Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Monday, July 8, 1996

Mo.B.3 1 3 - Mo.B.41 I

Some retrospective studies showed thatTMP-SMZ is effective in (71 in AIDS patients.To
determine the efficacy and tolerance ofTMP-SMZ versus standard therapy pyrimethaminesulfadiazine (PS), a multicentered, prospective. and randomized trial was designed.
Methods: One hundred and two AIDS patients with CT have been enroled in 21I
Departments of Infectious Diseases, treated with TMP-SMZ (TMP: 10 mg/Kg/die, SMZ:50
mg/Kg/die) or PS (P:50 mg/die, S:60 mg/Kg/die). Patients with stable o mproved disease, as
evaluated by cerebral tomography imaging and clinical examination,,cere continued on
therapy We report preliminary data on 51I patients (35 men, 16 women), mean age:
33.2 +-5.4 years.
Results: Fourteen of 26 patients (53.8%) treated with TMP-SMZ ad 14 of 25 patients
(56%) treated with PS showed complete regression of clinical signs, whereas 7 patients
(26.9%) treated with TMP-SMZ and 10 patients (40%) treated with PS were unchanged or
worsened. Regarding evaluation of the radiologic response, 14 patients (53.8%) treated with
TMP-SMZ and 7 patients (28%) treated with PS had resolution of radiological signs (P=.042,Fisher's exact test). In contrast, 8 patients (12%) treated with IP-SMZ. and 8 patients
(30.7%) with PS were unchanged. Adverse events were noted in 4 patientrs (7 8%): 2
patients treated with TMP-SMZ and 2 with PS.Two patients treated with TMP SMZ, and 2
with PS relapsed, after a 3 month-period of follow-up. A patient (3.8%) treated with TMPSMZ and 3 (I 2%) with PS died during the follow-up period.
Conclusion: These results suggest that TMP-SMZ is an effective drug for the treatment of
CT in AIDS patients.TMP-SMZ appears to be an acceptable alternative in comatose
patients (intravenous administration), and it is also effective against Pneumocystis carirnii and
other opportunistic bacterial pathogens.
D.Torre, Department of Infectious Diseases,Viale Born 57,21 110 Varese, Italy
Telephone: [phone] Fax: [phone]
Mo.B.3 13
CEREBRAL DENDRITIC ARBORIZATION IS ASSOCIATED WITH DEGREE OF
COGNITIVE IMPAIRMENT IN HIV INFECTION
MarcotteThomas D*, Masliah E*, Heaton RK*, Ellis RJ*, Wiley C* 'Mallory Mm, McCutchan
JA*, Atkinson JH*Grant, Igor*the HNRC Group. *University of Cilforne San Diego, CA,
USA; **Presbyterian University Hospital, Pittsburgh, PA, USA
Objective: To determine if cortical dendritic arborization, assessed at autopsy correlates
with cognitive functioning during life in individuals who had HIV infe-hore n and varying neurocognitive impairment.
Methods: Midfrontal cortical sections from 19 subjects who received a comnprehensive neuropsychological (NP) and neurological assessment within I 8 months of death were
imrnmunostained to determine the percent of nreuropil covered with dendrites. Prior to
death, all cases were diagnosed as to whether they were cognitively Normal or met criteria
for Minor Cognitive Motor Disorder (MCMD) or HIV-Associated Dementia (HAD).
Subjects with NP impairment who did not meet syndromal criteria were called NP
Impaired (NPI).
Results: The mean time between assessment and death was 232 (SD= I 16.3) days. Nine
subjects were diagnosed as cognitively Normal, 5 were NP ImpairedI 4 mnet M:MLD criteria,
