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

12th World AIDS Conference

Abstracts 12188-12192 49

12188 Can durable viral suppression in patients with primary
HIV infection using HAART lead to HIV eradication?
Li Ean Goh1, L. Perrin3, D. Cooper4, C. Tsoukas5, B. Hoen6, H. Gaines7,
S. Kinloch2. 1GlaxoWellcome Research and Development, Greenford Rd,
Greenford Middlesxe, Ubgohe; 2Royal Free Hospital, London, UK; 3Hopital
Cantonal, Geneva, Switzerland; 4St. Vincent's Hospital Medical Centre, Sydney,
Australia; 5Montreal General Hospital, Montreal, Canada; 6Hospital
Saint-Jacques, Besancon, France; 7Swedish Institute for Infectious, Stockholm,
Sweden
Background: Efficacy of antiviral treatment is dependent on the time of treatment
initiation and the potency of the antiviral regimen. By treating patients early in the
course of the acute HIV-1 infection with a potent quadruple antiviral regimen it
might be possible to reduce the length of antiviral treatment and to preserve HIV-1
specific immune functions which might be operative in preventing resurgence of
viremia after stopping treatment.
Methods: 100 patients at the early phase of acute HIV-1 infection (<3
positive bands on Western blot) will be treated with a four drug regimen
(AZT/3TC/abacavir/amprenavir) in an international study (Europe, Australia,
Canada) for a first period of 36 weeks. At 36 weeks those patients with viremia
lower than 50 HIV-1 RNA copies/ml will be randomised to continue quadruple
therapy or to switch to a triple therapy regimen including AZT/3TC/abacavir for
at least 15 months. The second phase of the study will compare whether a
scaled down induction maintenance regimen, by improving compliance, is more
efficacious than quadruple therapy. Frequent monitoring will be performed for
virological and immunological parameters in peripheral blood and "sanctuary
sites"; lymph nodes, mucosal tissue, genital secretions and CSF. The aim is to
assess with the most sensitive methods available directly (virological parameters)
or indirectly (immunological parameters) the decline of viral load and eventually
disappearance of all indicators of viral production. This will provide the opportunity
to interrupt antiviral treatment in selected patients under careful monitoring.
This study aims at the evaluation of the concept of eradication in a very
favourable clinical setting combining early intervention at the beginning of acute
HIV-1 infection with the use of a potent antiviral regime. Close monitoring of
virological and immunological parameters will be used to monitor decline of viral
load and the dynamics of immunological parameters including responses towards
HIV.
12189 Human CD8+ T-cell differentiation in acute viral and
chronic HIV-1 infection: Persistently expanded memory
populations
Maryke Th. L. Roos1, R.A.W. van Lier1, D. Hamann', L. Dekker', J.M.A. Lange2,
F. Miedema3, P.T.A. Schellekens4. Clin. Viro-lmmunology, C.L.B., Plesmanlaan
125, 1066 CX, Amsterdam; 2NATEC/Div. Infect. Diseases, AMC, Amsterdam;
3Clin. Viro-lmmunology, C.L.B./Human Retrovir, AMC, Amsterdam; 4Clin.
Viro-lmmunology C.L.B./Dept. Int. Medic., AMC, Amsterdam, Netherlands
Objectives: In response to viral infections unprimed naive CD8+, MHC class
I-restricted, virus-specific T cells clonally expand and differentiate into memoryand effector-type cells. Although several cell-surface markers can be used to distinguish the above mentioned subpopulations (Hamann et al, JEM 1997), details
of human CD8+ T-cell differentiation in response to viral infections in vivo are
largely unknown.
Methods: We studied changes in CD8+ subset distribution in 11 subjects with
acute viral infection, including HIV-1, EBV and CMV, and in 44 subjects with
chronic HIV-1 infection using combinations of CD45RA, CD27 and CD28 mAb.
Results: In acute viral infection a more than 10-fold expansion of CD8+ T
cells with a memory-type CD45RA CD27+ phenotype was observed. These cells
had a high expression of Ki-67, a cell cycle specific nuclear antigen. Numbers of CD45RA+CD27 CD28 effector-type cells with high perforin and low
Ki-67 expression substantially increased after infection. Strikingly, an intermediate CD45RA CD27'CD28 subset emerged that appeared to have moderate
perforin expression but modest Ki-67 expression. After the acute stage of HIV-1
infection, CD45RA CD27+ memory-cell numbers declined sharply, but remained
high, while the number of all other subpopulations were comparable to those during the acute stage of the infection. At the final stage of HIV-1 infection, despite
the decline in number, naive CD45RA+CD27~ cells had a remarkably increased
percentage of Ki-67+ cells.
Conclusion: Our data show that the dynamics of naive, memory and effector
human CD8+ T cells can be sensitively monitored by combined analysis of membrane phenotype and expression of selected intracellular proteins. Viral infection,
including HIV-1, results in gross changes in naive and memory populations, that
in HIV-1 infection are persistent in nature.

