# Serodeconversion of HIV Antibody-Positive AIDS Patients Following Treatment with V-1 Immunitor

Authors: Orapun Metadilogkul; Vichai  Jirathitikal; Aldar S. Bourinbaiar
Journal: Journal of Biomedicine and Biotechnology
 (2009)

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## Abstract

It is extremely rare when HIV seropositive adult patients experience spontaneous loss
of antibodies, that is, seroreversion. The disappearance of HIV antibodies was occasionally
attributed to iatrogenic interventionserodeconversion. Such interventions include:
HAART; oral interferon; Chinese herbal remedies; and therapeutic AIDS vaccines
derived from pooled blood. Oral therapeutic, alloimmune AIDS vaccine, V-1 Immunitor
(V1), was administered to 60000 HIV-positive Thai patients. The administration of V1
resulted in serodeconversion among 23 individuals. The patient group consisted of 9
females (39%) and 14 males (61%) including two 2-year-old boys. The age range was
2–58 years with mean/median 29/29.3 years. Patients were tested seropositive for HIV
at least once before being enrolled on V1. The duration of treatment until discovery of
seronegative status ranged between 2 weeks and 15 months with average/median 7.2/8
months. Time to seronegativity was correlated with baseline disease stage (R=0.62; P=.002). The seronegative status was positively associated with V1-induced
undetectable or low viral load (R=0.65; P=.0008). The odds ratio analysis comparing
the outcome of our study with published surveys of diagnostic accuracy of laboratory
tests suggested that the probability of HIV antibody testing error was remote
(P<.000001). The possible causes responsible for this unusual phenomenon are
discussed.


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## Body

## 1. Introduction

The HIV seropositivity revealed by an antibody test is indicative of virus
infection. Due to a small proportion of false-positive, false-negative, and
ambiguous (indeterminate) findings occurring in a general population, this test
is not perfect but remains, however, the first-line laboratory procedure for
diagnostic purposes. It is currently accepted that antibody tests are nearly
100% sensitive and about 99% specific [1, 2]. The frequency of false-positive
HIV serology in a low-prevalence population, for example, military recruits
from rural United States, is 1/135 000 [1], while for blood donors in Minnesota
is 6/million [2]. A survey of 5 million blood donors' samples found that the
prevalence of false positives was 1/251 000 [1]. To reduce the chances of
technical or clerical error, the antibody tests are confirmed by additional
tests like ELISA, western blot, and PCR analysis. When tests are combined, for
example, ELISA and western blot, the false-positive rate has been reported to
be as low as 1/100 000 [3]. Others have indicated that even when tests are
combined, about 3% of the investigated sera were false-positive,
false-negative, or noninterpretable [4].It is extremely unusual when symptomatic or
asymptomatic individuals with culture- or PCR-confirmed HIV infection do not
produce virus-directed antibodies and remain persistently negative beyond the
expected window period. A few such cases have been reported in the literature, and
most of which were due to agammaglobulinemia of unknown immune dysfunction [5–11].
These exceptions only reinforce the general notion that once a person is
diagnosed with HIV, he or she remains antibody-positive for the rest of his or
her life.Newborn babies usually lose HIV antibodies acquired
from their HIV-positive mothers. The average time to seroreversion after birth is
usually 12–16—maximum 18
months [12]. However, with the exception of very few instances, these infants
are not HIV-infected [13]. An adult with confirmed HIV infection seldom changes
seropositive status. Occasionally, this has been observed among individuals who
were at the terminal stage of disease [14, 15]. Cases of spontaneous
seroreversion among patients from other categories are exceedingly rare [16–18].In addition to cases of spontaneous loss of
antibodies, there are several reports attributing this phenomenon to iatrogenic
intervention, referred to as serodeconversion. The earliest known report is
related to administration of low-dose oral interferon, whereby 18 out of 204 treated
patients became HIV-negative [19]. A clinical study of Chinese herbal
preparations revealed serodeconversion in eight AIDS patients [20]. Two recent
reports have shown for the first time that patients with acute or early HIV
infection may lose HIV antibodies as a result of highly active antiretroviral
therapy [21, 22], supporting the notion that serodeconversion seldom occurs in
patients on antiviral therapy [1]. Finally, both therapeutic AIDS vaccines
produced from the blood of HIV patients, that is, Nigerian Abalaka's vaccine
and Cameroonian Anomah Ngu's vaccine, were reported to produce serodeconversion
in several dozen AIDS patients [23, 24].V-1 Immunitor (V1)—the first
commercial therapeutic AIDS vaccine—has been registered
by the Thai FDA as a food supplement and experimental drug [25]. The vaccine
comprises heat-inactivated HIV antigens derived from pooled blood of
HIV-infected donors. Extensive preclinical studies have shown that V1 is safe [25].
In a longitudinal survey in 400 patients, about 85% reported improvement, 6%
reported no difference, and 9% reported minor adverse reactions, which did not
last more than one week [26]. Our earlier open-label and subsequent
placebo-controlled clinical studies have shown that V1 administration increases
absolute CD4 and CD8 cell counts in both HIV-positive and HIV-negative subjects
[27–29]. Viral load measurements have shown statistically significant trend
toward decrease [27]. Other clinical benefits included the reversal of
AIDS-associated wasting and normalization of elevated liver enzymes in
HIV-positive patients coinfected with hepatitis viruses [26]. Patients on V1
rarely develop new fungal or bacterial infections, suggesting that V1 restores
the mucosal immune response to opportunistic infections [26]. Finally, in a
survival study, the end-stage AIDS patients had 15.8 times longer life
expectancy than those who declined V1 treatment [30]. This single clinical
endpoint is clearly more important than surrogate endpoints such as viral load
and T-cell counts. In this study, we analyze yet another phenomenon associated
with V1 therapy, that is, an observation that some AIDS patients who received
V1 became HIV-antibody-negative.


