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

XIV International AIDS Conference

Abstracts ThPeB7182-ThPeB7186 383

ThPeB7182 Absence of detectable viremia in semen of
HIV-infected patients treated with effective
efavirenz-containing antiretroviral regimen
G. Liuzzi, M. Zaccarelli, A. Amendola, P. Sette, S. Topino, G. D'Offizi, G. Ippolito,
M. Capobianchi, P. Narciso, C.F. Perno, A. Antinori. National Institute for
Infectious Diseases "L. Spallanzani", INMI L. Spallanzani via Portuense 292,
00149, Roma, Italy
Background: The efficacy of sexual transmission of HIV-1 primarily depends on
the concentration of infectious virus in semen. In order to evaluate the effectiveness of a NNRTI-based antiretroviral regimen in reducing HIV-1 viral load in male
seminal fluid, we quantified HIV-1 RNA in semen of HIV-infected patients in treatment with a combination regimen including two nucleoside reverse transcriptase
inhibitors and efavirenz.
Methods: Paired plasma and semen specimens were collected after informed consent from patients consecutively attending our outpatient clinic between September and November 2001 and currently treated with an efavirenzcontaining HAART regimen. HIV-1 RNA was performed on the samples using
branched-DNA method with a lower detection limit of 50 copies per ml. A control
group of antiretroviral nafve patients was also analyzed.
Results: Overall, 22 efavirenz-treated and 6 naive patients were included. Considering efavirenz-treated patients, 18 (81.8%) and 20 (90.2%) patients had
plasma and semen viral load <50 c/ml, respectively. Semen HIV-1 RNA resulted
<50 c/ml in all patients with undetectable and in two with detectable plasma level
(Kappa statistics 0.621; P=0.026). HIV-1 RNA level in semen was found >50 c/ml
in two patients, but both were lower than 3.0 log10 c/ml. By contrast, none of the
six nalve patients showed undetectable HIV-1 RNA level in plasma and only two
of six (33.3%) in semen.
Conclusions: Efavirenz-containing antiretroviral regimens can greatly reduce
HIV viral load in semen of sexually active male individuals. Undetectable or low
level of HIV replication are also found in patients with active replication in plasma.
Our findings suggest that the seminal fluid of efavirenz-treated patients with HIV-1
viremia under control may be considered at low risk of transmitting HIV.
Presenting author: Andrea Antinori, INMI L. Spallanzani, via Portuense 292,
149, Roma, Italy, Tel.: [phone], Fax: [phone], E-mail: antinori
@inmi.it
ThPeB7183 Duration of treatment and reasons for changing in
a cohort of patients in Brazil
E. Sprinz, C. Rech, G. Marafon, S. Kelbert, R.A. Zimerman, R.P. Santos. HCPA -
Federal University of Rio Grande do Sul, Rua Desembargador Moreno Loureiro
Lima 385/601, RS, 90.450-130, Brazil
Background: Higly active antiretroviral treatment (HAART) dramatically changed
the history of AIDS, but changes due to intolerance or failure are common. The
study analysis rate and causes for treatment discontinuation in a population in
south of Brazil.
Population & Methods: In a cohort of 1,421 individuals, 664 patients which
started HAART (had to had exposure to no more than 3 nucleoside analogues)
were selected. First, a general analysis was conducted; after, three standard
"state-of-the-art" regimens (ZDV or d4T+3TC+ indinavir (IDV), n=128, or nelfinavir (NFV), n=87; or efavirenz (EFZ), (n=89) were analysed for discontinuation
(ritonavir boosted regimens were excluded).
Results: Overall, 66% (n=438), changed treatment in 12 months: 35% due to intolerance, 26% due to disease progression, 24% due to incomplete viral supression - IVS (plasma viral load > 1.000/mm3), and 9% due to medical advice. When
comparing "state-of-the-art" regimens, 65% (n=83) in IDV arm stopped treatment
in a median of 13 months: 63% due to intolerance or adherence problems, progression of disease in 17%, and IVS in 11%. The median duration in NFV arm was
17 months (48%): intolerance (29%), progression of disease (24%), IVS (21%),
and medical advice (14%) were the reasons. In EFZ arm 16% (n=14) changed
treatment at 13 months. The reasons were intolerance (64%), progression of disease (19%), and 3% adherence problems. Regimens with EFZ were statistically
more durable whem compared with IDV and NFV; relative risk (RR) with IDV was
4,12 (CI 2,51-6,78, p <0,0001); RR of discontinuation of NFV was 3,07 (CI 1,81 -5,20,p<0,0001) comparing with EFZ. The RR of changing indinavir compared to
nelfinavir was 1,34 (IC 1,04-1,73,p=0,02).
Conclusion: HIV therapy is still troublesome with more than 60% changing in one
year and the main reason for discontinuation were drug intolerance/adherence.
Regimens with EFZ were more durable when compared with IDV and NFV in real
life.
Presenting author: Eduardo Sprinz, Rua Desembargador Moreno Loureiro Lima
385/601, RS, 90.450-130, Brazil, Tel.: +55 - 5133301618, Fax: +55 - 5133301618,
E-mail: [email protected]