(Cytoron Absolute with Immunocount II software) and additional markers such as
CD11a and CD62L. Results were compared to HIV-, asymptomatics (asympto)
and late stage (late) HIV+ patients. Follow-up during HAART extends up to 8
months and is still ongoing.
Results: During Al a decrease in CD4 count and % and AC of CD4 naive
cells and an increase % of CD8 naive cells was noted (Table 1). HAART was
associated with a rebound of CD4 regeneration leading to a progressive increase
in CD4 cells and its naive subset while CD8 naive cells remain stable (Table 2).
Table 1
Stage AC CD4+ AC CD4CD45RA+ (%) AC CD8+ AC CD8CD45RA- (%)
(~SD) (~SD)
HIV- n = 31 910(260) 442.6 SD = 204 (48) 513(188) 364 SD = 160 (7)
Al n = 6 345(137) 120.7SD = 50 (35) 2064(1063) 365SD = 221 (27)
Asympto n = 18 388(171) 181.5 SD = 111 (45) 1042 (415) 658 SD = 312 (63)
Late n = 9 39(23) 10 SD = 9 (23) 524 (338) 169 SD = 89 (39)

Table
Time
3 mo
6 mo
8 mo

2

AC CD4+ (~SD)
469 (93)
532(191)
727 (296)

AC CD4CD45RA+
164 SD = 43
216.3 SD = 98
265.6 SD = 92

(%)
(34)
(39)
(38)

AC CD8+ (-SD)
707 (361)
508 (218)
620 (355)

AC CD8CD45RA+
295 SD = 182
282 SD = 140
362 SD = 216

(%)
(44)
(56)
(58)

