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, 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, 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,(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.
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