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1.  THE AIDS VACCINE QUEST :
India began its first phase 1 human clinical trial
for a preventive AIDS vaccine on February 7,
2005 at the National AIDS Research Institute
(NARI) in Pune. The phase 1 trial in PUne in
testing tgAACO9- the technical name for the
investigational vaccine based on the naturally
occuring adeno associated virus (AAV) ang genes
from HIV subtpye C, tgAACO9 has an AAV capsid
(a protein coat that covers the viral DNA) that is
used to deliver carefully selected genes of HIV
subtype C (gag and pro genes and a portion of
HIV's reverse transcriptase gene).
The rationale of testing tgAACO9 as a preventive
AIDS vaccine candidate is to find out whether it
can prevent the development of AIDS in people
who are not infected with HIV. Preclinical studies
using animal models have been promising,
demonstrating that tgAACO9 is well tolerated
at all dose levels tested. B-cells are while blood
cells of the immune system and produce
antibodies against infections agents. T-Cells
actually destroy cells that carry the infections
agent. Getting and investigational AIDS vaccine
to stimulate both these kinds of cells of the
immune system is one of the biggest challenges
of AIDS vaccine research today. The
manufacturer of the candidate vaccine (using
recombinant DNA techniques) does not utilise
either AAV or HIV. Original AAV genes are
removed from the viru's DNA and replaced with
synthetically copied portions of the HIV genome.
The design of the investigational vaccine is such
that tgAAC09 cannot casue HIV infection or
AIDS.
India is the third country to be part of this
multinational trial. The trail initiation is a great
ABSTRACTS FROM CURRENT LITERATURE
Marfatia Y.S.*, Sharma Archana**
* Professor
** Assistant Professor
Department of Skin & V.D., Medical College and S.S.G Hospital, Vadodara-390 001
Address for Correspondence :
Dr. Y.S. Marfatia, (Professor and Head)
Dept. of Skin & V.D. Government Medical College, Vadodara 390 001 Email : ym11256@yahoo.com
culmination of the triparties partnership among
ICMR, NACO and IAVI.
Subhadra Menon, Sankalp-The News letter of
International AIDS vaccine Initiative (IAVI) in
India.
2.  MORE DATA on HIV IN ORPHARYNX
The infectively of the oral secretions of HIV infected
individuals is thought to be relatively small. Only a
few case reports have described the acquisition of
HIV from oral sex, and although HIV RNA is routinely
found in saliva, it can seldom be cultured, implying
that salivary  factors may neutralize the virus to some
extent. However, the contribution of HIV levels in
oropharyngeal tissue to these findings is still unclear.
Researches explored this issue by swabbing the
tonsilar pillars of HIV infected men who have sex
with men (MSM) for HIV RNA detection and culture.
Forty six of 63 (73 percent) had detectable
pharyngeal HIV RNA. Pharyngeal RNA levels
ranged from approximately 3 log copies / ml to 6 kg
copies/ml. Patients who had undergone tosillectomy
had a lower likelihood of shedding HIV than those
who still had their tonsils (50 percent vs 80 percent).
In a multivariate analysis, use of antiretroviral drugs,
higher CD4 Cell count, and tonsillectomy were all
associated with lower pharyngeal HIV RNA. The
researchers hypoothesize that the tonsils may not
only serve as a repository for cell associated HIV
within their tissue, but may also. with their' rich lectin
glycocalyz surface", provide an accessible site in
the oropharynx where cell-free HIV can survive.
Patients are frequently curious about the likehood
that oral sex an transmit infection. This study
suggests that while doctors should be honest in
saying that these incidents are rare, they should also
mention that the scientific evidence that such
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behaviour is not without risk continues to
accumulate.
Zuckerman RA et al. Factors associated with
oropharyngeal human immunodefiency virus
shedding.
J Infect Dis 2003 Jul 1; 188:142-5.
3. HIGH SEMEN IN HIV LEVELS DURING
ACTUE INFECTION MAY SHAPE
EPIDEMIC
The probability of heterosexual transmission of HIV
per coital act is quite low. Studies have arrived at
rates as low as 1 transmission per 2000 acts, which
if unmodified, would not sustain the current explosive
epidemic in heterosexual AIDS. One possible
explanation for this discrepancy is that men may
have higher levels of virus in semen during actue
HIV infection than during chronic infection.
