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

Tu.B.2288 - Tu.B.2292

Tuesday July 9, 1996

Method: HIlVinfected subjects who had developed non-anaphylactoid hypersensitivity reactions (fever, rash, itch) whilst receiving TMP SMX for Pneumocystis carinii pneumonia prophylaxis were recruited. MP SMX wais administered orally in increasing doses five times
daily comrririencing with Ioug SMX.The final dose, 400mg SMX was reached on the fourth
day and continued daily. Subjects were monitored in an outpatient department for 6 hours
or t'fi rst day they were then observed briefly on days 2, 3and 4 and subsequently followed for 12 months. Subects who developed recurrence ofTMP-SMX hypersensitivity
continued takingTMP SMX it a reduced dose and then increased the dose more gradually
accrding to a "rescue' protocol Moderate hypersensitivity reactions ( e.g. fever, itch, confluent r ish) were treated with short courses of prednisone. Failure was defined as inability to
take FMP-SMX because of continred hypersensitwty reactions.
Results: 21 sub ects were recruiled. r6/2 (76%) subiects were successfully desensitised. 2
of / subject who iniially developed hypersensivty reactions up on rechallenge were able
to tolerite TMP-SMX after completing the "rescue' protocol. Successful desensitisation was
more coiron in patients who td exper enced a LD4 cell count decline since their initial
TMP SMX hypersensivti forveaction (x > 0.05). No serious adverse events occurred. 14 of
4 sbects who were successfully desensitised and were being followed at 12 months contnued to tolerate TMP-SMX.
Conclusions: TMP SMX desensitisation is iafe effe tive and an be conducted in the outpatient setng. 76% of subjects previously hypersensitve to prophylactic doses ofTMPvSMX
were successfully desensitised. As TMP SMX remains the most effective agent to prevent
PC.Pf in HIV infected sifict desensitisaton should be consicered in all previously hypersensl ve subjects.
Mark Kelly, Inflammatiorn Researich Unit. School of Pathology, University of New South
Wales, NSW 2052, Austr iia. Tel.: [phone] fax: [phone]
Tu.B.2288
AIDS,TOBACCO SMOKING, PNEUMOCYSTIS CARINII PNEUMONIA, AND
SURVIVAL TIME
Pereia Cistiane M, Schlatter D, Franke LA, Keffer CP Hospital de Clinicas de Porto Alegre,
Bras,
Objective: Study the influence of tobacco smoking and the occurrence of Pneumocytis
pneumonia (P(CP) and survival time in patients with AIDS.
Population & Methods: A cohort of patients with AIDS diagnosis was establish in 1991 at
Hospital de Clinicas de Porto Alegre, a national AIDS reference center in Brazil. In this
serie, it included 302 patients who died until december 1995. A total of 243 patients
were considered elgible (the others were lost to follow up or had a non AIDS related
deat evi n). In this group. 207 (85%) were men, and 36 (I 5%) women; the majority of
them acqu red HIV infection through sexual contact (>than 90%). A PCP episode was diagnosed according to the CDC definition critena.robacco smoking was defined positive until
6 months before the AIDS definng event (99 smokers and 144 non-smokers).
Results: PCP wa diagnosed in 9/ paients (40%) of these patients, 28 were smiokers and