and I met HAD criteria. Dendritic percentages were significantly differerent among the
groups (p =.00 I), with the Normal subjects (mean = 20.5) consistently higher than
MCMD (mean = 13.3) and HAD (12.5) subjects.The NPI subject, (mean = 17.3) had
counts that generally fell between subjects with Normal NP functioning and those with syndromal impairment.There was a strong correlation between postmortem dendritic complexity and overall NP functioning (r -.67; p =.002), as well as with specific perceptualmotor, abstraction, learning, and verbal abilities.
Conclusions: Injury to the neuronal dendritic structure in the midfr ontal lobes is strongly
associated with pre-agonal cognitive functioning, and it appears that a threshold of damage
must be reached for cognitive impairment to become overtly symptomatic.
Igor Grant, 2760 Fifth Avenue, Suite 200, Sanr Diego, CA 92103 USA
Telephone: [phone] Fax: 619-543- I 235 email: [email protected]
Mo.B.314
CEREBROSPINAL FLUID (CSF) HIV- I RNA LEVELS CORRELATE WITH AIDS D
EMENTIA COMPLEX (ADC)
Brew Bruce J*,*-, Pemberton L**, Cunningham P*-" Law M***. 11 V Medicine and
Neurology Departments *"Centre for Immunology St Vincents Hospitali *-"National
Centre in HIV Epidemiology anid Clinical Research St Vincent's Hospital Sydney Australia
Objectives: To determine the relationships between levels of CSF HIV- I RNA and i) the
presence and severity of ADC, ii) central nervous system (CNS) infections and iii CSF 02
microglobulin and neopterin levels.
Methods: 26 patients were assessed neurologically neuropsychologir:aly, by CF brair iscan
anrid CSF analysis, with different severity of ADC: 6 stage 0, 8 stage 1, 6 stage 2 and 5 stage
3.There were 10 stage 0 patients with CNS infections: 7 with cryptococcal meningitis, 3
with progressive multifocal leukoencephalopathy (PML). HIV -I RNA was e trarted from the
CSF of all patients and from the plasma in 10 of the ADC patients (stages- I and 2) and
quantified by RT-PCR amplifying a I42 base pair fragment of the ga0,-,in R che)
Results: CSF HIV- I RNA load was 36,824~14,845 copies/ml for stage 21 while in the plasma it was 567, 1I6~ I18,296 copies/ml (median difference 31,700, p<U.01).T here ws a significant correlation between increasing severity of ADC and HIV I RNA bur er,r, the CSF
(p=0.002) but not in the plasma. CSF HIV- I RNA in cryptococcal meningitis was
94,771~38,838 copies/mI and in PML 208+ 152 copies/mI.There wa isno relaionship
between CSF HIV I RNA levels and blood brain barrier impairmert, the nurrber of CSF
white cells except for those with CNS infections. Levels of CSF HiV I dNA were more
highly correlated with CSF 132 microglobulin than neopterin.The sesirvity spe, I ily predictive value, false positive and false negative rates of CSF HIV I RNA IOOQ copies/ml for
ADC stage >1 are 58%, 83%, 92%, 8.3% and 61% respectively.
Conclusions: CSF HIV- I RNA levels correlate with ADC severity but may aiso be increased
by CNS infections such as cryptococcal meningitis. In appropriate patierts (SF HIIV- RNA
levels can be used as ancillary measures in the diagnosis of ADC.1he rla, ns ip to ADC
supports the pathogenetic role of HIV- I but the relatively small CS -r icad and high false
negativity rate suggest indirect mechanisms.
Bruce ) Brew NCHECR 376 Victoria St Darlinghurst Sydney Austrl. i a

