Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

458 Abstracts ThPeC7484-ThPeC7488

XIV International AIDS Conference

ThPeC7484 The impact of highly active antiretroviral therapy
(HAART) on cancer incidence in the Multicenter
AIDS Cohort Study (MACS).
E.C. Seabergi1, L. Kingsley2, S. Melnick3, Z.F. Zhang4, H. Armenian1,
J.S. Chmiel5, J. Roe6, L.P. Jacobson1. 'Johns Hopkins University, JHU -
Bloomberg School of Public Health, Department of Epidemiology, 615 North
Wolfe Street, Room E-7011, Baltimore, MD 21205, United States; 2University of
Pittsburgh, Pittsburgh, Pennsylvania, United States; 3National Cancer Institute /
NIH, Bethesda, Maryland, United States; 4University of California at Los
Angeles, Los Angeles, California, United States; 5Northwestern University
Chicago, Illinois, United States; 6National Institute of Allergy and Infectious
Diseases /NIH, Bethesda, Maryland, United States
Background: The widespread use of highly active antiretroviral therapy (HAART)
has reduced the incidence of AIDS-defining malignancies. However, it remains
unclear whether HAART impacts the incidence of other cancers.
Methods: Cancer incidence between 1/1990 and 12/2000 was investigated using data from 2236 HIV-infected men enrolled in the MACS. Outcomes were confirmed malignancies. Follow-up time was partitioned into two calendar periods,
1990-1995 and 1996-2000, to represent the pre-HAART and HAART eras, respectively. Age and race adjusted standardized incidence ratios (SIR) were computed using US male population data. To assess the impact of HAART on cancer
incidence, SIRs for the two periods were compared using exact methods for Poisson data.
Results: The incidence of Kaposi's Sarcoma (KS) and non-Hodgkin's lymphoma (NHL) were significantly (p<.001) elevated during both time periods,
KS: SIR=287.1 (90-95) and 75.7 (96-00); NHL: SIR=83.3 (90-95) and 27.8 (96 -00). In each case, the SIR declined significantly (p<.001) over time. The combined incidence of all non-AIDS-defining malignancies (NADM) was significantly
(p<.001) elevated during 90-95 (SIR=3.2), but not during 96-00 (SIR=1.1). This
decline was also significant (p=.002). The NADMs with significantly (p<.05) elevated SIRs during 90-95 were buccal cavity/pharynx (SIR=7.0), anus (SIR=48.6),
testes (SIR=4.0), liver (SIR=16.9), and multiple myeloma (SIR=27.7). These SIRs
dropped to non-significant levels during 96-00, but no individual decline was statistically significant, possibly due to small numbers.
Conclusions: The introduction of HAART produced a significant decline in the incidence of AIDS-defining malignancies, although the incidence of these cancers
among HIV-infected men remains significantly higher than in the general population. Simultaneously, the incidence of combined NADMs has declined significantly
to an adjusted rate comparable to that in the general population.
Presenting author: Eric Seaberg, JHU - Bloomberg School of Public Health,
Department of Epidemiology, 615 North Wolfe Street, Room E-7011, Baltimore,
MD 21205, United States, Tel.: [phone], Fax: [phone], E-mail: [email protected]
ThPeC7485 Falling incidence of AIDS related Kaposi's sarcoma
on HAART. The protective effect of NNRTI's
S. Portsmouth, M. Bower, S. Mandalia, M. Nelson, B.G. Gazzard. Chelsea and
Westminster Hospital, 27 Ingestre Court, Ingestre Place, London, WIF OJL,
United Kingdom
Objective. To determine the incidence of Kaposi's sarcoma (KS) in HIV-1 infected
individuals since the introduction of Highly Active Antiretroviral Therapy (HAART)
in 1996.
Methods. From the database of 8640 patients followed up at the Chelsea and
Westminster Hospital since 1985, all cases of KS were identified. Using Univariate Log linear regression modeling, the rate ratio of KS incidence was calculated.
Evidence of virological or immunological treatment failure was sought from the
case notes of those with KS. Nadir CD4 cell counts were identified for both pre
1996 and post 1996 KS patients (The nadir CD4 count was the lowest CD4 count
recorded in the database).
Results. From the total cohort of 8640 patients' 1204 cases of KS were identified.
198 cases of KS were diagnosed between 1996 and 2001. The incidence of KS
was constant at about 30 cases per thousand patient years before 1995. In 1995
and 1996 the incidence was 7.6 per thousand patient years - co-incident with dual
therapy, and since 1996 the incidence has fallen dramatically to 0.03 per thousand patient years in 2001. Of the 198 cases of KS diagnosed since 1996 only
35 patients were on HAART at the time of diagnosis and of these 30 were highly
antiretroviral experienced (mean 6.6 regimens) and were experiencing treatment
failure. The median nadir CD4 count in the pre-HAART era and in the post-HAART
era of those developing KS was similar, 44 cells/mm3 (interquartile range 13-125)
and 78 cells/mm3 (interquartile range 14-213) respectively. The incidence of KS
was significantly lower in patients on regimens containing NNRTI's compared with
Pl's.
Conclusion. Since the introduction of HAART in 1996 the incidence of Kaposi's
sarcoma has dropped sharply. Most Kaposi's sarcoma occurs in antiretroviral
nalve patients. Patients developing KS whilst on HAART are usually experiencing
treatment failure. NNRTI's are equally as effective at preventing KS as Pl's.