To evaluate this hypothesis and its implications,
these researchers determined HIV RNA levels in
blood and semen of 30 men a median of 38 days
after estimated date of infection. a model of viral
dynamics suggests that as in levels in the blood,
semen viral RNA levels peak at about 20 days
infection and then subside to set point levels
approximately 1 month later.
The researchers then  created a model of
transmission probaility using these figures. At the
time of peak viremia, they estimate that transmission
probility per coital act ranges from 1 per 1099 acts
for individuals in the 25th percentile of semen viral
levels to 1 per 53 acts for those in the 75th percentile.
Using standard assumptions of coital frequency
these estimates would translate into a range of
probibility of transmission from 0.6 percent to 12.4
percent considerably  higher than similar created
for individuals with chronic HIV infection.
The researchers further extrapolated this data to
suggest than in Africa, where semen viral loads are
higher than those found in this study and where other
sexually transmitted diseases will further enable
transmission, men could infect 50 percent or more
of their female sexual partners during the first 6
weeks of infection.
Pilcher CD et al. Brief but efficient : Actue HIV
infection and the sexual transmission of HIV.
J Infect Dis 2004 May 15; 189:1785-92.
4.  HIV - A HOST GUEST THAT WONT LEAVE
The advent of potent combination antiretroviral
therapy prompted hope that, if treated early, patients
could be cured of HIV infection. That hope
decreased with the discovery years ago that T cells
in patients whose viral loads were successfully
suppressed for up to 3 years on therapy continued
to harbor viable HIV. A recent follow up to the same
subjects after several more years of successful
therapy is no more encouraging.
Limiting dilution subjects of T cells from 62 HIV
infected subjects who had maintained
undertectable viral loads, with only  isolated blips
for upto 7 years yileds 0.03 to 3.00 infectious units
per million resting CD4 cells. The success rate of
viral isolation did not decrease with increasing time
on potent antiretroviral therapy. The half life of HIV
in T cells was 44.2 months. Assuming an average
initial reservoir of 106 HIV infectected T Cells, total
viral eradication would required 73.4 years of
potents therapy. When the analysis was limited to
the 18 individuals with no viral load blips, the
reservoir half life was stili 30.8 months, correlating
with 51.2 years of combination therapy required for
total eradication.
HIV eradication from infected individuals is unlikely
using current antiretroviral regimens and will
probably require novel approaches to address the
prolonged stability of the virus in host T cells. These
data do not, however, preclude long term
suppression of HIV and control of clinical disease
progression as a viable treatment strategy.
Siliciano JD et al. Long term follow up studies
confirm the stability of the latent reservoir for HIV 1
in resting CD4 (+) Tells.
Nat Med 2003 Jun; 9:727-8.
5. SHORt Cycling to maintain immunity
In one recent piolt study of 10 patients strict
adherence to short cycle structured intermittent
therapy (SIT) involving twice daily PI based therapy
was associated with HIV suppression and stable
CD4 cell counts, Now, the same group has reported
a study of eight antiretroviral experienced pateitns
with HIV suppression who short cycled one daily
NNRTI based therapy.
Seven participants repeated short off on cycles 7
days without ART, followed by 7 days of once daily
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ddI + 3TC + Efavirenz - for 60 to 84 weeks; one
dropped out for personal reasons at week 24. All
participants maintained HIV RNA levels < 50 copies
/ ml. at each measurement without viral "Bilips" >50
copies / ml. while they remained on the study
schedule. None showed significant CD4 cell count
changes, evidenced of antiretroviral resistance, or
serious adverse drug effects.
For patients who can adhere to such a regime short
cycle SIT might suppress HIV replication while
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reducing therapy cost and cumulative antiretroviral
exposure. This approach, if proven safe and
efficacious could offer hope for HIV infected
individuals in resource limited settings.
Dybul M et al. A proof of concept study of short
cyle intermittent antirectroviral therapy with a once
daily regiment of didanosine, lamivudine and
efavirenz for the treatmet of chronic HIV infection.
J infect DIs 2004 Jun 1; 189-1974-82.
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