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

12th World AIDS Conference

Abstracts 60686-60690 1127

expression and cytokine production in chronically HIV-1-infected promonocytic
U1 cells and acutely infected human monocytes.
Design and Methods: U1 cells stimulated with PMA, TNF-u, IL-6 or IL-10
were coincubated with I,-MSH [1-13] or [11-13] (10 4 to 10 17 M) for 48 h.
Percoll-separated normal monocytes were acutely infected with HIVBAL (MOI =
10 5) in the presence or absence of ac-MSH [11-13] 10 5M. The peptide was
added to cultures daily or 3 times/wk for 3 weeks. HIV expression was evaluated by measuring p24 antigen release and reverse transcriptase (RT) activity.
Cytokine production was estimated using commercial ELISA methods and membrane bound TNF-oy expression by flow-cytometry. NF-kB activity was estimated
by EMSA, and TNF-Oi mRNA by Northern blotting.
Results: both --MSH [1-31] and [11-13] reduced HIV expression in PMA- or
cytokine-stimulated U1 cells but the tripeptide was much more potent than the
parent molecule. The tripetide inhibited NF-kB expression in U1 cells stimulated
with TNF-o. TNF-ao mRNA expression was slightly reduced by cV-MSH [11-13]
whereas there was no change in TNF-a protein production and in membrane
bound TNF-xu. (Y-MSH [11-13] likewise decreased RT activity in acutely-infected
human monocytes.
Conclusion: o,-MSH peptides inhibited HIV expression in infected monocytes,
at least in part through inhibition of NF-kB and TNF-a expression. These molecules
are safe and inexpensive and might be used as an adjunctive therapy together
with antiretroviral agents to treat HIV infection.
60686 Nitric oxide synthesis during acute SIVmac251 infection
of Macaques
Donatienne Blond, A. Cheret, H. Raoul, P. Caufour, F. Theodoro, R. Le Grand,
D. Dormont. CEA, DSV DRM, SNV, IPSC, CRSSA 60-68 Avenue, De La Div.
Leclerl Fontenay/Roses BP6, France
Background: Nitric oxide (NO') is a highly reactive nitrogen intermediate which
mediates numerous physiological functions, including the vasodilation glutamate-induced neurotoxicity, cytotoxicity of activated macrophages and antiproliferative T cells activities. This molecule is synthetized in macrophages by inducible
Nitric Oxide synthase (iNOs) and could contribute to the modulation of the immune
response during HIV-1 infection. In order to study the interactions between the
NO* synthesis and HIV-1 infection in vivo, we examinated, the expression of iNOs
mRNA in mononuclear cells from bronchoalveolar lavage (BALMC) and, the NO*
production in plasma, during acute SIVmac251 infection of macaques.
Methods: BALMC and plasma were obtained during acute infection from two
macaques intravenously inoculated with a pathogenic isolate of SIVmac251. The
kinetics of hematological, virological and immunological changes were determined
simultaneously. NO* production was measured by Griess reaction. Quantification
of IFNy and iNOs gene expression was realised by RT-PCR. BAL were performed
before infection and at days 0, 7, 14, 21, 31 p.i.
Results: The monkeys became infected and seroconverted between the third
and the fourth week p.i.. Infectious cell-free viruses were detected in the serum
of the two monkeys two weeks p.i. In the same way, p27 antigen values peaked
between days 14 p.i. and 17 p.i. and then became undetectable by day 28 p.i.
Analysis of NO* production in plasma of these two monkeys has shown large
amounts of nitrate secretion 14 p.i. INOs gene expression by BALMCs was observed as soon as the second week of infection, and increased until day 31 p.i.
This overexpression was correlated with a marked linear IFNy mRNA expression
increase in BALMCs.
Conclusions: The impact of NO* production on SIV infection is difficult to predict. However, the iNOs gene expression associated with overexpression of IFNy
mRNA in BALMCs as well as the increase of NO* production in plasma during
acute lentiviral infection was observed in absence of opportunistic infections. This
might contribute to HIV-1 associated organ dysfunction and immunosupression
by damaging heatlthy tissues widely invided by HIV-1 infected macrophages, and
the inactivation of lymphocytes.
60687 Sexuality in the era of HIV/AIDS in Zambia:
Socio-economic factors, cultural practices and emerging
behaviours
Jacob Record S. Malungo. Australian National University Canberra, Australia
Background: Zambia lies along the AIDS-BELT stretching from the Central
African Republic and Southern Sweden through Uganda, Rwanda, Burundi,
Kenya, Tanzania and Malawi then southwards to Zambia, Zimbabwe, Botswana
and Namibia and some parts of South Africa and Switzerland which accounts
for more than four-fifths of the current HIV infections in the region. In 1994, the
sero-positive rate in the country was estimated at 28 percent in the urban areas
and 13 for the rural areas with 400 to 500 people said to be infected with the virus
daily.
Methods: This study was based on a cross sectional data including 1996
Zambia demographic and health survey.
Results: It has been discovered that the factors behind the high risks of infection
in this region in general and Zambia in particular are socio-economic and cultural

in nature; the more educated people. The urban dwellers, those in polygynous
unions and the poverty-stricken have higher risks of contracting HIV. The study
also noted that sexual-behaviour in Zambia is the greatest challenge in combating
HIV/AIDS. While the study discovered that polygyny is widespread in the country,
with incidences whereby women with two or more co-wives not uncommon, it was
also found that some two percent of married women and 7% of unmarried women
had two or more sexual partners. On the other hand, 14% of the married men and

