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

298 Abstracts 22179-22183

12th World AIDS Conference

22179 Withdrawal of primary prophylaxis against P.cariniiand
T. gondii in adult HIV-1 infected individuals with stable
CD4 cell count above 200/LL
C. Tortajada, E. Martinez, J.M. Miro, A. del Rio, J.M. Gatell. Hospital Clinic,
Barcelona, Spain
Background: Primary prophylaxis (PP) against P carinii and T gondii is recommended for adult HIV-1 infected patients whose CD4 cells decrease below
200/IL, even though subsequent cell measurements increase above that count.
Highly active antiretroviral therapy (HAART) allows a great proportion of patients
to accomplish sustained virological and immunological responses arising the
possibility that PP against P carinii and T gondii may be not needed.
Objective and Methods: We designed an open randomized study to test
this hypothesis further. Adult HIV-1 infected patients seropositive for T gondii
were enrolled if: they were clinically stable, their plasma viral load was <5000
copies/mL, and their CD4 count was >200 cells/,L, for at least the previous 3
months. The primary end point was the development of P carinii pneumonia or
T gondii encephalitis. Secondary end points were: withdrawal from the study,
toxicity due to prophylaxis, development of bacterial infections, and death.
Results: At a first interim analysis, 68 patients could be evaluated. The arm
with prophylaxis included 29 patients and the arm without prophylaxis include
39 patients (5 patients in the prophylaxis arm voluntarily stopped primary prophylaxis against their initial randomization and they were finally included in the
no prophylaxis arm). Male:female ratio was 2.6. Nine patients (13%) had prior
category C events. Antiretroviral therapy mainly included two nucleoside reverse
transcriptase inhibitors (NRTI) and one protease inhibitor; nine patients (13%)
were receiving a combination of 2 or 3 NRTI. Primary prophylaxis consisted of
cotrimoxazole (n = 25, 86%) and dapsone/pirimetamine (n = 4, 14%). There
were no differences in sex, prior C category events, antiretroviral therapy or prior
primary prophylaxis between both arms. After a median follow-up of 16 weeks
(range: 2-46), no patient in any arm developed P carinii pneumonia or T gondii
encephalitis. Nine patients were withdrawn from the study: 4 in the prophylaxis
arm (2 were lost for follow-up and 2 had a decrease in CD4 cells below 200/pL)
and 5 in the no prophylaxis arm arm (1 were lost for follow-up and 4 had a decrease in CD4 cells below 200/ti L). No toxicity due to prophylaxis was observed
in the prophylaxis arm. There were not bacterial infections, nor deaths in any of
both arms.
Conclusions: Although the sample size is small and the follow-up is short,
these preliminary data do not argue against the possibility that PP against P
carinii and T gondii may be safely withdrawn in adult HIV-1 infected individuals
with stable CD4 count above 200 cells/p L.
22180 Is it safe to stop primary PCP prophylaxis in patients
treated with antiretroviral combination regimens?
Hansjakob Furrer1, M. Opravil2, E. Bernasconi3, D. Anwar4, M. Battegay5,
A. Frank6, A. Telenti7, M. Rickenbach8, M. Egger9, R. Maliverni1. For the Swiss
HIV Cohort Study; 1Med Poliklinik Inselspital, CH - 3010 BERN, 2University
Hopital Zurich, Zurich; 3Regional Hospital Lugano, Lugano; 4 University Hospital
Geneva, Geneva;5 University Hospital Basel, Basel 6 Cantonal Hospital St.
Gallen, St. Gallen; 7 University Hospital Lausanne, Lausanne;8 SHCS Data
Center, Lausanne; 9 University of Bristol, Bristol, Switzerland
Objective: To assess the safety of stopping primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients on antiretroviral combination therapy
who responded with a rise of CD4 cells to >200/1il and i/ 14%.
Design: Swiss HIV Cohort Study (SHCS), a prospective multicenter cohort
study of HIV-infected adults.
Methods: SHCS participants on primary prophylaxis against PCP and antiretroviral therapy are invited to stop prophylaxis if their CD4-count has been
>200//tl and >14% for at least three months. PCP prophylaxis is withheld as
long as the CD4 counts remain above these threshold values. Stopping primary
prophylaxis will be considered safe if an incidence of >3/100 PCP events per 100
patientyears (pyrs) can be excluded with 95% confidence.
Results: As of january 15 1998, a total of 100 patients were enrolled. The
present analysis is based on the 53 patients (35 male, 18 female) with a follow-up of more than 3 months (mean 5.1 months); the total follow-up period
was 22.6pyrs. The lowest median CD4 count ever measured before starting
antiretroviral combination therapy was 130/pl (range 0-200). Median CD4 count
at the time of stopping prophylaxis was 338/l1 (range 237-806). All the enrolled
patients remained above the defined CD4 count limits during follow-up. As no
case of PCP or cerebral toxoplasmosis was diagnosed so far, the incidence is
0/100 pyrs. However the upper 95% Cl is 13.3/100 pyrs.
Conclusion: These preliminary data suggest that stopping primary PCP-prophylaxis in patients with CD4 counts rising from <200 to >200 may be safe.
However, longer follow-up time is required to exclude with 95% confidence an
incidence of 3 or more PCP events per 100 pyrs. Data from a total follow-up of
approximately 100 pyrs will be available in june.

