Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 33155-33159 623

33155 Carrageenan based formulations for preventing infection
by enveloped viruses
David Phillips, R.A. Maguire, V.R. Zacharopoulos. Population Council, 1230 York
Ave, New York, NY, USA
Background: Evidence suggests that Nonoxynol-9 (N9) and the sulfated polysaccharides carrageenan may be effective as active ingredients in topical microbicides. We compared vaginal formulations of carrageenan with and without N9 with
OTC spermicides for efficacy in protecting mice from infection following vaginal
inoculation with herpes simplex virus 2 (HSV-2).
Methods: Test formulations were 1) 2% carrageenan + 1% carbopol, 2) 3%
carrageenan, 3) 2% carrageenan + 1% carbopol + 2% N9, 4) 3% carrageenan +
2% N9, 5) Gynol II' and 6) K-Y PLUS". All formulations had approximately the
same viscosity. Formulations were placed in the vagina of progestin treated mice
5 min prior to inoculation with HSV-2. Infection was determined by the presence
of inflammation and lesions in the genital region.
Results: Formulations of carrageenan significantly protected mice from infection following vaginal inoculation with HSV-2. OTC spermicides tested were
slightly less effective. Formulations of carrageenan + N9 were significantly more
effective than OTC spermicides containing the same amount of N9. Carrageenan
formulations with 2% N9 were as effective as OTC products in killing spermatozoa
as accessed by the Sander Cramer test. Carrageenan formulations are stable as
ageing at 40 C for 1 month did not effect viscosity or efficacy against HSV-2 or
spermicidal action.
Conclusion: Formulations of carrageenan may be effective in blocking infection by HSV-2 without affecting fertility. Carrageenan based N9 spermicides
may be more efficacious than existing glycerol based formulations in preventing
infection by herpes simplex virus and possibly other enveloped viruses.
33156 Genital transmission of SIVmac251 in cynomolgus
Macaques as an animal model to evaluate vaginal
microbicide
Carol Tevi-Benissan1, A. Nandeuil2, M. Makuwa1, G. Dubreuil1, H. Berard2,
L. Belec3. Centre International de Recherches Medicales BP 769 Franceville
(CIRMF), Gabon; 2 Laboratoires Innothera, Arcueil; 3Lab Virologie Hopital
Broussais, Paris, France
Objective: To optimize the size of the genital inoculum of SIVmac251 in
Macaques, to finally evaluate the efficiency of benzalkonium chloride (BZC)
to prevent vaginal transmission of SIV.
Methods: During the luteal phase of the menstrual cycle (22 days after the
start of menstruation), 4 females Cynomolgus Macaques recieved vaginally 18.9
mg of BZC just prior to the inoculation of 4000 AID50 cell-free SIVmac251, diluted
in PBS containing 50% of human seminal plasma; another group of 4 female
macaques used as controls received the same dose of placebo (= excipient) prior
to inoculation. Clinical, virological (SIV culture, PCR detection), and immunological (seroconversion) follow-ups of inoculated animals were carried out at days 7,
14, 21, 28, 45, 60 and 90 post-inoculation.
Results: In the group of females receiving BZC, no contamination was observed (negativity of all virological and immunological markers). In the control
group, 2 animals presented clinical manifestations resembling acute SIV infection
(enlargement of spleen and lymphe nodes); both animals seroconverted at days
21 and 45, respectively, while at day 90, the serum anti-SIV antibodies became
undetectable; in all controls, viral cultures in PBMC cocultured with CEMx174 and
in plasma remained negative.
Conclusion: The dose of SIVmac251 initially used for inoculation did not appear sufficiently high to induce persistent infection, since two animals belonging
to the control group were not infected while the remainings presented a transient
infection. These preliminary results underline the need to rigourously control all
parameters of SIV vaginal transmission, including the dose of inoculum, to conclude on the possible effect of BZC to prevent the sexual transmission of SIV in
the Macaque model.
33157 Using condoms or microbicides for the first three months
of a relationship only may prevent spread of HIV among
European and Caucasian heterosexuals
Knut M. Wittkowski. NY ACAD Med-Ctr Urban EPID Studies 1216 5th Ave, New
York, NY 10029, USA
Objectives: Many heterosexuals fail to use barrier methods, because they consider it impractical to practice safer sex indefinitely (or until the partner is tested).
A strategy only requiring use of barrier-methods for a limited period of time is
likely to be more acceptable. Including spermicides into the prevention message
targeted towards heterosexuals is likely to further improve compliance.
Methods: Heterosexual spread of HIV is modeled under the following assumptions: The reproduction number is less than 1.5. Heterosexuals engaged in
a sexual relationship have the majority of their contacts within the relationship
and are less promiscuous than singles. Heterosexuals who never engage in

long-term relationships are most likely to import HIV. Sexual activity is highest
early in a relationship where risk factors in the partner's history are still unknown.
Infectivity is high during the "window-period", where antibody tests are still negative. Thereafter, infectivity remains low until the first symptoms appear. At this
time, both sexual activity and promiscuity are low because of decreasing sexual
attractiveness and disease-related changes in life-style.