69 r>n -smoker s (relative ik of 0.59, 0.42 to 0.85, 95% confidence interval, with p=-0.002).
ihere was no difference according t o sex or race.The mean survival time of both groups
(smokers and noni smokers) w as absolute the same (20 months). The PCP group had a
eai srvival time of 21 months versus 18. months in the ionPCP group.
Conclusion: Althou h stll unexplai ed, these findng su ggest that smokers are at lesser risk
ito dveop P(P (0.59, 0, 42 to 0.85) In these series there was no difference in the survival
tie etweer smokers and nonr -smokers after AIDS diagnosis. Other studies are necessary
to exii rn the possible protector role of tobacco smoking against PCP
part ly sppo rted by interrnationral AIDS training g rant #D43Tv0000-03, "Fogarty
Ine r,,i on Center', NIfI
Criitne Perera. Hospital de Clinicas de Porto Alegre. Rua Fernandes Vieira 238/701. Porto
Alegre' RS Brasil Tel: [phone] Fax: 55-5- f330-1618
Tu.B.2289
META-ANALYSIS OF PROPHYLACTIC TREATMENTS AGAINST PNEUMOCYSTIS
CARINII PNEUMONIA AND TOXOPLASMIC ENCEPHALITIS IN HIV-INFECTED
PATIENTS
Bucher Heiner C'*, Griffith ', uyatt (H', Opravil M*'. *McMaster University Hamilton,
Ontar i, (irnada, Univer sity Hospital Zurich. Zurich. Switzerland
Objective: In a systemtic overview we exinamined the efficacy of aerosohzed pentamidine,
tIi i illopc tm-sulphamethoxazole and dapsone or dapsone/pyrimethamine for the preventrof Pneumocystis car n pneumonia and toxoplasmic encephalitis in patients with HIV
infection.
Methods: We dentified all randomized controlled trials published through May 1995 and
examined progression to Pneumocystis carinii pneumonia or toxoplasmic encephalitis, death
and d rug intolerance. Of 2 randomized controlled trials, 13 compared trimethoprim sul
faimethoxazole versus aerosolized pentamidine, 9 compared dapsone alone or in combina
tion with pyrnmethamine versus ierozolized pentamidine, and 8 compared trimethoprimsulf, iii thifvitOe versus d ipsonc'/pyr iirifeth ine
Results: 1,484 pt ents eiri t-ete ihtr n xfopicm-sulfissethoxazole, 1,547 patients
with dlpsone/pyrnisetham ne or dapone, and 799 patients with aerosolized pentamidine.
For d psone/pyr imethamine versus aerosolized pentamidine the risk rat io for Pneumocystis
ciirini picitooerr was090 9S% CI.71 to I. tiff ndor toxoplismic encephrlrtis0.72 (Cl
0O4 t r.97 Fo me thi p rx ul rf thazo us roolozed aorosolized pentamidine Ire riCkirstir f Pnseuo cystis iar i prrurnim wis 0.59 (CI 0.45 to 0.76) ard for
toxopasi orscephashts C.78 (Cl 0.55 ii I. II. For Iirirotfoprim- u linseihoxazole versus
dpor epyrirethaiie ifd ris r si Pneumocyst ciii pneumoni wa 049 (C 0.26
to 0)2) c 0 it ox phh enreph it I 17 ( I.68 to 2.18). Risk rio of mortality for
tri nethopim-sifrsethoxizolo corsprecd to retosolted aorosolized pentrosidine was 0.88
(Cl 0./4 'ti 3.6) ind corspred ii dap~srone/pyrimerthimice in subjects with <100 CD4
cell si ri's 0.43 CI 031 to 088. For dipsoepyrsoethainre veisus rerosol ted penor d0n riskc ratio for-rot oeraore wis v.08 fCI i"'3 to.3). For trimethoprime-suof
faisetfhox itile verstir aercisrlted port icrndinse r-isk rario for intolerance was 4.05 (95CI
2.40 io 6.83 fanid for imetshfpr imi-s ifaimroihoxitole ver sOs dapsone/pyr methamune I.05
IC f.8lt 1.25.

