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

Tu.A.513 -Tu.B.l 13

Tuesday, July 9, 1996

Tu.A.513
POPULATIONS OF DEFECTIVE HIV-I GENOMES IN PBMC CELLS INFECTED IN VIVO
Sanchez Giselle, Xu X, Chenine A-L, Chermann J-C, Hirsch I. INSERM U322, Ulnite de
Recherches sur les Retrovirus et Maladies Associees, B.P 33, 13273 Marseille Cedex 09, FRANCt_
Objective: To study the presence of complete and defective HIV genome in peripheral
blood monornuclear cells (PBMC) from people with progressive and nonprogressive HIIV
infection. In spite of enormous variability of HIV genome, occurence of extensive deletions
or other alterations in HIV DNA in vvo is poorly documented.
Methods: Long distance polymerase chain reaction (Ld-PCR) was used to amplify the HIV
DNA localized betweern long terminial repeats (LTR) present in the Ficoll-purified PBMC
from HIV infected persons. Ld-PCR followed by Southern blott hybridization with [32P]_
oligonucleotide probes derived from six distant regions spread all over the HIV genome
permitted to identify complete as well as largely deleted HIV genomes.
Results: Different populations of distinct HIV I DNA fragments of highly variable size ranging from 600 bp to full length provirus were present in PBMC from HIV-infected persons.
Defective genomes were observed in all but one of 10 studied patients. Full length HIV
DNA was missing from the Ld-PCR products of two nonprogressors. Most of defective
fragments reacted with probes specific for both extremities of HIV genome.The frequency
of deletions was proportiornal to their proximity to the central part of HIV genome. A
comparison of electrophoretic mobility of defective firagments with the expected sizes of
DNA fragments based on analysis of the hybridization pattern suggests the occurrence of
one hit deletion events and does not provide an evidence for involvement of other extensive DNA abernations in the formation of defective genomes. Defective genomes tended to
gradually disappear after activation of PBMC with phytohemaglutinin. Only full-length LdPCR product was obtained in PBMC infectedin vtro.This suggests that, in contrast to situation in vivo, defective genomes ire negatively selected in vitro.
Conclusions: We demonstrate for the first time the presence of a higlh proportion of
defective genomes involving large deletions in PBMC infected ini vivo, and provide an easy
approach to study distribution of defective and complete genomes in HIV infected persons.
G. Sanchez, INSERM Unite 322, B.P 33, 13273 Marseille Cedex 09, France.
Telephone: [phone] Fax [phone]
Tu.B.I 10
PREDICTING PNEUMOCYSTIS CARINII PNEUMONIA: RESULTS OF A
MULTIVARIATE ANALYSIS
Huang, Laurence, Hecht, FM, Gruden, JF, Kearns, K,Turner, J, Stansell, JD, Hopewell, PC.
San Francisco General Hospital, University of California, San Francisco, SF, CA, USA
Background/Objectives: PCP remains the most frequent AIDS defining opportunistic infec
tion in the U.S. Definitive diagnostic tests are expensive and, in the case of bronchoscopy,
invasive. Selectionr of appropriate patients for diagnostic testing relies on cinician experience
in evaluating clinical variables.This study determined the association of clinical variables with
PCP using bivariate analysis and the independent predictive power of these variables for
PCP using a multiple logistic regression model.
Methods: Prospective study of all patients with suspected PCP referred to the Division of
Pulmonary and Critical Care at SFGH for diagnostic evaluation over a 5 months period.
Clinical and lab variables were verified by a single researcher, chest radiographs (CXR) were
graded by a chest radiologist, and patients without a microscopic diagnosis of PCP were followed for 60 dclays to assess for the subsequent development of disease.
Results: (I) 164 patients with suspected PCP were evaluated. PCP was subsequently dingnosed in 60 (36.6%). (2) Cinical variables that were associated with PCP in a bivariate
analysis are shown 'aelow:

in the ICU (n= 20Y) rv., was 58%: 8 to 14 days (n=Il II) survival was 52%; 15 to 21
days (n=80) surviv, a: i % Patients with a prior AIDS-defining illness were less likely to
survive ICUI rc '3,,,n ' (36% vs. 55%; p-=0.004). Among patients with a prior AIDSdefining llne, r, a r ihe ICU for > 2 weeks, 0/16 survived to hospital discharge
(95% CI 0 19"? ");.,e,nt ciiaracteristics not associated with survival included age, gender,
race, HIV risk group. i n uranice status, and severity of illness on admission to the hospital
(alveolar-arterial oxyen difference, albumin, and total lymphocyte count.) There was no
association between number of days from hospital admission to ICU admission and survival
to discharge. Hospital characteristics associated with lower survival of patients cared for in
an ICU included increased HIV experience of the hospital and a teaching affiliation. Patients
cared for at hospitals with high HIV-experience and teaching affiliation were less likely to
receive care in an ICU.
Conclusions: Increased length of stay in an ICU is associated with decreased survival.
However, unlike prior reports, survival for patients in the ICU > 2 weeks was not 0, but 24%.
Patients with a prior AIDS-defining illness had a low chance of surviving to discharge after ICU
care > 2 weeks, but small numbers limit prediction. Hospital characteristics were associated
with survival after ICU care; these differences likely represent different ICU utilization pattemrns.
J. Randall Curtis, MD, MtPH, Pulmonary and Critical Care Medicine, University of
Washington, Box 359762, Seattle, WA 98195, Phone [phone], fax [phone].
Tu.B. 112
QUALITY OF LIFE IN A DOUBLE-BLIND RANDOMIZED TRIAL OF 3 ORAL
REGIMENS FOR MILD-TO-MODERATE PNEUMOCYSTIS CARINII PNEUMONIA
INAIDS (ACTG 108)
Wu, Albert W, Gray S*, Brookmeyer R5, Safin S. Johns Hopkins University Baltimore,
Maryland; i*Unversity of California, San Francisco, California, USA
Objective: To determine quality of life (QOL) outcomes in a randomized, double-blind, multicenter trial of oral trimethoprimsulfamethoxazole (TS), dapsone-trnmethoprim (DT), and
clindamycin-priraquine (CP) for treatment of mild-to-moderate Pneur ocystis ccrinii pneumonia (PCP) in patients with AIDS,
Methods: Subjects were enrolled from May 1991-June 1993. Eligible patients haid HIV infection, confirmed PCP and an alveolararterial gradient of < 45 mmHg. Study therapy was
administered for 2 I1 days ~ 24 hours. QOL outcomes were assessed using a self administered battery of scales. Physical functioning was assessed using the Duke Activity Status
Index (DASI), a 12-item index weighted on the basis of known metabolic costs of each
activity Energy, pain, and general health perceptions were measured using scales from the
MOS-HIV Disability was measured using bed days and days of reduced activity Symptom
severity was assessed for pulmonary (cough, dyspnea, chest tightness) and other symptoms
(fever, pain, nausea, rash, dizziness).The questionnaire was available in English and Spanish,
and took about 5 minutes to complete. Changes in health status scores were analyzed using
Kruskal-Wallis and Wilcoxon rank-sum tests at day 7 and day 2 I.To provide a summary sta
tistic, a random effects model was used with initial group assignment and dimension of
QOL as fixed effects, and person as a random effect.
Results: For 18 I eligible subjects, completion rates at baseline, day 7 and day 2 I were 87%,
80% and 74%, respectively Completion rates were balanced across groups at baseline and
day 7, and were h ghest for the CP group at day 21. Respondents and non-respondents
were similar at all time points. Survival, treatment failure, and incidence of adverse events
were similar in the three groups, but patterns of toxicity differed. QOL scores improved
over time for all groups. For example, by day 7 when comparing TS, DT and CP groups,
general health perception scores improved 5.6, 1.8, and 15.9 points, respectively
Multivariable analyses showed that averaged across all dimensions patients on CP reported
changes in scores about 10 points higher than patients on TS (p=0.007). By day 2 I patients
had improved further but differences between groups were less evident, with only a trend
favoring DT overTS (8 points, p=.07).
Conclusion: Using conventional outcomes, the 3 treatments were similar. Data on QOL
suggested that patents on CP recovered slightly faster than patients on TS, but that the
treatments had similar efficacy over 3 weeks. In this study, inclusion of data on patient
reported health status complemented the results obtained using other outcome variables.
Albert WWu, 624 North Broadway Baltimore, M.D., 21205 USA Telephone: [phone]
Fax [phone], email: awu@(phnet.sph.jhu.edu
Tu.B.I 13
PNEUMOCYSTIS CARINII PNEUMONIA AS FIRSTAIDS INDICATOR DISEASE IN THE
ERA OF PRIMARY PROPHYLAXIS - WHY DOES IT STILL OCCUR?
Flepp Markus, Ledegerber B. Schenker C, Egger M, M. Gebhardt**, L. Uthy R, t. he Swiss HIV Cohort
Study (SHCS). Div. of Infectious Diseases, University Hospital, Zurich and *IUMSP University of
Lausanne, *Swiss Federal Office of Public Health (SFOPH), Berne-Liebefeld, Switzerland
Objective: To examine characteristics of patients diagnosed with PcP as first clinical AIDS
indicator disease in Switzerland 1993 and 1994.
Methods: Identification of cases in the SHCS database supplemented with a retrospective
chart review. Criteria defined as indication for primary prophylaxis (PP): CD4+ cell count
<200/ul and/or CD4+ cell count < 14% and/or oral candidiasis and/or oral hairy leucoplakia
within one year of diagnoss.
Results: 145 cases, representing 57% (145/256) of all first AIDS indicator diseases (CDC87) reported to the SFOPH for the same time period. 108 patients were male and 37
(26%) female. Risk factors for HIV infection: Homosexual contacts 63 (43%), heterosexual
contacts 33 (23%), needle sharing 43 (30%) and other 6 (4%). 134/145 (92%) d d not
receive PP at the time of PcP diagnosis. I 16/145 (80%) had never received PP (Table) and
18/145 (I 2%) either had stopped PP 2 months (10) or started <2 months (4) or lacked
compliance (4) before they developed PcP
Only I1/145 (8%) patients developed PcP while receiving PR and 9 of these were not
receiving cotrimoxazole.