ThPeB7184I Effects of 5 year suppression of HIV on T cell
co-stimulation: Implications for long term immune
recovery
C. Tsoukas, J. Cox, L. Gilbert, J. Szabo, G. Hatzakis. Montreal General Hospital,
Montreal General Hospital, 1650 Cedar Ave. Room A5-140, Montreal, Quebec
H3G 1A4, Canada
Background: HIV not only causes CD4 cell depletion, it also down-regulates

expression of the co-stimulatory molecule CD28 on T cells. Co-stimulation is necessary for optimal T cell activation and is delivered jointly with the T cell receptor
signal. In the absence of appropriate co-stimulation, anergy is induced: T cells
fail to proliferate and respond to specific antigens. Potent antiretroviral therapy
causes partial short-term reversal of this process. We therefore undertook a 5
yr study to monitor specific immune phenotypes associated with co-stimulation
and activation, including CD28 expression, in the context of long term treatment
success or failure.
Methods: Immune phenotypes were evaluated by 3 color FACS analyses. A multivariate model was used to predict virologic outcomes of a prospectively followed
cohort of 1008 patients undergoing antiretroviral therapy (ART). 10,046 observations were generated during a mean follow-up of 48-17 months. Successful therapy, Group A (n=361 pts) was defined as having <500 copies/ml HIV RNA consecutively for over 6 months. Treatment failure, Group B (n=647 pts) consisted of
individuals who maintained >1,000 copies of HIV RNA. Variables analyzed: percent and absolute values of CD4, CD8, CD38, HLA-DR, CD28, CD4/CD8 ratio,
lymphocytes, length of treatment. Kaplan-Meier was used for risk assessment.
Results: the following variables remained in the model:
Group A Group B
Factors Adjusted-R P-Value Factors Adjusted-R P-Value
CD8/HLA-DR% 0.186 <0.0001 Lymphocytes -0.244 <0.001
CD8% 0.128 <0.0001 CD8/CD28+% -0.178 <0.001
CD4% -0.083 0.001 CD4/CD8 -0.166 <0.001
CD38% 0.095 <0.001 CD8/CD38% 0.165 <0.001
Length of treatment 0.078 0.002 Length of treatment 0.131 <0.001
CD8/CD28+% 0.046 0.206 CD3% -0.103 <0.001
Conclusions: A decrease in CD28+CD8+ cells was strongly correlated with treatment failure. Normalization trends in CD28 expression were noted with successful
treatment, however they were not statistically significant in the long term.
Presenting author: Chris Tsoukas, Montreal General Hospital, 1650 Cedar Ave.
Room A5-140, Montreal, Quebec H3G 1A4, Canada, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
ThPeB7185 Effect of STI on HIV rebound and CD4-mediated cell
functions
D. Goletti, D. Vincenti, S. Carrara, C. Montesano, S. Topino, C. Agrati, F. Poccia,
S. Carrara. IRCCS L.Spallanzani, Roma, Italy
Structured therapy interruption (STI) may boost anti-HIV specific immunity acting as an autologous live vaccine. Nevertheless, STI may present the potential
risks of HIV-mediated loss of CD4+ cells and severe constitutional symptoms. We
evaluated the effect of STI on the CD4-mediated immune function in chronically
HIV-1 infected asymptomatic patients with undetectable HIV-RNA plasma during
at least two years. A clinical and immunological follow-up was performed at the
suspension of HAART (TO), after 1 month from the suspension (T1), at the resumption (T2), and after 30 days from HAART-resumption (T3). Twelve patients
were studied in terms of modulation of CD4 cell number and percentage (naive,
long term memory and effector phenotype) and HIV-load. Immune response to
mitogen, HIV protein (p24), recall antigen were studied overtime in terms of cell
proliferation and IFNg production, both evaluated at day 7 post culture in thawed
cells. The results show a statistically significant decrease of CD4 cell number
during the period of therapy interruption (TO vs T1, p=0.004) that correlated with
viral rebound. After HAART resumption CD4 cells increase to the levels of preSTI (TO vs T4 p>0.05). Immune response to mitogen (PHA) decreased at T1
and T2, although it was not statistically significant. In addition at T3, 5 out of
9 showed an increase of the mitogenic response. No HIV-specific immune response was observed at TO; however at T3 in 2 out of 8 patients an induction of
HIV-specific response was found. At T1 and T2 a loss of CMV-specific immune
response was shown with a recover in 5 out of 7 patients studied. During STI no
clinical symptoms were observed in the patients analyzed. In conclusion although
STI causes a CD4 cell loss and although this effect correlates with a decrease
of CD4-mediated cell function during the interruption period, an increase of mitogenic response, an induction of HIV-specific and CMV immune response was
found after therapy resumption.
Presenting author: Delia Goletti, Via Portuense 292. Roma 00149., Italy, Tel.:
[phone], Fax: [phone], E-mail: [email protected]
ThPeB71 86 Prevalence of transient detectable viral loads
("blips") in a clinical population of HIV infected
patients maximally suppressed on antiretroviral
therapy
M. McSweeney1, C. Vaamonde2, B. Boyle2. 1CSS, 525 east 68th street, new

york, ny, 10021, United States; 2CSS/New York Presbyterian Hospital, New York,
United States
Background: Patients on ART with HIV RNA viral loads (VL) consistently below the level of quantification (BLQ, <400 or <50 c/mL) can occasionally have a
detectable VL determination among many that remain BLQ. The significance of
these VL "blips" is unclear, with little clinical data available to date.
Methods: Retrospective study of all patients (Pts) followed at a clinic in New York