Winning The Battle Against HIV-1

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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. 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
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    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.
     
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