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

12th World AIDS Conference

Abstracts 12109-12113 33

slightly decreased after adjustment. The RH of AIDS for those who seroconverted
for HBV after HIV SC was 3.62 (95%, CI 1.21-10.93 p = 0.02) and was higher
and still significant after adjustment. The RH of death was 6.09 (1.49-24.83 p =
0.01) and was markedly higher and still significant after adjustment.
Conclusion: Individuals who acquired HBV after having seroconverted for HIV
seem to have a more rapid progression to AIDS and death compared with those
who never acquired HBV. No difference was observed between HBsAg-negative
individuals and those who were HBsAg-positive only, or between the former group
and those who were positive for both HBsAg and HBeAg at HIV SC.
12109 Lack of evidence that /3-chemokines are involved in the
control of HIV replication in vivo
Karl-Anton Kreuzer1, J.K. Rockstrom2, B. Kupfer3, U. Spengler4.
1 Wilhelmshavener Strasse 18 10551 Berlin; 2Dpt. of Medicine Univ of Bonn,
Bonn; 3Dpt. of Med. Microbiol & Immunol. Univ of Bonn, Bonn; 4Dpt. of
Medicine Univ. of Bonn, Bonn, FRG
The hypothesis has been proposed that macrophage inflammatory proteins
(MIP)-1 u, MIP-1 / and RANTES may play a significant role in controlling HIV
replication by competitive binding to HIV coreceptors. The aim of the present
study was to investigate whether this possible interaction is reflected by altered
chemokine serum levels with progressive HIV infection. Sixty HIV positive patients, 10 HIV- negative patients with pneumonia and 10 healthy controls were
enrolled into this study. MIP-1 u, MIP-1 ý/ and RANTES serum levels were
detected by enzyme immuno assays and compared to HIV viral load and CD4
counts, 5 '-neopterin and 12-microglobulin as established surrogate markers of
HIV disease progression. While no significant differences were noted with respect
to RANTES serum levels between HIV infected patients (61.1 ~ 32.2 ng/ml),
patients with pneumonia (34.2 ~ 19.6 ng/ml) and normal controls (90.2 ~ 43.9
ng/ml), MIP-1 a and MIP-1 /I were significantly (p < 0.001) higher in HIV negative
patients with pneumonia (MIP-1 a: 28.0 ~ 10.4 pg/ml, MIP- 1 /1: 208.2 ~ 117.3
pg/ml) than in patients with HIV infection (MIP-1 a: 4.3 ~ 10.0 pg/ml, MIP-1 /1:
42.2 ~ 27.3 pg/ml) or normal controls (MIP-1 a: 2.1 ~ 8.9 pg/ml, MIP-1 1: 41.5
~ 76.3 pg/ml). In the HIV infected patients, neither CDC stages nor the surrogate markers of HIV disease progression (viral load, CD4 counts, 5 '-neopterin,
/2-microglobulin) were correlated to any of the chemokines (p > 0.05, r < 0.2).
Although chemokines can be elevated in infectious diseases our data do not
support the concept of altered HIV inhibitory chemokine levels with progressive
HIV infection. As in vitro data indicate at least 100-fold higher chemokine concentrations to be required for inhibiting of HIV replication than those measured in