Variable
CD4 count<50 cells/uL
PCP prophylaxis
Absence of purulent sputum
Serun LDH>220 U/L
CXR w/ granular opacities
02 saturation <93%

Odds Ratio
2.3
9.60
3.57
30.45
2.79

p Value
0.027
0.025
0.00 I1
0.03
<0.000 I
0.002

Results: of a multipe logistic regression model:The strongest independent predictors of
PCP were a CXR with granular opacities (OR-66.9, p=0.000 1), a CD4 count<-50 cells/uL
(OR= I O1.0,p-=0.009), and absence of purulent sputum (OR=43.5,p=0.004). No patient with
purulent sputum and a CXR without granular opacities had PCP
Conclusions: (I) The strongest independent pr edictors of PCU ' are a CXR with granular
opacities, a CD4 count <50 cells/uL, and the absence of purulent sputum. (2) The combination of purulent sputumr and a CXR without granular opaci ties indicates a low rsk for PCP;
these patients should be treated for another process and do not need to undergo diagnos
tic teting for PCP
Laurence Huang, MD Division of AIDS/Oncology Ward 84 AIDS Program, SFGH 995
Potrero Avenue, San Francisco, CA 94 110 USA Telephone: [phone]
Fax: [phone], email: LHUANG eITSA.UCSF.EDU
Tu.B.I II
SURVIVAL FROM INTENSIVE CARE FOR PATIENTS WITH HIV-RELATED
PNEUMOCYSTIS CARINII PNEUMONIA (PCP)
Curtis,I Randall*, Hoer RD**, Bennett, CL*-*. University of Washington, Seattle WA;
"**VA Medical Center Durham, NC; ***Lakeside VA Medical Center, Chicago IL; USA.
Objectives: Two small studies have reported that no patients survived after 2 weeks in an
intensive care unit (ICU) for PCP suggesting that ICU care should be withdrawn after 2
weeks.The goal of this study is to examine the association between length of stay in an ICU
and survival to hospital discharge for patients with HIV-related PCPR
Methods: Chart review of a representative sample of patients with HIV-related PCP hospitalized in a random sample of 73 pinvate, 9 public, and I4 VA hospitals in Chicago, New
York, LA, Miami, and Durham, NC, from 1987 to 1990.
Results: Data were collected for 2174 patients with PCP of whom 398 (18%) were cared
for in an ICU. Of the patients cared for in an ICU, 197 (49%) survived to hospital discharge.
Survival to discharge was strongly associated with length of stay in the ICU: for I to 7 days

Unaware of HIV status
Not in care 1 Iyear
PP declined
PP not offered
Did not qualify for PP

37/1 6 (32%)
481/ 116 (35%)
18/I 16 (16%)
18/116 (16%)
2/116 (1.7%)

229