more than one-fifth of the unmarried men respectively had two or more sexual
partners. The practice of sexual-cleansing and/or widow-inheritance observed in
the study area are also additional risk factors to the spread of HIV.
Some recent changes in sexual behaviour in the form of resorting to temporary
sexual inactive, maintenance of virginity, restriction to one sexual partners and
increased use of condoms, among others, however have also been witnessed.
Other than the diverse consequences, aspects of especially peer-counselling
HIV/AIDS awareness and campaign programmes and the sensitisation of inheritance laws, augmenting safe-sex, improved home-based-care system, and
involvement of all stake holders (in particular the NGOs, CBOs, traditional rulers
and church organisations) in the fight against HIV/AIDS are some of the possible
preventive and control mechanisms discussed in the paper.
S60688 Methodological issues in socio-sexual investigation of
men having sex with men in Finland
Olli Stalstr6m, J.P. Lemtonen, K.H. Huotari. Hietaniemenkatu 5. Finnish HIV
Foundation, Helsinki, Finland
The english project sigma (socio-sexual investigation of gay men and AIDS) was
started in 1986 as a longitudinal study of a non-clinic-based cohort of homosexuality active men. Respondents were recruited by a variety of means including
response to a postal questionnaire in the gay press, recruitment in gay pubs,
clubs and social and political organisations, in-depth interview schedules and
sexual diaries. A comparative study of sexual practices was carried out in 1992
by the (then) EC-concerted action on AIDS/HIV in 8 European countries.
The questionnaires, interview schedules and sexual diary forms have been
translated into finnish and the study has been replicated in Finland by the finnish
HIV foundation. The sigma research methods were adapted to the finnish circumstances with some changes. Autobiographies were added as a new method. By
January 15, 1998 a total of 643 core questionnaires, 56 in-depth interviews, 31
sexual diaries and 21 sexual autobiographies have been obtained.
We will report in how the international study was applied in Finland and how
the problems in sampling in a Sparsely-populated country were overcome.
60689 | HIV-1 Vpr mediated immunosuppression in vitro
Velpanoi Ayyavoo1, Sagar Kudchodkar1, Artin Mahboubi2,
Maaalingan Sundrasamy1, J.P. Reddy1, D.B. Weiner1. 'University of
Pennsylvania Philadelphia, 505 Stellar-Chance Labs.. 422 Curie Blvd.,
Philadelphia, PA; 2Lojolla Institute of Immunology 2A, San Diego CA, USA
HIV-1 Vpr gene encodes for 14 KDa protein that has been implicated in influencing viral pathogenesis in vitro through interactions with host cell factors.
When we investigated the effects of Vpr on host cell activation, we observed that
Vpr influenced cellular proliferation, and importantly, it modulated TCR triggered
apoptosis. In the absence of TCR mediated activation Vpr induces apoptosis
and in the presence of TCR ligation, Vpr abrogates the expected induction of
the apoptotic pathway. The regulation of apoptosis was found to be due to the
ability of Vpr to suppress NF-kB activity through the induction of IkB transcription.
Interestingly, the expression and release of cytokines and chemokines, which are
NF-kB dependent, were also suppressed by Vpr. One of the consequences of this
interactions includes modulation of immune activation in vitro. We have observed
that Vpr specifically modulates the immunologically important Cell surface and
activation molecules involved in immune activation both in vitro and in vivo. In
addition to this, viral replication kinetics in Vpr treated cells by both macrophage
and T tropic viruses showed significant increase (3 fold) when compared to control
cells.
These observations support the assertion that Vpr is playing a role in compromising the immune system in vitro by modulating the host cellular transcription as
it relates to immune signaling and aiding the virus to evade host immune defense.
S60690 Host factors responsible for differences in HIV-1
susceptibility
Hetty Blaak1, L. Ran2, H. Schuitemaker2. 1Plesmanlaan 125, 1066 CX,
Amsterdam; 2CLB Sanquin Blood Supply Foundation, Amsterdam, Netherlands
Objectives: In a previous study we compared 10 monogamous homosexual
couples between whom HIV-1 transmission had occurred with 10 monogamous
homosexual couples with a discordant HIV-1 serostatus despite high risk sexual
behaviour. We were able to show that the HIV-1 susceptibility of the cells of the
(non-) recipient together with the infectious cellular HIV-1 load in their respective
HIV-1 infected partners were important risk factors for transmission. Differences
in HIV-1 susceptibility correlated in part with the CCR5 genotype. In agreement,
reduced susceptibility was restricted to NSI HIV-1 variants.
Methods: We studied whether differences in susceptibility correlated with
CCR5 and CD4 expression levels, beta-chemokine production, IL-2 production
and cell proliferative capacity in response to PHA stimulation. This study was
performed with peripheral blood mononuclear cells from healthy blood donor

volunteers with a known CCR5 genotype.
Results: We observed a reduced number of CCR5 positive cells and a reduced CCR5 cell surface expression in individuals with a CCR5 A32 heterozygous
genotype. However, CCR5 cell surface expression did not correlate with HIV-1
susceptibility. We also did not observe a correlation between beta-chemokine
production levels and HIV-1 susceptibility. CCR5 is predominantly expressed
on memory (CD45RO) T cells while naive (CD45RA) T cells express predom