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

12th World AIDS Conference

Abstracts 22310-22314 325

regardless previous cytology. HPV typification may help on finding the better
follow-up for each case.
22310 Local HIV-1 expression in the female genital tract
following treatment of cervical intraepithelial neoplasia
Tedd Ellerbrock', T.C. Wright2, S. Subbarao', J.L. Lennox3, C.E. Hart1.
1 Centers for Disease Control (CDC) 1600 Clifton Road E45 Atlanta Ga 30333;
2Columbia University New York NY; 3Emory University Atlanta GA, USA
Objectives: We have previously shown that, after treatment of cervical intraepithelial neoplasia (CIN), HIV-1 RNA levels increase 1.0-3.6 logs in vaginal secretions,
while plasma levels remain relatively constant. The objective of this study is to
determine if the source of the increased HIV-1 RNA in vaginal secretions following
treatment of CIN is blood or local expression.
Methods: Plasma and vaginal lavage samples were obtained from four women
during an exam 2 weeks after treatment of CIN. The C2-V3 region of gp120
in HIV-1 was analyzed by direct cycle sequencing of DNA, which was amplified from reverse-transcribed RNA. Phylogenetic analysis was performed with a
neighbor-joining tree, using 100 bootstrap replications. To estimate the proportion
of viral load in vaginal lavages that was derived from HIV-1 RNA in blood, the
amount of blood in vaginal lavages was measured, using a quantitative assay for
hemoglobin.
Results: The nucleotide differences between plasma and vaginal HIV-1 from
the four women were 0.9%, 1.7%, 5.8%, and 6.0% with predicted amino acid
differences of 0.2%, 0.8%, 11.2%, and 14.8%, respectively. These differences
indicate that two of the four women had a major species of HIV-1 in vaginal
lavage that was significantly different from the major species in plasma. External contamination was excluded by phylogenetic analysis, which showed a >99
bootstrap value between plasma and vaginal HIV-1 of each woman. Less than
0.1% of vaginal HIV-1 was derived from contaminating blood, and thus, blood
could not account for the close similarity of major species in two of the women.
Conclusion: These results show that HIV in vaginal secretions can be derived
from local expression, and locally expressed HIV can have significant genotypic
differences from plasma virus. These findings may have important implications
for the development of vaccines to prevent heterosexual and perinatal HIV transmission.
624*/22311 Comparison of the amount of HPV 16 DNA in
cervicovaginal secretions of HIV-infected and
-uninfected women, using quantitative
competitive-polymerase chain reaction (QC-PCR)
Thomas Wright1, X.W. Sun', T.V. Ellerbrock2, M.A. Chiasson3. 'Columbia
University Dept of Pathology Room 16-428 630 St NY; 2Centers For Disease
Control, Atlanta, GA; 3New York City Department of Health, New York, USA
Objectives: Previously, we have shown that HPV 16, the HPV type most often associated with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer,
is more prevalent and more persistent in cervicovaginal secretions of HIV-infected
women without CIN. The objective of this study was to determine if the amount of
HPV DNA 16 in cervicovaginal secretions is increased in HIV-infected women.
Methods: Study participants were selected from women enrolled in a prospective cohort study that was begun in 1991. Each woman underwent colposcopy, as
well as biopsy when indicated, and HPV DNA testing of a cervicovaginal lavage
(CVL), using PCR and E6 type-specific primers for HPV 16. CVLs containing HPV
16 DNA were analyzed to determine the amount of HPV 16 DNA, using QC-PCR.
Results: A convenience sample of 52, including 30 HIV-infected and 22 uninfected, women with CVLs containing HPV 16 DNA was selected. Of the 52, a total
of 21 (40%), including 16 (53%) HIV-infected and 5 (23%) uninfected, women
had CIN. The geometric mean amounts of HPV 16 DNA in CVLs were 0.199 and
0.044 fg/103 cells for HIV-infected and uninfected women (p < 0.001); 0.160 and
0.080 fg/103 cells for women with and without CIN (p = 0.09); and 0.269 and
0.141 fg/103 cells for HIV-infected women with and without CIN, respectively (p
= 0.23). In a multiple regression analysis that controlled for CIN, HIV infection
remained significantly associated with an increased amount of HPV 16 DNA in
CVLs (p < 0.003).
Conclusion: In women infected with HPV 16 who have not developed CIN,
the amount of HPV 16 DNA in CVLs is significantly increased in those who are
HIV-infected. Alterations in the amount of HPV shed into the lower anogenital tract
may explain in part why HIV-infected women are at increased risk of developing
CIN.
22312 |Early regression of cervical lesions in HIV-seropositive
women receiving highly active antiretroviral treatments
(HAART)
Isabelle Heard1, V. Schmitz2, D. Costagloila3, G. Orth4, M.D. Kazatchkine1
SINSERM U430 Hp. Broussais, Paris; 2lnst. Pasteur, Paris; 3INSERM SC4
Paris; 4INSERM SC4, Paris, France