## 2. Materials and Methods

### 2.1. Patients

Sixty thousand patients from Thailand with documented history of HIV infection have received or are currently
receiving V1. In this retrospective survey, every patient who became aware of
HIV-antibody-negative status following treatment with V1 was considered for the
analysis. Patients who did not have reliable antibody test, traceable to the
original issuing lab, were not included and only those with confirmed
serodeconversion as compared to baseline status were included in this survey.
The physical examination and patients' interviews were performed at Rajavithi General Hospital
in Bangkok. Patients self-administered either one or two V1 tablets per day. The dose for
children was twice smaller. With the exception of one patient (no. 22), none of
them received conventional antiretroviral therapy or participated in any AIDS
vaccine trials conducted in Thailand during treatment period. Patient no. 22, a two-year-old boy
from Tanzania, was on AZT monotherapy for a few months shortly after the birth but due to drug
intolerance and lack of clinical improvement he discontinued treatment before
starting on V1.


### 2.2. Vaccine

V-1 Immunitor (V1) is derived from specially processed heat and chemically inactivated,
pooled blood of HIV-infected Thai donors. The vaccine is formulated into an
oral tablet according to a proprietary process developed by us [25]. As pooled blood
from unrelated donors was used for vaccine manufacturing, V1 can be regarded as
an allovaccine since in addition to viral proteins it also contains
alloantigens from the blood. The vaccine is manufactured in Thailand by Immunitor (Thailand) Co., Ltd., and is
approved by Thai Food and Drug Administration (FDA) as
a dietary supplement and investigational drug. V-1 Immunitor is provided as 850
mg coated tablet—ten of which are
sealed in a “blister” package (Figure 1).Figure 1
The
appearance of V-1 Immunitor (V1) therapeutic oral AIDS vaccine.