Conclusion: Perturbation of the CD4 count and the CD4CD45RA+ subset
occur at all stages of HIV infection. HAART was associated with a progressive
increase in the CD4 cells and the CD4CD45RA+ subset above the level found
in asymptomatics. These data in Al provide the positive control values on CD4
regeneration during HAART.
12191 Suppression of viremia and immune reconstitution in
seroconverting patients receiving triple antiviral therapy
L.U.C. Perrin', Gerard Alphonse Schocknel', C. Fagard2, J.P. Chave3,
D. Kaufmann4, S. Yerly', B. Hirschel', L. Perrin'. 'Laboratory of Virology,
University Hospital CH-1211, Geneva 14; 3Chemin Porchat 24, Lausanne;
4University Hospital, Lausanne, Switzerland; 2Centre Hospitalier, Annecy, France
Background: The potency of HAART to inhibit viral replication and reconstitute
lymphocyte counts might be higher in primary HIV infection than at more advanced
disease stages.
Methods: In the multicenter, open-label PHI.3 trial, seroconverting patients are
treated with a triple therapy regimen of indinavir sulfate (800 mg q8h), 3TC (150
mg bid) and zidovudine (250 mg bid).
Results:
Table. Mean changes in CD4, CD8 count and log HIV-1 RNA as compared to baseline
Month 1 (n = 35) Month 3 (n = 31) Month 6 (n = 22) Month 9 (n = 15)
CD4 count +160 +180 +263 +339
(cells/mm3) P < 0.001 P < 0.001 P - 0.001 P = 0.001
CD8 count -213 -299 -337 -321
(cells/mm3) P = 0.005 P = 0.010 P = 0.035 P = 0.112
Log HIV-1 RNA* -2.2 -2.9 --3.5 -3.5
(copies/ml) P < 0.001 P -- 0.001 P < 0.001 P = 0.001
*Lower detection limit: 100 copies/ml. At the time of analysis, 42 patients had been enrolled, of
which 35 were evaluated and 7 lost to follow-up. At baseline, month 1, 3, 6, and 9, the percentage of patients with a CD4/CD8 ratio >1.4 was 0.06, 0.14, 0.26, 0.27, and 0.40, respectively
By month 6, viremia had dropped below 100 HIV-1 RNA copies/ml in all patients.
A 24-week course of triple therapy (IDV, 3TC, ZDV) achieved viremia <100
copies/ml in all patients. The pattern of CD4 increase and CD8 decrease was
biphasic with a rapid increase/decrease during the first month of treatment followed
by a slower increase/decrease subsequently. After 6 to 9 months of treatment,
approximately one third of patients reached a CD4 count and CD4/CD8 ratio
within the normal range.
S12192 Acute primary HIV infection (APHI): A cohort description
Liliana Puga,'2, H. Jauregui Rueda2,3, A. Monticelli23, S.M. Oliva'2,
M. Burgos1, A. Molina', J. Benetucci12. 1GADIS (Argentinian Group of AIDS
Researchers), 2FUNDAI Foundation, 3FAIVIH(S) - Buenos Aires, Argentina
Objective: To describe the epidemiological, clinical and laboratory characteristics
of patients with APHI and their response to earlier antiretroviral therapy (ART).
Method: Between 1995 and 1997 we studied 11 patients with APHI, confirmed
by EIA and W.blot assay. In every case clinical examination, CD4 cells count
(flow-cytometry) and plasma viral load determination (RT-PCR) were performed at
diagnosis and every 4 months. The follow up lasted 14.3 months on average (6-24
months). 6 patients were male and 5 female; 7 heterosexual and 4 homosexual.
No IVDU was in the group. One heterosexual person was infected by needle
injury. 8/11 patients had symptomatic infections and 3 had only post-exposure
seroconversion
Results: Fever (100%), lymph node enlargement (100%) and malaise (45%)
were the most frequent symptoms. Rash was observed only in two cases (18%).
The incubation was of 48 days on average (18-130 days). At entry, the media
plasma viral load was 46.673 copies (4.6 log) and the average CD4 cells count
was 495. All the patients received ART: 3/11 with 2 NRTI and 8 with 2 NRTI+1 PI.
91% of patients decreased the plasma viral load to non detectable value at
fourth month (average decrease-2.3 log). Only one patient's determination is not
available yet.

I12190

Naive T cell subsets during acute infection (Al) with HIV
and response to highly active anti-retroviral therapy
(HAART)

Sabine Kinloch-De Loes', R.S. Tilling', W. Turnbull, M. Tyrer2, M.A. Johnson2,
G. Janossy'. ' Clinical Immunology/The Royal Free Hospital Pond Street London
NW32PF; 2Thoracic/HIV Medicine The Royal free Hospital London NW32PF, UK
Objective: To investigate recently defined unprimed or naive CD4/CD8 subsets
during Al and following HAART.
Methods: Monitoring CD4 and CD8 counts and absolute counts (AC and percentage (%) of CD4CD45RA+ and CD8CD45RA+ using 3-colour flow cytometry