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

626 Abstracts 33170-33174

12th World AIDS Conference

F33170 ] The thiocarboxanilide UC-781 is a potential virucidal drug
Jan Balzarini1, E. Verbeken2, M. Laga3, L. Van Damme3, L. Van Mellaert1,
J. Anne1, E. De Clerq1. 1Rega Institue for Medical Research, Minderbroersstraat
10. B-3000 Leuven; 2Department of Pathology I, University Hospital St. Rafael
B-3000 Leuven; 3Institute for Tropical Medicine, Department of Microbiology
B-2000, Antwerp, Belgium
Introduction: The non-nucleoside reverse transcriptase (RT) inhibitor (NNRTI)
UC-781, synthesized by Uniroyal Chemical Ltd. (Guelph, Ontario, Canada) belongs to the structural class of thiocarboxanilide derivatives. It is a highly potent
and selective HIV-1 inhibitor in cell cultures and displays a favorable sensitivity/resistance spectrum (Balzarini et al., Mol. Pharmacol. 50: 394-401, 1996).
UC-781 has also recently been shown to possess virucidal properties (Borkow et
al., J. Virol. 81: 3023-3030, 1997).
Results and Discussion: UC-781 has been formulated in a lipophilic preparation (replens). This formulation was remarkably stable upon prolonged exposure
(up to 30 days) to relatively high temperatures (i.e. 50 C). When UC-781, formulated as 0.5%, 0.2% and 0.05% replens gel, was exposed to HIV-1-infected CEM
cell cultures, it protected the CEM cells against HIV-1 -induced cytopathicity. This
points to an efficient diffusion of UC-781 from the gel to the medium. Subsequent
subcultivations resulted in virus breakthrough at the 0.05% replens gel formulation, but not at higher (0.2%, 0.5%) concentrations. The virus that emerged in
the presence of 0.05% UC-781 replens gel did not show NNRTI-characteristic
resistance mutations in its RT, and retained full sensitivity to UC-781 and other
NNRTIs. UC-781 also proved stable at lower pH (i.e. pH 3.5), suggesting it may
also be stable in the vaginal environment. UC-781 did not show systemic side
effects, nor local inflammation or disruption of the vaginal mucosa when intravaginally exposed to rabbits for 10 consecutive days as 10% UC-781 in replens
gel. Under these conditions, levels of UC-781 as low as 20 ng/ml could not be
detected in the plasma of drug-treated animals. Also, UC-781 did not affect the
growth of vaginal commensals such as Candida and Lactobacillus strains.
Conclusion: The favorable physical (pH and temperature stability, and easy
formulation in replens gel), toxicological (no measurable local side effects in
the rabbit vagina) and virological (high potency, favorable resistance spectrum)
properties make the thiocarboxanilide UC-781 a promising drug candidate to be
further investigated as a vaginal microbicide.
246*/ 33171 Tolerability of antiretroviral agents used by
health-care workers (HCWs) as postexposure
prophylaxis (PEP) for occupational exposures to
HIV
Adelisa Panlilio, D.M. Cardo, S. Campbell, P. Srivastava. Nash Surveillance
Group; CDC Mailstop E-68 Atlanta Georgia 30333, USA
Background: In June 1996, the US Public Health Service recommended the use
of combinations of antiretroviral agents (ARVs) as PEP following certain occupational HIV exposures. Except for zidovudine (ZDV), there is little information on
the tolerability of ARVs in persons not infected with HIV.
Methods: Data collected on occupational exposures to HIV and reported to the
National Surveillance System for Hospital Health Care Workers were analyzed to
assess the tolerability of ARVs used as PEP.
Results: From June 1995 through December 1997, 188 HCWs reported occupational exposures to HIV. Of the 114 HCWs for whom at least one follow-up
was available, 58 took PEP, 53 did not, and 3 had missing PEP information. Of
the 58 HCWs who took PEP, 16 (28%) took ZDV alone; 20 (34%), ZDV and
one other ARV; 20 (34%), a combination of three ARVs; and two (4%), four
ARVs. Nineteen HCWs completed their PEP regimens as prescribed, 21 stopped
prematurely, four modified their regimens, and 14 had missing information. Of
the 21 HCWs who stopped their PEP prematurely, 16 (76%) did so because of
symptoms; three (14%), due to HCW choice; and two (10%), for other reasons.
Forty-one (71%) of 58 HCWs taking PEP reported one or more symptoms. The
most commonly reported symptoms were nausea, reported by 24% of HCWs;
fatigue or malaise, 22%; emotional distress, 13%; headache, 9%; and loss of
appetite, 6%. While HCWs not taking PEP also reported symptoms, they reported
them less frequently, with symptoms being reported by 13 of 53 not taking PEP
vs. 41 of 58 (relative risk 2.88, and 95% confidence interval 1.75-4.75) taking
PEP.
Conclusion: A large proportion of HCWs taking PEP experienced at least one
symptom while on PEP. This often was the reason for discontinuation of PEP.
Counseling of HCWs about potential side effects of PEP along with symptomatic
treatment may help ensure compliance with PEP regimens.
249*/33172 Post-exposure prevention (PEP) following high
risk sexual or injection drug use: A model
feasibility program
James O. Kahn. San Francisco PEP Project, University of California, San
Francisco, CA; University of California, San Francisco, SPGH 995 Potrero, San
Francisco, CA 94110, United States