### 2.3. HIV Tests

Most of patients' sera were examined by rapid tests for HIV antibodies (Bioline
HIV1/2, Immunochemical Lab, Thailand and Determine HIV1/2 Abbott/Dainabot, Japan).
Another approved antibody test used in Thailand as a second-line test is ELISA
or enzyme immunoassay (EIA). These tests are also commercially available: Uni-Form
II Ag/Ab kit (Organon Technika, The Netherlands) or HIV1/2
(Abbott Laboratories, USA). Occasionally, latex
particle agglutination test (GPA, Serodia-HIV 1/2, Fujirebio Inc., Japan)
was utilized as an alternative to ELISA. The choice of second-line tests depended
on their availability at the testing lab and patients' ability to pay for them.
In some cases, commercial western blot assay was conducted in addition to
antibody tests (HIV Blot 2.2, Genelabs Diagnostics, Singapore).
As tests were performed in different labs, the QA/QC standards may vary but
these variables were beyond our control due to retrospective nature of this
study.


### 2.4. Viral Load Measurement

Plasma viral concentrations were measured at various independent hospitals and
commercial labs at patients' own choice. As PCR tests are expensive, very few
patients were able to afford such tests. Depending on the individual lab, the commercial
viral load kits were used without any specific preference. These quantitative PCR
kits were either RNA PCR kit (Roche Diagnostic Systems, Inc., Branchburg, NJ, USA)
or branched DNA kit (Bayer, Tarrytown, NJ, USA).
The sensitivities of these tests were 400 and 50 viral copies per mL, respectively.
In addition, qualitative tests for HIV-1 were performed by in-house developed
PCR method according to our own published protocol [31]. The lowest detection
threshold of this test was estimated to be not less than 100 HIV copies per mL.


### 2.5. Statistical Analysis

Data were analyzed with StatMost software version 2.5 (DataMost Corporation,
Salt Lake City, Utah, USA) and SISA—free online program—with courtesy of
Daan Uitenbroek. The main parametric pairwise test was Student'st-test.
The odds ratio (OR) was estimated at 95% Wald confidence interval (CI). For assessment
of correlation between seronegative status and viral load, we have used nonparametric
Spearman's rank-order test. The significance level for all tests was set
at P≤.05.


## 2.1. Patients

Sixty thousand patients from Thailand with documented history of HIV infection have received or are currently
receiving V1. In this retrospective survey, every patient who became aware of
HIV-antibody-negative status following treatment with V1 was considered for the
analysis. Patients who did not have reliable antibody test, traceable to the
original issuing lab, were not included and only those with confirmed
serodeconversion as compared to baseline status were included in this survey.
The physical examination and patients' interviews were performed at Rajavithi General Hospital
in Bangkok. Patients self-administered either one or two V1 tablets per day. The dose for
children was twice smaller. With the exception of one patient (no. 22), none of
them received conventional antiretroviral therapy or participated in any AIDS
vaccine trials conducted in Thailand during treatment period. Patient no. 22, a two-year-old boy
from Tanzania, was on AZT monotherapy for a few months shortly after the birth but due to drug
intolerance and lack of clinical improvement he discontinued treatment before
starting on V1.


## 2.2. Vaccine

V-1 Immunitor (V1) is derived from specially processed heat and chemically inactivated,
pooled blood of HIV-infected Thai donors. The vaccine is formulated into an
oral tablet according to a proprietary process developed by us [25]. As pooled blood
from unrelated donors was used for vaccine manufacturing, V1 can be regarded as
an allovaccine since in addition to viral proteins it also contains
alloantigens from the blood. The vaccine is manufactured in Thailand by Immunitor (Thailand) Co., Ltd., and is
approved by Thai Food and Drug Administration (FDA) as
a dietary supplement and investigational drug. V-1 Immunitor is provided as 850
mg coated tablet—ten of which are
sealed in a “blister” package (Figure 1).Figure 1
The
appearance of V-1 Immunitor (V1) therapeutic oral AIDS vaccine.