Results: Compliance is more important than method effectiveness. High compliance during the initial period of relationships is more important than an average
compliance throughout the relationship. This effect is due to an interaction between several factors. (1) Short-term relationships with partners of unknown
risk-factors are protected. (2) The "window period" and the period of "high sexual
activity" are protected. (3) Infections within a long-term relationship are less likely
to cause additional infections due to "saturation" within the relationship.
Conclusions: If most heterosexuals would use condoms or microbicides during
the first three months of a relationship (including contacts outside the relationship) the reproduction number due to vaginal transmission among heterosexuals
would be less than 0.5, i.e. on the average, every imported infection would cause
only one additional infection (including all secondary, tertiary, etc. infections),
thus the impact of the HIV epidemic on the heterosexual population would be
limited.
[1] (1988/89) AIFO 3: 401/4: 3; (1989/95) AIDS 3: 143/9: 310: (1995/96) Gesundh-Wes 57:
291/58: 229; (1998) AJPH (in press)
33158 BufferGel: Results of the first phase I study of a novel
vaginal microbicide
Kenneth Mayer1, J. Peipert1, T. Fleming2, S. Cu-Uvin1, S. Horton2, T. Moench3,
Z. Rozenberg4. IBrown University AIDS Program, Providence, RI; 2University of
Washington, Seattle, WA; 3ReProtest LLC, Baltimore, MD; 4Division of
AIDS/NIAID, Bethesda, MD, USA
Objectives: To evaluate the safety and tolerability of BufferGel (ReProtect LLC:
IND #49,744), a negatively charged, non-absorbable high molecular weight polymer gel, designed to maintain vaginal pH below 5 in the presence of semen.
Design: A Phase I study was designed which initially screened 38 low risk
abstinent or sexually-active monogamous women in Rhode Island who consented
to a pelvic exam. 11 were not enrolled because of baseline infection, mucosal
disruption, or lack of willingness to participate once they learned what the protocol
entailed.
Methods: Participants underwent baseline colposcopy at baseline and after
14 days of product use once a day, with a speculum exam on day 7. Participants
with no abnormalities at day 14 then used the product twice a day, with the same
clinical evaluation protocol. Primary safety/toxicity endpoints were: systemic toxicities or mucosal ulceration, abrasion, severe erythema and/or edema. They also
were interviewed to assess acceptability.
Results: 16 sexually abstinent and 11 monogamous women used the product
once or twice a day. Male partners were instructed to always use condoms. No
serious adverse events (AE) were seen; 18 participants reported AE's, with all
but 4 noting mild symptoms. Only one AE was probably/possibly drug-related.
AE's tended to be superficial and self-limited; the most common symptom was
vaginal pruritus. There was no evidence to suggest that AE's correlated with dose
frequency. After initiation of product use, 3 women were withdrawn; two developed vaginal candidiasis, one developed a hyperkeratotic lesion. Median baseline
vaginal pH was 4.6, and on product was 4.5 or less in 93% of 82 determinations:
the median pH decrease from baseline levels was 0.55 after 7 days, and 0.30
after 14 days, with once daily product use. Acceptability questionnaires, diaries,
and focus groups suggested a high level of willingness to use the product if it
were available.
Conclusions: The rationale for the use of BufferGel as a microbicide is its
ability to maintain a low pH which inhibits HIV replication. BufferGel appears to be
non-toxic and well-tolerated by low risk US women, and capable of maintaining a
low vaginal pH, used either once or twice daily. Further studies of BufferGel are
currently underway overseas.
S33159 HIV/STD prevention, topical microbicides and rectal sex
Clark Taylor. 10 Corwin St. #5, San Francisco, CA, USA
Issue: Because unprotected receptive anal sex is potentially such a tremendous
risk for HIV/STD infection, rectal microbicide research is urgent. To achieve this
goal, research issues must be clarified and addressed when different from vaginal
microbicide development.
Project: To identify problems specific to rectal microbicide research, biomedical rectal and vaginal data were compared and issues pertinent to vaginal
microbicides were studied. Anecdotal reports were gathered from professional
sexologists and sexually active women and men. Also, medical researchers on
microbicides were consulted.
Results: The rectum and vagina differ greatly in structure, function, surface
area, tonicity, acidity, flora, fauna, and contents. These differences raise special
problems for rectal microbicide development. Examples are: a) how much product is needed to adequately coat the intestine; b) do feces affect efficacy; c) is
defecation necessary before inserting a product; d) will a product dissolve feces,
cause diarrhea or constipation; e) will a product be easily retained during sex, f)
can it be and should it be voided after sex; g) can gas be passed without product
expulsion; h) does rectal absorption affect efficacy and safety; i) can the same
microbicide be used for both vaginal and rectal sex; j) is the length of time a

particular microbicide remains active the same or different for the rectum and
vagina. These questions must be addressed: for when a product is eventually
approved for vaginal use, it will be adopted by many for anal sex and vice versa,
regardless of instructions or label warnings. Unfortunately, formulas which are
safe, effective and appealing for vaginal sex may be harmful, useless and/or
obnoxious in the rectum.