22181 A randomized trial of cotrimoxazole and
dapsone-pyrimethamine for primary prophylaxis of P.
carinii pneumonia (PCP) and toxoplasmic encephalitis
(TE)
Rita Murri1, A. Antinori2, P. Pezzotti3, A. Ammassari2, A. Cingolani2, A. de
Luca2, L. Ortana2. Department of Infectious Diseases-Catholic University-L. Go
A. Gemelli-8-Rome; 2Depart. Infect. Dis.-Catholic University Rome, 3Centro
Operative AIDS-Ist. Sup. Sanita, Italy
Design: randomized, open, controlled study. Inclusion criteria: HIV infection, CD4
< 200/pl. End-points: PCP or TE episodes, bacterial infections, death, drugrelated discontinuation. Initially pts were randomly assigned to a) cotrimoxazole
(CTX) 1 DS tablet daily, or b) dapsone 50 mg daily + pyrimethamine 50 mg weekly
+ folinic acid 25 mg weekly (DP); stratifying variable was the anti-Toxoplasma
serology. Enrollment started in May 93. Statistical analysis: Intention-to-treat criteria with survival and cumulative risk of PCP and TE estimated by Kaplan-Meier
method. Cox regression was fitted after adjustment for baseline and time-dependent covariates.
Results: At November 96, 244 pts were enrolled (122 to CTX and 122 to DP).
Median follow-up were 592 days (647 days for CTX group and 521 days for DP
group) and two groups were homogeneous for all baseline characteristics. PCP
episodes observed from enrollment to May 95 were 13 in DP group and 3 in
CTX group (HR: 4.8; 95%CI 1.4-16.8). From May 95 the dosage of dapsone was
increased to 100 mg daily, and until November 96 further 6 episodes of PCP were
observed, 4 in DP group and 2 in CTX group (HR 2.46; 95%CI 0.5-13.4). Risk of
PCP in DP group was 2.6 (95% Cl 0.5-13.7) in pts starting with CD4 > 100//11,
and 5.6 (95% Cl 1.5-20.6) in those with CD4 < 100//d1. TE episodes observed
during the entire period of study were 3 in CTX and 2 in DP. Cumulative risk of
death was 1.18 (95% Cl 0.81-1.73) for pts assigned to DP. Episodes of bacterial
infections were 56 in DP and 55 in CTX group (HR: 0.98; 95% CI 0.67-1.45).
At multivariate analysis, adjusted risk of bacterial infections was 14.3 (95% Cl
9.3-22.1) for patients previously admitted to hospital.
Conclusions: Compared to dapsone at dosage of 50 mg, CTX was more
effective for PCP prophylaxis, while efficacy of dapsone at dosage of 100 mg was
similar to CTX. Comparison of efficacy is influenced by CD4 level. No differences
in risk of death, toxoplasmosis and bacterial infections were observed between
the two regimens.
[22182 The role of aerosolized pentamidine prophylaxis in the
era of combination anti-retroviral therapy
Charles Chan1, Leslie Lee-Pack2, R. Palmer3, C.K.N. Chan2. 1200 Elizabeth St.
10EN220, Toronto, Ontario; 2The Toronto Hospital; 3Sunnybrook Hospital HIV
Project Center, Canada
Objective: To demonstrate the effectiveness of aerosolized pentamidine (AP) vs
systemic prophylaxis for Pneumocystis Carinii Pneumonia (PCP) in the era of
combination anti-retroviral therapy.
Methods: Retrospective analysis of a population of 1,900+ HIV positive individuals, enrolled in a government funded free AP program in Toronto, Canada.
Patients were enrolled with CD4 level <300 cell/mm3 and intolerant or failed
systemic prophylaxis. Longitudinal follow-up of all patients (1989-97) from time of
enrollment to either death or breakthrough PCP (BPCP) was implemented. Only
patients who have been on AP for greater than one year from enrollment were
included in this analysis. This inclusion criteria was used to eliminate patients
who may have been non-compliant or intolerant to AP, and also those patients
who may have a sub-clinical or smoldering PCP at their time of enrollment, i.e.
early BPCP.
Results:
Year 1989 1990 1991 1992 1993 1994 1995 1996
V 605 471 294 150 123 116 119 63
3PCP 105 72 35 18 12 8 3 1
% 17.4 15.3 11.9 12.0 9.8 6.9 2.5 1.6
X2L = 35.37, p-value <0.0005 BPCP rates are on patients on AP for greater than 12 months
from time of enrollment and CD4 at enrollment.
Conclusion: AP prophylaxis has become less popular as a PCP prophylaxis
regimen over the last 8 years. But the actual rate of BPCP episodes while on
AP has significantly dropped over the same period. With PCP being an important
opportunistic infection in AIDS, and the high intolerance to or drug interaction with
systemic prophylaxis, AP remains a good, safe and proven effective prophylaxis
regimen especially in the era of combination anti-retroviral therapy.
22183 Risk factors for pneumocystis carinii pneumonia in the
US
Jeffrey Duchin1, P. Simon2, T.M. Hooton3, S.G. Hopkins4, B.H. Sohlberg4,
S.E. Buskin4, J.L. Jones2. 1400 Yesler Way 3rd. Floor Seattle, WA 98104;

2Center for Disease Control, Los Angeles, CA; 3University of Washington,
Seattle, WA; 4Seattle-King County, Dept. of Public Health, Seattle, WA, USA
Background: Despite the availability of effective prophylaxis, Pneumocystis
carinii pneumonia (PCP) remains the most common opportunistic illness in HIVinfected persons.
Methods: Since February 1996, we have conducted a prospective case-control study of laboratory-confirmed cases of PCP at 8 hospitals in Seattle and Los