## 2.3. HIV Tests

Most of patients' sera were examined by rapid tests for HIV antibodies (Bioline
HIV1/2, Immunochemical Lab, Thailand and Determine HIV1/2 Abbott/Dainabot, Japan).
Another approved antibody test used in Thailand as a second-line test is ELISA
or enzyme immunoassay (EIA). These tests are also commercially available: Uni-Form
II Ag/Ab kit (Organon Technika, The Netherlands) or HIV1/2
(Abbott Laboratories, USA). Occasionally, latex
particle agglutination test (GPA, Serodia-HIV 1/2, Fujirebio Inc., Japan)
was utilized as an alternative to ELISA. The choice of second-line tests depended
on their availability at the testing lab and patients' ability to pay for them.
In some cases, commercial western blot assay was conducted in addition to
antibody tests (HIV Blot 2.2, Genelabs Diagnostics, Singapore).
As tests were performed in different labs, the QA/QC standards may vary but
these variables were beyond our control due to retrospective nature of this
study.


## 2.4. Viral Load Measurement

Plasma viral concentrations were measured at various independent hospitals and
commercial labs at patients' own choice. As PCR tests are expensive, very few
patients were able to afford such tests. Depending on the individual lab, the commercial
viral load kits were used without any specific preference. These quantitative PCR
kits were either RNA PCR kit (Roche Diagnostic Systems, Inc., Branchburg, NJ, USA)
or branched DNA kit (Bayer, Tarrytown, NJ, USA).
The sensitivities of these tests were 400 and 50 viral copies per mL, respectively.
In addition, qualitative tests for HIV-1 were performed by in-house developed
PCR method according to our own published protocol [31]. The lowest detection
threshold of this test was estimated to be not less than 100 HIV copies per mL.


## 2.5. Statistical Analysis

Data were analyzed with StatMost software version 2.5 (DataMost Corporation,
Salt Lake City, Utah, USA) and SISA—free online program—with courtesy of
Daan Uitenbroek. The main parametric pairwise test was Student'st-test.
The odds ratio (OR) was estimated at 95% Wald confidence interval (CI). For assessment
of correlation between seronegative status and viral load, we have used nonparametric
Spearman's rank-order test. The significance level for all tests was set
at P≤.05.