Background: PEP may reduce HIV incidence following occupational exposure.
This study was initiated to evaluate the feasibility and consequences of PEP
following high risk sexual or injection drug use exposures. Primary goals were
to determine the characteristics of persons presenting for PEP; ascertain the
proportion of persons who elect anti-retroviral therapy; identify source partners;
determine the ability to comply with anti-HIV drugs; evaluate the safety of the

medications; offer risk reduction counseling to high-risk individuals; and examine
the subsequent behavior of study participants.
Methods: Educational outreach to community-based organizations and a 24
hour hot line were established. Persons reporting unprotected sexual activity or
needle sharing are seen within 72 hours of the exposure and are provided HIV
testing and counseling as well as offered 4 weeks of combination anti-retroviral
therapy. Subjects may decline treatment. Baseline demographics and risk factors
are assessed and laboratory studies are performed (including detection of other
STDs). Follow-up includes risk reduction counseling.
Results: As of 1/26/98 we enrolled 66 participants (55 men and 11 women). 49
are Caucasian; 5 Latino/Hispanic; 3 Asian; 3 Pacific Islander; 3 African American
and 3 of other ethnicities. The rate of enrollment averages one per day and the
median time since exposure was 57 hours. Thus far, no one has tested positive
for HIV at baseline. Primary exposure routes that led to PEP participation were:
35 receptive anal intercourse; 14 anal insertive; 8 vaginal receptive; 5 vaginal
insertive; 4 oral receptive with ejaculation; and 3 injection drug equipment sharing. 105 source partners were identified: 26 known to be HIV+; 33 of unknown
HIV status; 3 sex workers; 40 anonymous male partners; and 3 exposed by
injection drug equipment. 61 subjects accepted medication and 5 refused. Two
subjects have repeated PEP for a subsequent HIV exposure and 4 were lost to
follow-up; 8 subjects experienced some treatment associated toxicity and discontinued treatment; one subject has become infected with HIV during the 4 weeks
of treatment.
Persons seeking PEP following high risk behavior can be identified within 72
hours of exposure. A variety of exposures lead people to seek PEP. Most persons
accept treatment when it is provided. To date, medications are well tolerated and
follow-up has been excellent. The rate of sexually transmitted diseases among
those who present for PEP will be determined. Thus far, one subject has become
HIV infected; analysis of the viral genotype as well as the subject's medication
adherence will be presented.
33173 Characteristics of individuals presenting for
post-exposure prophylaxis (PEP) following high risk
sexual exposure: Opportunities for counseling
Jeffrey N. Martin1, M.E. Roland2, J.O. Kahn2, J. Bamberger2, M.H. Katz2,
M.A. Chesney2, T.J. Coates2. 1UCSF Center for AIDS Prevention Studies 74
New Montgomery, San Fran., CA 94105; 2University of California San Franciscp
San Francisco CA, USA
Background: The suggested efficacy of PEP with anti-retrovirals following occupational exposure has prompted debate over PEP following sexual or drug use
exposure. If PEP for these exposures is made available, it is unknown what types
of individuals will access it. If PEP availability brings forth a chronically high-risk
population, the post-exposure encounter will provide an important opportunity to
access these individuals.
Methods: A descriptive study of the feasibility and consequences of PEP following sexual or drug use exposure was started in San Francisco. Persons with
reported unprotected sexual (receptive or insertive anal or vaginal intercourse; or
receptive oral intercourse with ejaculation) or drug use exposure within the past
72 hours to sources with either known or suspected HIV infection are offered
HIV testing, counseling, and 4 weeks of combination anti-retroviral therapy. Prior
3-month sexual behavior was assessed by structured interview.
Results: Detailed sexual behavior characteristics are available on the initial 37
participants: 25 men who have sex with men (MSM), 3 heterosexual men, 1 man
who refused to report orientation, 7 women and 1 transgender. Median number
of sexual partners in the prior 3 months was 5 for MSM (range 1 to 30; 28% had
10 or greater), 3 for heterosexual men (range 2 to 5), and 2 for women (range
1 to 7). In MSM, while the median number of partners (including the partner for
the presenting event) with whom participants practiced unprotected sex was 0
for receptive oral sex and 1 for receptive anal sex, 4 of 25 (16%) MSM had
2 or more partners with whom they practiced unprotected oral sex. All of the
heterosexual men and one of the women had 2 or more partners with whom they
had unprotected vaginal sex in the prior 3 months.
Conclusions: Most MSM seeking PEP had many partners in the prior 3 months,
but, except for the presenting event, generally had safe practices. In addition to
the potential benefit offered by medications, the post-exposure encounter for them
is an opportunity for counseling reinforcement of safe behavior. Some MSM and
women, however, and all of the limited number of heterosexual men seen to date
had chronically high-risk practices. The PEP encounter is a valuable opportunity
to access and provide intensive counseling to this high-risk group.
1 250* / 33174 Post-sexual exposure prophylaxis (PSEP) with
HAART after sexual assault
George Opio, R. Torres, R. Alvalle. St. Vincents Hospital and Medical Center,
412 Sixth Avenue Suite#401, New York, NY 10011, USA
Introduction: The known efficacy of HIV prophylaxis with HAART after occupational exposure raises the issue of HIV post sexual prophylaxis (PSEP) following

sexual assault, although the risk of acquiring the infection is not known. Cases
of HIV seroconversion following rape have been reported and perpetrators often
have several risk factors for HIV.
Methods: Following a documented case of HIV seroconversion after a rape of
a female survivor treated with AZT/3TC/Saquinavir for 4 weeks at our Institution,
a protocol for the provision of HIV prophylaxis using HAART to sexual assault survivors, was initiated in July 1997. Criteria for offering HAART for PSEP included