Conclusions: Current evidence supports the administration of trimethoprin sulfarmethoxa
zole for prophylaxis of Pneumocystis carinii pneumonia. For prophylaxis of toxophismosis
dapsone/ pyrimethamine is superior to pentamidine but not more effective than trimetho
prime-sulfamethoxazole.
H. C. Bucher, Department of Clinical Epidemiology & Biostatistics. McMaster LUnivers 5ty
1200 Main Street W, Hamilton, Ont, Canada,. L8N 3Z5. Phone [phone]. Fax 905 577
0017
Tu.B.2290
HIGH DOSE AEROSOL PENTAMIDINE FOR SECONDARY PROPHYLAXIS OF
PNEUMOCYSTIS CARINII PNEUMONIA IN PATIENTS INTOLERANT OF OTHER
SYSTEMIC THERAPY
Lee-Pack Leslie, Favell K, Lewis C, Moore M, Chan CK. The Toronto Aerosol Pentamidine
Clinic, University ofTorontoToronto, Canada.
Objective: To describe the pr agmatic use of high dose aerosol pentarni dine (AP n the secondary prophylaxis of pneumocystis carins pneumonia (PCP) n n yroup of AIDS patients
intolerant of other systemic prophylaxis therapies.
Methods: A small group of 14 AIDS patients who developed one or more episodes of PCP
despite being on AP prophylaxis but who were also intolerat ofTMP/SMX, Dapsone, aid
were started on high dose AP protocol. Surveillance included monthly outpatient AP clinic
visits for breakthroughs, regular- spirometry to assess bronchospasm and regular- 6-month
chest x-ray plus prompt investigations with any decne in the respiratory status. AP was
administered in the standard protocol by dissolvingl 300 mg of pentami dine in 5 ml of ster
ile water and aerosolized by Respirgard II device. With the high dose protocol, the patients
received 300 mg every 2 weeks (600 mg/month). Spirometry,was done pre- and post
treatment of AP
Results: These 14 subjects were on conventional dosage (300 rmg/month) AP for -an aver
age of 8 months prior to switching to the high dose (600 mg/mronth) regimen. All subjects
had at least one episode of PCP despite being on 300 mg/month AP prophylxis.They have
all beer tried on desensitization to systemic therapy and filed. At the time of preparation
of this abstract, this group of 14 patients received high dose AP for an average of 7 months
(range: 2 to 31 months). Eight patients died and 6 patients remained on the high dose pro
tocol.There was no clinical/radiological/pathological proven episode oft PCP dunng this follow up period.The incidence of cough and bronchospasm was not any higher with the high
dose AP compared to the self-controlled data while they were on the conventional dose of
AP
Conclusions: These preliminary data on a small but exceedingly hih rissick groupof
patients would suggest that the effectiveness of AP for PCP prophylaxis can perhaps be
enhanced by increasing the dosage.Acute pulmonary toxicity is not increased bu t longterm
toxicity remains to be evaluated.
L. Lee -Fiack, c/o Dr. C. Chan, 200 Elizibeth Street, 0EN 220, Toonto, Ontario. MSG 2C4
Canada Telephone: [phone], Fax: [phone]
Tu.B.229 I
EFFICACY AND SAFETY OF TRIMETHOPRIM-SULFAMETHOXAZOLE DESENSITIZATION IN PATIENTS INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS
Caumes E, Guermonprez G, I ecomte C, Katlama C, B,c,ire F. Servicedes Maladres
Infectieuses et Tropicales, H6pital Pitie Salpitrnere, Pans. France
Objective: We evaluated the safety and efficacy of triiethoprcr sulfiamethoxazole
(TMPSMX) desensitization in 48 previously hyper-sensit,ve patent rs infected with the human
immunodeficiency virus (HIV) and we described factors assor,ted with failure of this procedure.
Methods: All HIV-infected patients with a history of allergic reactons to TMP- SMX and
requiringTMP-SMX prophylaxis were eigible. Inclusion cr iteri wre cutaneous adverse
reactions (e. g. rash) attributable to TMP- SMX.The study was pedormed between
September 1993 and April 1995. The desensitization procedure took two days The full
dose (80 TMP 400 mg SMX) was reached on the 3rd day.The mir end point was the
onset of cutaneous side-effects attributable to TMP SMX within 3 months after dcesenstization.
Results: Thirty seven patients (77%) tolerated TMP SMX desensitzation without tfoxicity
and renmained on dailyTMP-SMX (median follow-up, i6 months;: irnge 5 to 2 4months).
Desensitization failed in II cases (5 on day I, 3 on day 2 and I each on days 9, II and 90)
One of these patients, a 48-year old man with a h istory of atheromatous disease, devel
oped acute hypotension and non fatal mnyocardial rinfarction. he piriameters predictive of
failure were a relatively high CD4+ cell percentage (I % versus 8%; P=0.008) and a reltively high CD4+/CD8+ ratio (0.27 versus 0.12; P-0.022).
Conclusion: As this desensitization procedure was not as safe, previously repot ted, we
suggest that TM'P-SMX should be reintroduced very carefully i e. in hospital). and that reintroduction should be contraindicated in patients fr whom acute iypc tension could have
disastrous consequences.
E Caumes, Servce des Mtladies Inecteuses et Topica es, FH'pt Pin Spy-ixtre. -7
boulevard de!'FHpitaI, 75652 Puni Cedev 3 ohl 'i2 f60 1 Fix: 4' 2404O
Tu.B.2292
REDUCING THE INCIDENCE OF PNEUMOCYSTIS CARINII PNEUMONIA (PCP):A
PERSISTING CHALLENGE
C. Pradier*, B. Dunais*, C Benttz* N. r in* (eP Cassuto' D P Darn n". P Dellamonica'
CISI, ueInternol Medhcine Depirtnient. Nie Uivers t lvirako Fran e
Objective: To evaltate the respective parts of prophyltvns finurc. lack if toedIo flow urp
and absinoce of HIV screening n the aoinrne of first cpushdes of P0 P fbetwen
1991 1/992 vnd 199301994.
Method: Dvii were retrospectuvely reviewed fr-om thc' [MI-2 diii brse ofifhe N cc'
Driver-sot / fospital, which has been gather rug mcd Incr n n ',intrti e nor rastiion iros
over 5,0,30 HIV-infected patients since 1988. Datc of roe hir s knowca pos tire 'et for- fIV,
frequency of hospital attendance piioi to PCP diagnosis nd ciato oI d rynosis were ruma
lyzed. Rates of prophylaxis failure mod prophyiaxs nter-n ptr wire estcrated.

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