## 3. Results

The patient group consisted of 9 females (39%) and 14 males (61%) including 2 two-year-old
boys. Ages ranged within 2–58 years with a
mean age of 29 years (median age = 29.5 years). The duration of V1 treatment
until a patient sought to check the antibody status ranged between 2 weeks and
15 months with an average of 7.2 months (median range = 8 months). All patients
were tested for HIV seropositivity prior to administration of V1. While most of
them were tested only once before treatment initiation, on average, there were
two positive tests per patient. Once patients knew the seronegative status,
many of them had tests repeated, often at different labs to ascertain that they
were truly negative. Thus, the average number of post-treatment tests was
slightly higher (3 tests) but not statistically significant. The results are
summarized in Table1 which shows only those tests for which we have traceable
records.Table 1
Summary of lab tests on serodeconverted HIV-positive patients treated with V1.
No.GenderAgeHIV disease stage as per the WHO criteriaMonths since known as being infected as per patient's recollectionFirst tested positive (m/y)Months on V1HIV positive  timesaHIV negative timesbHIV PCR copies beforecHIV PCR copies afterQualitative PCRd positiveQualitative PCRd negative01F30413/001425617<50202F3820.57/01224<50103F313189/014482104F2441810/0141105F27329/01241183006M263Unknown4/01122<5007F193Unknown6/0111308M284156/021017109M32374/0015110127; 2710<400; <50110F28378/013501140; 16201111F294211/01870<50; <4002212M244245/0211354390013M283122/0291414M304363/02101315M4041203/02101116M58461/0261117M3220.512/010.51118M384962/02111319M434325/02111420M333Unknown5/0231121M24248/02151222M24243/0221323F294Unknown2/021311<400aTests were done at baseline before treatment initiation.
bTests were performed after treatment initiation.
cTests were done after treatment initiation, not at baseline.
dDue to high cost, some patients had qualitative PCR tests, that is,
positive or negative, rather than quantitative ones—all of such tests
were carried out after treatment initiation.At baseline, we had 13 (56.5%) patients who
qualified as having full-blown AIDS, while the remaining 2 (8.7%) and 8 (34.8%)
patients had the WHO stage 2 and 3 symptoms, respectively. Since patients with
fewer symptoms were recovering faster, the correlation analysis was conducted
to see if there is a relation between severity of disease and time to
serodeconversion. The results indicate that earlier you start treatment, faster
you expect to see the disappearance of HIV antibodies (Spearman's rank
correlation,R=0.620793; P=.0015773).In nine patients, viral loads were barely detectable
or undetectable after treatment, but unfortunately four of these patients had no
matching PCR tests at study entry. Qualitative PCR tests which were conducted
at the end of study were either positive or negative. But the majority of
patients had not tested for viral load primarily due to the fact that they
could not afford expensive PCR tests. Nevertheless, from what is available to
us, there is a clear impression that serodeconversion correlates with lowered
or undetectable viral load.Unfortunately, we do not have the complete pairwise
set of data to confirm this impression by a robust parametric test. We thus have
performed nonparametric Spearman's rank order correlation analysis on available
outcome results, that is, nine patients: nos. 1, 2, 3, 6, 8, 9, 10, 11, and 23.
We assume that four patients—nos. 3, 6, 8, and 23—had positive PCR
results prior to the therapy. Each viral load test, whether positive or
negative, was entered as a binary value. For example, patient no. 1 had three
negative results and a total of 3 were entered into negative results' column;
patient no. 3 had 2 negatives and 1 positive reading, which were entered into
negative and positive results' columns, respectively. Patients who had no
results had zeros entered as values. In this manner, we have constructed a two-way
table to evaluate whether HIV-seronegative status had any association with
negative or positive PCR results. The results revealed positive linear
relationship withR=0.64842 at P=.000819. We thus conclude that serodeconversion
correlates positively with low or undetectable viral load.Another reliable test that could be performed on
available data is establishment of the odds ratio, which could tell whether our
findings differ from published incidence of false-positive or false-negative
results in large populations of individuals screened for HIV antibodies. Such a
statistical test was aimed to reveal whether the observed incidence of
serodeconversion, that is, 23 individuals out of 60000, could happen randomly as
a result of laboratory error. This analysis was performed in2×2 contingency
table comparing side by side our data with published surveys of diagnostic
accuracy of HIV tests. The results are presented in Table 2. As can be seen
from Table 2, what we have observed is statistically different in every single
case. All obtained OR values were distant from 1—a ratio that one would
expect to see if there was no difference between our outcome and frequencies reported
by others.Table 2
Odds ratio of observed serodeconversion rate, that is, 23 out of 60,000
patients, in comparison to published incidence rate of erroneous HIV tests.
ReportObservedTotal numberOdds ratio with CI at 95%Two-sidedP value[1]1135 000OR = 0.0193; CI = 0.002–0.1432P<.0000000001[1]1251 000OR = 0.0104; CI = 0.001–0.077P<.0000000001[2]61000 000OR = 0.0157; CI = 0.0064–0.038P<.0000000001[3]1100 000OR = 0.0261; CI = 0.004–0.1932P=.0000000024[4]311032OR = 78.362; CI = 45.53–134.86P<.0000000001[32]12.41000 000OR = 0.0324; CI = 0.0207–0.051P<.0000000001


