)-couples, respectively, Using an "ad conventium" terminology, a polivalent therapeutic vaccine (PTV-x) should have the capacity to prevent the emergence of the primary resistance-mutations-pattern (RMP) for at least one antiretroviral drug and up to a HAART or Mega-HAART -regimen. A multivalent therapeutic vaccine (MTV-x) should have the capacity to prevent the emergence of at least 2 successive resistance-mutations-patterns (RMP-s) for at least one drug, and up to a HAART or Mega-HAART -regimen, whereas a multivalent-polyvalent therapeutic vaccine (MPTV -x) should be able to prevent the emergence of primary , secondary and even multiple successive HIV-1 resistance-mutations-patterns (RMP-s) for a HAART or Mega-HAART - regimen. Ideally, a multivalent-polyvalent therapeutic vaccine (MPTV -x) should be able to prevent the emergence of a very high or even unlimited number of successive resistance-mutations-patterns (RMP-s) and/or it should be able eradicate HIV-1 by acting sinergetically with their corresponding HAART-x or Mega-HAART-x regimens, within these (MPTV -x, HAART-x)-couples, or (MPTV-x, Mega-HAART-x)-couples, respectively. ADVENTRX Pharmaceuticals intends to begin human trials for EradicAide (8) , an HIV therapeutic vaccine, composed of six synthetic peptides, which stimulate a killer T-cell response to clear HIV-infected cells. A unique feature of this treatment is that it is designed to not elicit an antibody response. It is antibody-negative. Such a therapeutic vaccine may also be added to (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples , as an adjuvant therapeutic vaccine(ATV) to (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples, respectively. Also, the Remune vaccine of the The Immune Response Corporation, Inc. (9) may be considered ( and used ) as an adjuvant therapeutic vaccine(ATV) to (MPTV -x, HAART-x)-couples and to (MPTV-x,Mega-HAART-x)-couples . Studies have shown that inactivated, gp120-depleted whole virus immunogen (Remune) boosts immune responses to HIV-1. Both therapeutic vaccines (TV) mentioned above , (EradicAide and Remune), as well as others that are in advanced development and clinical trials, may eventually be adjusted, modified and adapted to be used in one formulation prior to HAART-x (or Mega-Haart-x) onset, and in a different formulation during HAART-x or Mega-Haart-x treatment. In other words, they may be used both in (MPTV -x, HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples , and/or as adjuvant therapeutic vaccines(ATV). Affymetrix (10) , a leading US company in DNA-chip technology has developed GeneChip oligonucleotide probe arrays that are manufactured using a high resolution photolitographic fabrication process adapted from the semiconductor industry, for HIV-1 mutations determinations. The Authors of this article believe that an entire industry of standardized multivalent-polyvalent therapeutic vaccines (SMPTV-x)-s will emerge, to act complementary and sinergetically with HAART-x and/or Mega-HAART-x - regimens in order to eradicate HIV-1. The Authors of this article are very interested to collaborate with pharmaceutical companies interested to produce (SMPTV -x)-s for use in (MPTV -x, HAART-x) -couples and (MPTV -x , Mega-HAART-x)-couples aimed and designed to eradicate HIV-1, cancer (11) , and other infectious diseases. References: 1. Hahn B.H. , Robertson D.L. , McCutchan F.E. , Sharp P.M. , Recombination and diversity of HIV: implications for vaccine development. Neuvieme Colloque Des Cent Gardes , 1994, 87-94 ; 2. Robertson D.L. , Sharp P.M. , McCutchan F.E. , Hahn B.H. , Recombination in HIV-1, Nature 1995 : 374 :124-126; 3. Robertson D.L. , Hahn B.H. , Sharp P.M. , Recombination in Aids viruses, J.Mol.Evolution , 1995, 40, 249-259; 4. Sharp P.M., Robertson D.L., Hahn B.H. , Cross - species transmission and recombination of ' AIDS ' viruses. , Phil. Trans. R. Soc., London B , 1995, 349 : 41-47; 5. M. L. Kalish et al, Recombinant Viruses and Early Global HIV-1 Epidemic, Emerging Infectious Diseases, Vol.10, No.7, July 2004; 6. I.S. Secasan, D.I. Pop , Fighting HIV with HIV, Medical Hypotheses,1998 Jan;50(1):39-42 Churchill-Livingstone, ISSN 0306-9877; 7. Young, S.D., et al. L870,810: Discovery of a potent HIV integrase inhibitor with potential clinical utility, Presented at The XIV International AIDS, Conference, Barcelona, Spain. 8. http://www.adventrx.com/products/antiv_eradicaide.htm 9. http://www.imnr.com : The Immune Response Corporation, Inc. web-site 10. http://www.affymetrix.com/index.affx 11. Iosif Secasan, Dan I. Pop, Ciprian C. Secasan: Potentially New And Innovative Treatments For Superficial, Muscle-Invasive, And Metastatic Transitional Cell Carcinoma (TCC) Of The Bladder. The Internet Journal of Oncology. 2005. Volume 2 Number 2.
About the Author
Iosif Secasan
Department of Urologic Surgery
Spitalul Judetean Resita / The Hospital of Resita
RO-1700, Resita
Dan I. Pop
Data International SRL
Str. Horia, Nr.6, Bl.6, Et.10, Ap.39 Resita-1700,
RO-1700, Romania
Phone: 0040-722-940299 E-mail : danpop77@yahoo.com
Ciprian C. Secasan
Department of Microbiology / Department of Urologic
Surgery
Spitalul Judetean Resita / The Hospital of Resita
RO-1700, Resita
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