Background: Severe immunodeficiency in HIV disease is associated with a high
prevalence of high grade cervical squamous intraepithelial lesions (SIL) and of
oncogenic HPV genotypes in the cervix. We investigated whether HAART has
any effect on the natural history of SIL in HIV+ women.
Methods: A triple combination antiretroviral therapy including a protease inhibitor was started in 85 women with advanced HIV disease. Cytologic test and

colposcopic examination together with detection of HPV DNA in cervical smears
by PCR and Southern blotting were performed prior to HAART and after 5 months
of HAART.
Results: The prevalence of SIL decreased from 66% to 49% after a median
duration of 5 months of HAART. Partial regression to lower grade of SIL was observed in 7/20 women who initially presented with high grade SIL; total regression
to normality was observed in 1 women who initially presented with high grade SIL
and in 16 women who initially presented with low grade SI. At both examinations,
the prevalence of HPV infection was 60% by Southern Blot and high risk HPV
genotypes were identified. There was a trend toward a higher increase in CD4
cell counts in the regression subgroup of patients
Conclusion: Our observations indicate that HAART does not result in clearance of HPV-infected cells but reduces the clinical expression of HPV disease in
some HIV+ women.
22313 Relationship between HIV viral load, CD4 level and
cervicovaginal human papillomavirus infection in HIV+
women
Joel Palefsky, H.M. Minkoff2, L.A.K. Kalish3, A.M.L. Levine4, S.M. Melnick5,
P.M. Miotti6, R.D.B. Burk7. 1 University of California, Box 0100, San Francisco,
CA 94143; 2SUNY Health Science Ctr. Brooklyn, Brooklyn, NY; 3New England
Research Inst., Inc., Watertown, MA; USC School of Medicine, Los Angeles,
CA; 5National Cancer Inst., NIH, Bethesda, MD; 6Nat. Inst. of AIDS Infect.
Disease, NIH, Bethesda, MD; 7Albert Einstein College of Medicine, Bronx, NY,
USA
Objectives: No studies have yet reported the association between human papillomavirus (HPV) infection and HIV viral load in HIV+ women. The aim of this
study was to characterize the relationship between CD4 level, HIV viral load and
cervicovaginal HPV infection in a large cohort of HIV+ women.
Methods: 1778 HIV+ women participating in the Women's Interagency HIV
Study were tested at baseline for HPV DNA using a cervicovaginal lavage specimen. HPV testing was performed using 30 cycles of polymerase chain reaction
with HPV L1 consensus primers and probes. Each specimen was also tested for
the presence of /I-globin DNA as a positive control. HIV viral load was measured
using the NASBA assay.
Results: 1483 HIV+ women had evaluable baseline HPV, CD4 and HIV viral
load data. The results are shown in Table 1. Both lower CD4 levels (p for trend
<.001) and higher HIV viral loads (p for trend <.001) were associated with HPV,
but the presence of both trends depended on the level of the other factor.
Table 1. HPV prevalence in HIV+ women, stratified by HIV viral load and CD4 level (cells/mm3)
HIV viral load CD4 < 200 CD4 200-499 CD4 -500
(copies/ml) N+/Total N % N+/Total N % N/4Total N %
<4,000 (undetectable) 29/37 78% 132/225 59% 101/230 44%
4,000-20,000 40/48 83% 64/116 55% 40/81 49%
>20,000-100,000 95/122 78% 124/185 67% 42/66 64%
>100,000 173/242 71% 66/103 64% 20/28 7490
*The lowest HPV prevalence cells are not shaded and higher HPV pervalence cells are denoted
with increasing shading.
Conclusions: Cervicovaginal HPV infection is common among HIV+ women at
all levels of HIV viral load and CD4 count. The prevalence of HPV was highest at
CD4 counts <200 cells/mm3, regardless of HIV viral load, but was also uniformly
high at a HIV viral load of >100,000 copies/mi. These data suggest that at their
extremes, both factors may be important in activation of HPV replication and
facilitation of subsequent HPV detection.
22314 Prevalence and follow-up of anogenital oncogenic human
papillomavirus (HPV) infections in a cohort of 121
HIV-positive men
Christine Drobacheff1, J.M. Voltz1, C. Derancourt1, S. Counes-Marquet2,
C. Mougin2, R. Laurent1. 1Dermatologie 2-CHR St. Jacques-25030 Besancon,
Cedex; 2 Virologie-CHR St. Jacques, Besancon, France
Objective: A high prevalence of anogenital oncogenic HPV infections is reported
in HIV-positive patients. This propective study was undertaken to determine the
prevalence, the clinical and histological characteristics, the type and the evolution
of the HPV lesions in HIV-positive men.
Methods: 121 HIV-positive men were included from May 1995 to May 1997:
84/121 (69.4%) homo-bisexual men, 16/121 (13.2%) heterosexual men, 19/121
(15.7%) IV drug users. All the patients underwent anogenital examination with the
colposcope, before and after application of 5% acetic acid solution, and an anuscopy in case of perianal lesions. Biopsies were taken from some of the subjects
with lesions for histological examination. The in situ hybridization technique using
three biotinylated probes which detect HPV 6/11, 16/18, 31/35/51 was applied for
HPV typing. A clinical follow-up was made every 1 to 3 months.
Results: 19/121 (15.7%) patients had HPV infection: genital lesions in 7/19

(36.8%), anal lesions in 7/19 (36.8%), and anogenital lesions in 5/19 (26.4%)
of the patients. In 9/19 (47%) of the cases, histological examination showed an
intra-epithelial neoplasia: PIN I (1), PIN II (2), PIN III (2), AIN II (3) and one
anal carcinoma. One other patient had an invasive anal carcinoma two years
before. The HPV types 6/11, 16/18 and 31/33/35 were positive in 9/17 (53%),
6/17 (35.3%) and 6/17 (35.3%) biopsies respectively. The evolution of the clinical lesions was: recovering in 9/19 (47.3%) of the patients, recurrence in 3/19