## 4. Discussion

Due to the retrospective nature of this study, the data, especially concerning
viral load, are incomplete. Nevertheless, it is clear that obtained results are
highly unusual. Why would previously HIV-antibody-positive patients become
seronegative after treatment with V1?The possibility that all these patients were
false-positive at the baseline is unlikely since they were symptomatic and
sought V1 treatment because they were suffering from AIDS-related symptoms. These symptoms, that is, low CD4 counts; weight loss; a whole range of opportunistic
infections: such as oral thrush, TB, skin lesions, persistent diarrhea, and in one case
even Kaposi’s sarcoma, were severe enough to score them as belonging to advanced
disease stage [33].One may argue that clinical symptoms were not HIV-related
and all these patients were initially false-positive due to random incidence of
such cases in general population. This scenario, however, remains highly
unlikely since, according to the “normal” incidence of false positives in healthy
individuals, one would expect no more than 1/4 (0.25%) to 1/2 (0.5%)  false-positive
persons among 60000 V1-treated individuals [1]. On the contrary, in
placebo-controlled, randomized phase II clinical trial of V1 published in 2004,
we have shown that one out of 29 V1-treated patients became HIV-negative,
suggesting much higher conversion rate [29]. The cases of true, confirmed
seroreversion, that is, a seroreactive or positive sample with subsequently one
or more nonreactive samples from the same person, are extremely rare [10–18].
In fact, most, if not all, cases of apparent seroreversion seem to be errors of
attribution or lab testing [1–4]. A survey on 2 580 974 army recruits
identified 4911 seropositive individuals by two independent samples, among whom
only six were potential seroreverters [32]. Further review of these cases
revealed that five actually were HIV-seroreactive patients who had samples from
nonreactive individuals mistakenly attributed to them, while the sixth had a
testing error. Mistakes in the testing process were identified in other 26
cases indicating the cumulative error rate of 12.4 per 1 million individuals.
In this paper, we included only those patients who had confirmed tests
traceable to the original testing lab and excluded anyone who had indeterminate
results or whose records could not be traced. The odds ratio analysis comparing
our data with published reports of false-positive or false-negative cases in
large surveys rules out that what we have observed is a random event due to
testing error (see Table 2).Even the two infants in our study who were born to
HIV-positive mothers are unlikely to be false-positive since they were both
symptomatic and tested repeatedly positive past the age of 18 months, a
timepoint by which the newborns lose maternal antibodies [12, 13]. Table 1,
however, shows only one positive baseline test for each of the boys since other
tests could not be traced to original issuing labs.Another aspect worthy of note is that patient no. 17
tested negative after 2 weeks on V1, whereas patients nos. 6 and 7 became seronegative
after 1 month. As on average, it took 7–8 months and as
long as 15 months to attain seronegative status; the two-week period appears to
be very short. Nevertheless, considering that half life of anti-p24 IgG immunoglobulin
is 11–19 days, it is
possible that HIV antibodies were still present but their levels have decreased
below detection limit of standard assays [34]. This possibility is not entirely
implausible. The antibody tests of some of the patients were fluctuating from
positive to negative and back to positive during the therapy suggesting that the
levels of anti-HIV antibodies were at the borderline of detection threshold. Furthermore,
despite being seronegative, four patients—nos. 3, 9, 10, and 11—were still
showing the presence of the virus as detected by PCR analysis. Latter situation
is reminiscent of extensively studied high-risk seronegative (HRSN) individuals
who have remained HIV-negative despite repeated exposure to the virus. It has
been shown recently that HRSNs often carry extraordinary low levels of HIV-1
DNA [35]. However, as opposed to our patients, these individuals are free of
disease symptoms and are commonly known as long-term survivors.It is not unusual to see the decline in antibodies
in very late stage of HIV disease which may be explained, in part, by higher
viral burden and reduced availability of circulating antibodies due to antibody-antigen
complex formation. In our situation, as there is a documented decrease in viral
burden, we would expect to see a surplus of antibodies rather than their
reduction. Furthermore, time to reach seronegative status was not random. It
was correlated with baseline disease stage, meaning that those who are better
off initially were likely to require less time to convert than those with advanced