our study, the chemokines MIP-1 a, MIP-1 t/ and RANTES possibly play only a
minor role in the control of viral burden during HIV disease.
12110 Role of CCR5A32 and CCR2-64i heterozygosities in the
pathogenesis of HIV-1 infection
A. Soriano1, E. Palou1, T. Gallart1, F. Garcia1, J.M. Mir61, J. Alcami2,
A. Cruceta1, J.M. Gatell1. 1Hospital Clinic. University of Barcelona; 2Centro de
Investigacion. Hospital 12 de Octubre. Madrid, Spain
Background: Macrophage (M)-tropic HIV-1 strains use chemokine receptor
CCR-5 and CCR-2 as coreceptors for entry into CD4+ cells. A 32 base-pair
deletion (A32) in CCR5 and a 641 deletion in CCR2 are associated with a slower
rate of progression to AIDS in heterozygotes. To gain insight about the role of
these protective mutant alleles in HIV pathogenesis, the CCR5 and CCR2 genotypes were investigated in a cohort of long-term non-progressors (LTNP) and in
patients with markers of slow progression to AIDS.
Methods: Patients were classified in the following groups: i) 23 LTNP ii) 23
asymptomatic patients (AS) with a documented HIV infection ranging from 6 to 72
months; stable CD4 T cell counts >500 x 106 cells/L, a CD4/CD8 T cell ratio >1
and/or a plasma HIV-1 RNA < 200/ml copies; and iii) 7 rapid progressors (RP):
patients whose CD4+ T cell counts dropped below 350 x 106 cells/L, in a period
<2 years after an acute symptomatic HIV-1 infection. CCR5 and CCR2 genotypes
were analyzed by PCR and single strand conformational polymorphism (SSCP).
Results: Among the 53 patients studied, 12 and 7 were, respectively, heterozygotes for CCR5-D32 and CCR2-641. Neither homozygotes for
CCR5-A32/CCR2-641 nor heterozygotes for both mutant alleles were found. The
frequency of CCR5-A32 heterozygosity in the different groups was 35% (8 of 23)
in LTNP, 13% (3 of 23) in AS, and 14% (1 out of 7) in RP. CCR5-A32 heterozygotes were statistically indistinguishable from those homozygotes for wild-type
(wt) CCR5, with regard to plasma viremia, CD4 and CD8 T cells counts and
CD4/CD8 ratio values. The frequency of CCR2-641 heterozygosity in the different
groups was 4% (1 of 23) in LTNP, 26% (6 of 23) in AS, and 0% (0 of 7) in RP.
No differences existed concerning plasma viremia, CD4 and CD8 T cell counts
and CD4/CD8 ratio values, between the 6 CCR2-641 heterozygotes AS and the
17 wt-CCR2 homozygotes AS.
Conclusions: These results support the evidence of a protective effect of
CCR5-32 heterozygosity against the progression to AIDS. However, our data with
LTNP do not support a role for 641 in postponing progression to AIDS. How
ever, the significantly increased frequency of CCR2-641 heterozygosity among
AS patients with CD4/CD8 ratio >1, suggest it can identify individuals with some
advantageous immunological features.

