Final Program and Oral Abstracts [International Conference on AIDS (8th: 1992: Amsterdam, Netherlands)]

THURSDAY, 23 JULY 1992

ThB 1548-ThB 1549

ThB 1548 RISK FACTORS FOR THE DEVELOPMENT
OF ACYCLOVIR-RESISTANT HERPES SIMPLEX VIRUS (HSV) INFECTION.
Safrin. Sharon; Elbaggari A.; Elbeik T. San Francisco General Hospital, University of
California San Francisco CA 94110 USA.
Obiectives: We performed a case-control study to determine the risk factors associated with the development of
acyclovir-resistant HSV infection in HIV-infected patients.
Methods: The Research Virology Laboratory at San Francisco General Hospital has served as a reference laboratory
for testing of antiviral susceptibility to HSV since 1988. Resistance to acyclovir is defined as IDA>3 ug/ml by the
plaque reduction assay; acyclovir-susceptible and -resistant control isolates are run with each test. Clinical
information was requested from the referring physician regarding the following: location of lesion, length of time
present, HSV type if known, response to antiherpes agents, first known outbreak of HSV, CD4 count, peripheral
white blood cell count, and albumin level. Patients who were not HIV-infected were excluded. Univariate analyses
were performed using the Wilcoxon rank-sum test; multivariate analyses used logistic regression.
Results: We studied 47 HIV-infected persons with in vitro resistance to acyclovir; "controls" were comprised of
23 HIV-infected persons in whom testing demonstrated susceptibility to acyclovir. Resistance to acyclovir in vitro
was associated with the following variables by univariate analysis: absolute CD4 count (p=.02), duration of lesion
at the time of referral for testing (p=.0001), lesion size (p=.05), absolute lymphocyte count (p-.03), days of
acyclovir treatmst for the acute episode (p=.01), and estimated weeks of lifetime acyclovir usage (p=.01).
Multivariate analysis demonstrated that only absolute CD4 count (p=.02) and duration of the lesion (p=.03) were
independently associated with in vitro resistance to acyclovir. Absolute CD4 count, absolute lymphocyte count, and
serum albumin were highly intercorrelated (p-.002), and HSV type was highly associated with location of the
lesion (p=.0001).
Conclusions: Chronicity of mucocutaneous HSV infection and level of HIV-associated immunosuppression are the
strongest risk factors for the development of resistance to acyclovir in vitro. Treatment of HIV-infected patients with
CD4 < 100/mm' must include administration of adequate dosages of acyclovir until healing is complete.
Sharon Safrin M.D. San Francisco General Hospital
Bldg 80, wd 84. 995 Potrero San Francisco CA 94110
telephone (415) 206-5948 telefax: (415) 206-5981
NOTES

ThB 1549 HIV-1 REVERSE TRANSCRIPTASE MUTATIONS IN CHILDREN TREATED WITH
ZIDOVUDINE. Principi N*,Vago T**,Massironi E*,Tornaghi R*,De
Papquale MP**,Picco P* and Marchisio,Paola*. *Pediatr Dept 4,
University of Milan,**Endocrine uniTOspeale Sacco,Milan,ltaly
Objective To evaluate the presence of HIV-1 mutations in HIV infected children
treated with zidovudine (ZDV)
Methods 19 HIV infected children (9 P2A,4 P2AB,2 P2AC,1 P2AD1,3 P2AF) treated
with ZDV (600 mg/m2/day) were prospectively followed-up monthly with clinical and
laboratory controls. The presence of mutant HIV-1 strains was determined by
analyzing with PCR the codon 215 of the reverse transcriptase gene of the DNA
derived from PMBC. Clinical outcome was defined as stable or deteriorating.
Results Children were treated for a median of 18 mo. (range 2 - 36). No child
demonstrated mutant HIV-1 strains before starting ZDV. 10/13 children who
received more than 6 months of ZDV were demonstrated to have mutant strains. The
percentage of mutant strains over wild strains ranged from 15 to 100%.
Deterioration of clinical condition was demonstrated in 8/10 children who had
mutant HIV-1 strains while all children in whom no mutations were found the
clinical condition remained stable over time (p<0.01). The clinical evolution was
worst in children who has the highest proportion of mutans strains.
Conclusions These data indicate that spontaneous HIV-1 mutations are probably
rare and that ZDV therapy is strongly associated with their emergence.Moreover,
the presence of mutants is associated with a higher risk of progression of HIV
disease. Children in monotherapy with ZDV should be monitored for the possible
emergence of mutant HIV-1 strains.
Marchisio,Paola; Pediatric Department 4,University of Milan
Ospedale L.Sacco - Via GB Grassi 74 - 20157 MILAN, ITALY
phone [phone] fax [phone]

NOTES

NOTES

NOTES

Th75