disease (R=0.62; P=.002). Incidentally, all three patients—nos. 17, 6, and 7—who converted to
seronegative status under one-month time were all in earlier disease stage.The therapeutic vaccination was first
introduced into clinical practice by the French researcher Daniel Zagury as a
treatment option for AIDS more than 20 years ago [36]. Due to inherent problems
associated with HAART, this concept has become increasingly popular nowadays.
However, nearly 30 therapeutic vaccine candidates were tested in over 60
clinical trials, but they have not produced any evidence of clinical benefit,
let alone serodeconversion [37]. The only exception are pooled blood-derived AIDS vaccines, developed by Drs. Abalaka and Ngu, THIVAC and VANHIVAX, respectively, which produced favorable clinical outcomes and have caused serodeconversion in some of their patients [23, 24]. Their results provide further support to a possibility
that what we have observed with V1 is not due to testing or clerical error.From the immunological point of view,
this phenomenon seems to be related to an observation first made by Stott, who
reported that macaques vaccinated with a preparation of whole killed human
cells infected with SIV were fully protected against subsequent challenge [38].
Curiously, animals immunized with a control preparation consisting of killed
human cells without SIV were also protected. This observation appears to relate
to the fact that during the budding process through the cell membrane, SIV as
well as HIV acquires several hundred host cell molecules [39]. Thus, the
immunization with host's proteins was equal to or more effective than immunization
with viral antigens. While the interpretation of Stott study has been
contested, several studies appear to be in agreement with this seemingly
unusual finding. For example, Lopalco et al. reported that the enigmatic
phenomenon of exposure to HIV without seroconversion was associated with
anticell auto-anti-bodies but not with HIV-neutralizing antibodies directed
against viral antigens [40]. Sera from polytransfused, HIV-negative individuals
who often develop immune responses against themselves,
including anti-HLA antibodies, were shown to neutralize HIV-1 [41].The concept that AIDS is an autoimmune disease and thus alloimmunization or in other
words, immunization with autologous cellular antigens with or without HIV antigens, as a
basis for immune-based therapy of HIV has been advocated at length by us and others [42, 43]. Several therapeutic approaches based on this concept have been
proposed. Daniel Zagury, who pioneered therapeutic HIV immunization, made his original
vaccine from formaldehyde-treated leukocytes derived from the blood of seropositive
patients [36]. His vaccine has shown dramatic clinical improvements, but unfortunately
his work has not been followed. The autologous T-cell vaccination developed by
Abulafia-Lapid et al. has shown encouraging results with over 50% (median of
70%) increase in CD4 cell counts. Their vaccine consists of in vitro propagated,
glutaraldehyde-inactivated, autologous T cells which are injected back to
HIV-positive donors [44]. Remune is another vaccine in this category; however,
due to the purification process of virus particles from the supernatant of cell
culture, it may not possess sufficient quantity of alloantigens, which may
explain persistent incertitude in clinical effect [45]. Oral feeding of alloantigens, as in case of V1, is an approach that makes sense since it induces immune tolerance—a strategy that has been shown effective in therapy of chronic hepatitis B and C—diseases that are caused by autoimmune reaction against virus-carrying liver cells rather than direct cytopathic effect of hepatitis viruses [46–48]. Israeli
et al. have shown that oral feeding of hepatitis B antigens in combination with
allogeneic liver cells to patients with chronic hepatitis leads to a
dose-dependent reduction of anti-HBV antibody titers—an observation
that supports, albeit indirectly, our findings [46]. In fact, we have shown
earlier that oral administration of V1 to normal healthy volunteers does not induce
systemic anti-HIV antibodies [28].These investigations relate to the often ignored
notion of autoimmune nature of AIDS as a disease [42, 43]. If this concept is
correct, then the prevailing AIDS vaccine strategy aimed at activating the
immune response against HIV instead of inducing immune tolerance is flawed. Results
of recent trial of therapeutic AIDS vaccine in which HIV-directed immune activation
was associated with increase in viral load further support this notion [49]. The
observed phenomenon of loss of antibodies against HIV and clinical improvement can
be readily explained by tolerance induction. Due to paucity of guiding
precedents relating to serodeconversion [50–52], the present findings need to
be interpreted cautiously and additional case studies have to be acquired and
analyzed to rule out any possible error.



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