Fax:6 I 2 332 i 837 Email: [email protected] ph:612 332 342 I

Mo.B.315
EVIDENCE FOR BIOCHEMICAL CHANGES IN THE FRONTAL LOBE OF HIV
INFECTED INDIVIDUALS WITHOUT ADC
Lenkinski, Robert E, D. Lopez-Villegas D, Frank I. University of Pennsylvania,
Philadelphia PA, 19104, USA
Objective: There has been recent interest in employing proton Magnetic Resonance
Spectroscopy (MRS) to study the effects of HIV infection in the CNS. Since it has been
shown that neuronal damage occurs in the intermediate or late stages of disease our goal
was to determine whether MRS could detect metabolic alterations in the brain before
there was any clinical evidence of disease.
Methods: We have implemented and validated an MRS method capable of sampling voxels
small enough to provide "pure" spectra of cortical gray matter and selected white matter
regions.We have employed this method to study a population of 15 HIV-I infected subjects
(I I men and 4 women). Each subject underwent neurological, psychiatric and neuropsychological (NP) examinations. All of the patients had CD4 counts less than 200 cells/mL at the
tnme of evaluation. Utilizing both neurological and neuropsychological evaluations 8 patients
were classified as ADC 0. Five patients presented with mild and 2 patients with moderate
degrees of ADC (ADC 1/2), respectively
Results: MRS shows two different abnormalities as compared to normal controls: a
decrease in NAA peak in gray matter; and an increase in the myo-inositol (ml) peak in
white matter.The group of patients with ADC showed a significant decrease in NAA/Cr
ratio in gray matter in comparison with the control group and with the group of patients
without ADC.The group of patients without ADC was characterized by an increase in
ml/(Cr levels in white matter and normal levels of NAA/Cr in both gray and white matter in
conmparison with the control group.
Conclusions: These results suggest that the evaluation of frontal lobe metabolism by high
resolution MRS will identify early changes in brain metabolism that precede the damage of
neurons, helping to select patients for possible therapies before irreversible damage may
occur Additionally, this MRS approach may be a good method to objectively evaluate the
clegr no and progression of ADC and to monitor the effect of therapy
RE Lenkinski Ph.D., Dept. of Radiology Hospital of the Univ. of Pennsylvania, 3400 Spruce
Street, Philadelphia, PA 19 104
Mo.B.410
SAQUINAVIR (INVIRASE, SQV) VS. HIVID (ZALCITABINE, DDC) VS.
COMBINATION AS TREATMENT FOR ADVANCED HIV INFECTION IN PATIENTS
DISCONTINUING/UNABLE TO TAKE RETROVIR (ZIDOVUDINE, ZDV)
Sal go, Miklos P, Beattie D, Bragman K, Donatacci L, Jones M, Montgomery L, the NV14256
Study Teamn. Hoffmann-La Roche, Inc, Nutley, NJ, USA
Objective:-1 he objective of this randomized, double-blind, phase II/Ill, multicenter study was
to compare the safety, tolerability and efficacy of SQV and ddC, alone and in combination,
based on clinical endpoints and laboratory markers of immunological and virologic activity
Methods: A total of 978 HIV infected patients with a screening CD4 lymphocyte count of
50 300 cells/mm3, and a minimum of I 6 weeks of prior ZDV therapy were randomized to
receive ddC 0.75 mg q8h, SQV 600 mg q8h, or SQV 600 mg + ddC 0.75 mg q8h.
Laboratory marker data (CD4 lymphocyte response and changes in viral load as HIV- I
RNA) from a planned interim analysis of surrogate marker activity from 45I evaluable
patients who had received a minimum of I 6 weeks treatment, or who had dropped out
before 16 weeks, are presented.
Results: Patients randomized to the SQV + ddC group had a higher and more sustained
increase in CD4 lymphocyte counts, as measured by the DAVG I 6, compared with patients
in the ddC group (p<0.00I) and in the SQV group (p=0.001).The difference between
SQV and ddC was nriot significant (p=0.12).The median DAVG values were 26 cells/mm3
for the SOV + ddC group, I10 cells/mm3 for the SQV group, and 3 cells/mm3 for the ddC
group. Similarly, combination therapy produced a greater and more sustained decrease in
viral load than either monotherapy (p<0.00 I).There was a statistically significant difference
in viral load. favoring ddC, between the SQV and ddC groups (p=0.00 I).The median
DAVG I 6 values were -0.6 log 10 copies/mL for the SQV + ddC group, -0. I log 10
coples/mL for the SQV group, and -0.3 log I0 copies/mL for the ddC group. SQV was well
tolerated alone and in combination with ddC.
Conclusions: The combination of SQV + ddC was associated with greater increases in
CD.4 lymphocyte count and greater suppression of viral load, as measured by HIV- I RNA,
than either S(QV or ddC monotherapy
Miklos P Salgo, M.D., Ph.D., Hoffmann-La Roche, 340 Kingsland Street, Bldg 719/3rd FI,
Nutley New Jersey 071 I O.Tel: (20 I) 8 I 2-3587 Fax: (20 I) 8 I 2-3629
Mo.B.41 I
PROLONGATION OF LIFE AND PREVENTION OF AIDS COMPLICATIONS IN
ADVANCED HIV IMMUNODEFICIENCY WITH RITONAVIR: UPDATE
Cameron D.W, Heath-Chiozzi M, Kravcik S, Mills R, Potthoff A., Henry D,The Advanced
HiIV Ritonavir Study Group and Leonard J. Abbott Laboratories, Abbott Park. Illinois USA,
cUniversity of Ottawa at Ottawa General Hospital, Ottawa, ON, Canada
Objective: Ritorair is a potent, orally bioavailable HIV protease inhibitor.We designed and
conducted an i;ternational multi-centre randomized placebo-controlled clinical trial of ritonavi 600 mg twice daily for outcomes of death and new AIDS-defining illnesses or selected
recurrences (pneumocystis pneumonia, esophageal candidiasis, and chronic herpetic ulcer).
Methods: 1090 HIV patients with CD4 T lymphocyte count under 101 cells/mm3 and over
rnme irinthrs am ior anti -HIV therapy were randomized in 68 North American, European and
Autralin cenres, fon April to July 1995. Concurrent anti-HIV therapy was permitted.
tirossoe to open rntonavir for any AIDS outcome was provided after four months on
study Fir0 ai4iysis was conducted in January 1996.
Results: Baseinne characteristics did not differ; with median CD4 1 cells 18/mm3 (mean 30,
stanard dmvarion 28) in ritonavir and 22/mm3 (mean 35, standard deviation 28) in placebo groups. Drug discontinuation associated with adverse events occurred in 91 (17%) of
54 I rtonavin versu 32 (6%) of 547 placebo patients. Events included nausea, vomiting,
weakness rid di rhea m ostly beginning during the first two weeks on study. In nmedian 6. I
(rme 0 2 to 7.7) months follow-up, 26 (4.8%) ritonavir versus 46 (8.4%) placebo patients
di,,~ed p=002,hazrd ratio 0.57, 95% CI 0.35 - 0.92). Outcomes of either AIDS or death

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