S12111 HIV patients' survival in Mexico City: The importance of
prophylaxis and antiviral treatment
M. Sigfrido Rangel-Frausto, S. Ponce-de-Leon, A. Villasis Kiever,
G.M. Ruiz-Palacios. Instituto Nacional Nutricion, Vasco de Quiroga 15, TL
Alpan, Mexico, DF, Mexico
Survival and Morbidity of HIV patients has dramatically changed due to the use
of both antivirals and prophylaxis. We retrospectively review our experience with
the management of HIV patients, and specially the impact of therapy in patients'
survival.
We reviewed the charts of patients admitted to the HIV clinic from 1984 to
1995. Three groups could be easily identified according the date of HIV diagnoses: 1984 to 1988 (before the widespread use of antivirals) from 1989 to 1992
(zidovudine and PCP prophylaxis), and from 1992 to 1995 (other antiretrovirals).
We examined 945 charts, 772 (81.6%) progressed to AIDS. The mean survival
time increased from 530 days in the patients from group 1 to 851 en patients in
the group 2 (P < 0.01) and to 1027 days in group 3 (P <.003). We observed over
the different study periods important changes in the frequency of opportunistic
infections or conditions. Pneumocystis carinii pneumonia decreased from 25% in
group 1, to 17% in group 2, and 14% in group 3. Kaposi's sarcoma decreased
from 31% to 10.5 to 13.7% over the same periods (P < 0.001). In contrast, there
was an increase in the diagnoses of Cytomegalovirus infections from 12.5% to
20.5% and 18.5% for the three study periods (P < 0.05), and of waste syndrome
with 36%, 45% and 57% in the same study groups (P < 0.001). In the multivariate
analysis risk factors for mortality were: HIV transfusion associated infection (P =.02) and PCP (P =.007) being the first opportunistic infection, zidovudine and
cotrimoxasol use were associated with a protective effect.
The combined effect of zidovudine and cotrimoxasol in our patients did not
showed a higher protective effect in the survival analysis. Survival of HIV patients
in this historical cohort was clearly associated with the introduction of antiretrovirals, the mechanism of infection, specifically transfusion was associated with the
highest risk of mortality. The introduction of prophylaxis and change in other risk
factors have changed over time the frequency of opportunistic infections.
S12112 Late potentials based on instantaneous heart rate
histogram in HIV positive individuals
Paulo Roberto B: Barbosa1 2, C.A. Morais-de-Sa3, J. Barbosa-Filho3, F.S. Sion3,
J.F.C. Pinto3, J. Nadal4. 1 Rua Mariz e Barros, 775 - 10a Enfermaria - Hosp. Univ.
Gaffree e Guinle - Tijuca - Rio de Janeiro - 20270-004, 2Universidade Do Rio de
Janeiro - Esc. Med Cirurgia, Rio de Janeiro, RJ; 3Hospital Universitario Gaffreee
e Guinle - UNI-Rio, Rio de Janeiro, RJ, Brazil
Objectives: Ventricular late potentials (VLP) are fragmented electrical activities
which originate in regions with delayed conduction in damaged myocardium, and
are markers of ventricular arrythmia due to reentry mechanism. The infection of
myocardial fibers and dendritic cells by HIV and the presence of VLP reinforces
the arrhythmic mechanism underlying the infection. This study was conducted to
assess the prevalence of VLP in HIV positive individuals, and to evaluate whether
VLP shows any influence of the heart rate.
Methods: Fourteen patients (three male), 35 +/- 7 (mean +/- SD) years old,
under clinical follow up in the Gaffree e Guinle University Hospital were admitted
for SAECG evaluation. Five were CDC Class II and 9 were CDC Class IV. Seven
of the CDC Class IV were taking antiviral drugs. The SAECG signals were acquired over 20 minutes with a system previously reported using the XYZ Frank
leads. The histogram of the normal heart rate (IHR) were constructed and the
QRS complexes separated into three classes: modal, pre-modal (higher IHR)
and post-modal (lower IHR). The normal heart beats were all averaged together,
and then separately for each of the instantaneous classes, from which the vector
magnitudes were calculated. The parameters then analyzed were the filtered
QRS complex duration (QRSF), the RMS40 and the LAS40.
Results: Five exams were VLP positive in the ensemble class. When premodal, modal and post-modal classes were considered separately, eight patients
became VLP positive, from five exams in the pre-modal, one in the modal and
six in the post-modal class. Two patients were VLP positive exclusively in the
pre-modal, none in the modal and one in the post-modal class (p = 0.048).
Conclusion: VLP is highly prevalent in the group under study and suggest that
VLP occurrence in HIV positive individuals may be dependent on the instantaneous heart rate, or masked by heart rate variability. VLP may be a useful marker
of myocardial injury in HIV seropositives. This work was partially supported by
the Brazilian Research Council (CNPq) and PRONEX/MCT.
12113 CD4+ lymphocyte counts and HIV disease progression in
subjects co-infected with HIV-1 and HTLV-2
Winston Frederick1, Leleka Doonquah2, R.A. Delepeha2, L.C. Alexis2,
P.L. Sappington2, J.I. McNeil2, W.R.J. Frederick2. 1Howard University Hospital
Suite 5C15 2041 Georgia Avenue NW Washington, DC; 2Howard University
Hospital Washington DC, USA

Background: All reports on retroviral co-infection have been in patients coinfected with HIV-1 and HTLV-1. Several studies suggest that HTLV-1 accelerates
progression of HIV infection. We undertook this study to monitor clinical progression of HIV infection and CD4+ lymphocyte counts in subjects co-infected with
HIV-1 and HTLV-2.
Methods: This is a prospective longitudinal study of subjects co-infected with
HIV-1 and HTLV-2. HIV-1 antibodies were detected by ELISA and confirmed by