Presenting author: Simon Portsmouth, 27 Ingestre Court, Ingestre Place, London, W1F OJL, United Kingdom, Tel.: [phone], E-mail: simonportsmouth
@ hotmail.com

ThPeC7486I AIDS-Associated Cervical Cancer in Europe and
USA, 1994-2000
S.H. Ebrahim', M.T. McKenna1, R. Selik', FF. Hamers2. 1CDC, Mail Stop E-46,
CDC, 1600 Clifton Road, Atlanta, GA 30345, United States; 2European Centre
for Epidemiologic Monitoring of AIDS, St Maurice, France
Background: Cervical cancer incidence has been on the decline in developed
countries.
Objective/Methods: To assess the trends and determinants of invasive cervical
cancer (CCA) among women with AIDS in Europe and the United States (USA),
we analyzed the AIDS surveillance data from Europe (reported by 18 countries
of the WHO-European region) and the USA (excluding cases meeting only immunological criteria), among women aged 15 years or older, 1994 through 2000
(N=Europe 17,757, USA 36,509).
Results: Overall, from 1994 through 2000, the annual incidence of women with
AIDS declined (Europe, 3418 to 1274; USA, 7064 to 3456) and the percentage of
women with AIDS who had CCA as the initial AIDS-defining condition decreased
(Europe 3.0% to 2.2%, p=0.509; USA 2.8% to 1.6%, p=0.001). By 1999, nonHodgkin Lymphoma, which was stable as a proportion of cases, replaced CCA
as the most common malignancy among women with AIDS. For the majority of
women who had AIDS-associated CCA, CCA was the only initial AIDS-defining
condition (Europe, 90% [435/484]; USA, 88% [666/761]). From 1994 to 2000,
among intravenous drug users, there was no significant variation in the percentage of women with CCA (overall average, Europe 3.5%, USA 2.3%), whereas the
percentage of all women with AIDS who acquired HIV through intravenous drug
use declined (Europe 57.0% to 36.4%, USA 43.0% to 26.7% [p<0.001]). Among
heterosexuals, CCA decreased (Europe 2.5% to 1.9%, p=0.466; USA 2.6 to 1.6,
p=0.0372).
Conclusions: Trends in cervical cancer among heterosexual women with AIDS
in Europe and USA follow those in the general population. The non-declining
trends in CCA among intravenous drug users calls for targeted cervical cancer
prevention interventions.
Presenting author: Shahul Ebrahim, Mail Stop E-46, CDC, 1600 Clifton Road,
Atlanta, GA 30345, United States, Tel.: [phone], Fax: [phone],
E-mail: [email protected]
ThPeC7487 Expression of Human Herpesvirus 8 (HHV-8) K1
suppresses apoptosis of BJAB cells induced by
anti-fas antibody
F. Samaniego. MD Anderson Cancer Center, Box 429, Department of
Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX 77030, United
States
Background: Human herpesvirus 8 (HHV-8) is associated with the development
of primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS).
Virtually all PEL contain HHV-8. K1 is expressed in HHV-8 infected individuals
and PEL-derived cell lines express K1 during lytic phase viral replication.
K1 encodes for a transmembrane protein containing a short cytosolic tail with
an immunoreceptor tyrosine-based activation motif (ITAM). K1 has been shown
to aggregated and potentially interact with other membrane receptors. K1 induces activation of NF-kB and its expression in animal models has produced
lymphomas. Given its NF-kB induction properties, we anticipated that k1 induces
transformation in part by suppression of apoptosis.
Methods: To study the role of HHV8 K1 gene product, we generated K1 stably
expressing cell line BJAB-K1 and vector alone cell line BJAB-XS.
Anti-Fas antibody was used to stimulate apoptosis and cells were monitored
for membrane protein Annexin-V and morphological changes of apoptosis. (1)
The K1 expression stable cell lines BJAB-K1 and empty vector cell line BJABXS were established by the transfection of plasmids pLXSN-K1 and pLXSN. (2)
Apoptosis of BJAB-K1 and BJAB-XS cells was induced by anti-Fas antibody. (3)
Apoptosis rates of cell lines were compared with Annexin-V-FITC/PI analysis and
DAPI-based nuclear morphological analysis. (4) Data were analyzed by PairedSamples T test.
Results: (1) The stable cell lines BJAB-K1 and BJAB-XS were confirmed by
PCR-based detection of K1 and vector DNA; (2) Fas mediated apoptosis was
suppressed in BJAB-K1 cells versus BJAB-XS in Annexin-V assa); and (3) apoptosis in BJAB-K1 was also suppressed when analyzed by DAPI staining.
Conclusion: Our data indicates that the expression of HHV8 K1 can suppress
Fas mediated apoptosis. The results suggest that K1 participates the pathological process through the prevention of apoptosis.
Presenting author: Felipe Samaniego, Box 429, Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX 77030, United
States, Tel.: [phone], Fax: [phone], E-mail: [email protected]

ThPeC7488 Anal PAP smears in HIV+ patients at a community
based clinic
S.M. Fine, J.J Castiglia, R.B. Corales, M.L. Christie, K.M. Mang, C.R. Sellers,
W.M. Valenti. Community Health Network, Community Health Network, 758
South Avenue, Rochester, New York 14620, United States
Issues: The incidence of human papilloma virus (HPV) induced anal/rectal disease is higher in HIV infected persons than in the general population. Screening