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

92 Abstracts 12392-12396

12th World AIDS Conference

anti-retroviral treatment. Facial atrophy was not observed in the 8 patients who
had received indinavir for less than 3 months, nor in the 7 patients who were
treated with other protease inhibitors (ritonavir, saquinavir, nelfinavir).
Conclusion: Facial atrophy is a frequent and often distressing condition affecting 24% of our patients receiving indinavir for more than 3 months. The basis
of this phenomenon is unknown and no predisposing factor other than treatment
with indinavir was identified.
S12392 The incidence and severity of diarrhea in HIV+ patients
from a large, urban medical center who have taken
nelfinavir in the past twelve months
Janet M. Kosmynal, R.D. MacArthur2. 14201 St. Antoine UHC-7C, Detroit,
Michigan 48201; 2Wayne State University, Detroit, MI, USA
Objectives: To determine the number of patients from a large urban medical
center population who reported diarrhea while on the protease inhibitor nelfinavir
(NFV) and to evaluate the severity and treatment of the diarrhea.
Design: Retrospective chart review with data abstraction.
Methods: We performed a database search of the 1000 HIV+ patients followed
at the Detroit Medical Center to find all patients who had taken NFV in the past
year. 181 patients who had taken NFV had evaluable data. Grading of diarrhea
was done as follows: Grade 1 (mild or transient diarrhea) up to 4 stools/day;
Grade 2 (moderate) 5-7 loose stools/day; Grade 3 (severe) >7 loose stools/day
or requiring intravenous (IV) hydration due to the diarrhea.
Results: 63/181 (35%) of patients reported diarrhea. Of these, 16 (25%) had
diarrhea prior to beginning NFV. 26 (41%) had grade 1 diarrhea, 22 (35%) had
grade 2 diarrhea, 8 (13%) had grade 3 diarrhea, 7 (11%) reported diarrhea, but a
grade could not be determined. Treatment for diarrhea was as follows: 28 (44%)
of patients received no therapy; 9 (14%) received over the counter therapy (OTC);
17 (27%) received prescription (Rx) anti-motility drugs; 2 received a combination
of Rx and OTC therapy; 3 received IV therapy alone or in combination with
other therapies; and in 4 patients, it is unclear whether any therapy was initiated
for diarrhea. Only 3 patients permanently discontinued NFV due to diarrhea.
The median CD4+ cell count and viral load of our patient sample was 168/tL
(range 0-1156/uIL) and 50,000/ml (range <200->750,000/ml), respectively, at
initiation of therapy. Patients with diarrhea had a median CD4+ cell count of 77/pL
(range 0-915/i/L) and median viral load of 72,500/ml (range <200->750,000/ml),
respectively, at initiation of therapy.
Conclusions: Severe or dose limiting diarrhea appears to be uncommon in
patients taking nelfinavir. Mild to moderate diarrhea is found in slightly greater
than one third of patients and can be controlled by the use of anti-motility drugs.
Patients with lower CD4+ cell counts and/or higher viral loads may be more likely
to experience diarrhea after the initiation of nelfinavir.
S12393 Safety profile of Viracept in the treatment of HIV patients:
The French compassionate use program experience
Christine Delmas', D. Szafir', A. Trylesinski2, M. Andriamanamihaja2,
P. Correia2, E. Dohin2, J.M. Goers2. 1Drug Safety, Products Roche France-52
BD Du Parc, 92521 Neuilly, Surseine; 2Clinical Department Roche France,
Neuilly, France
Objective: Assess the safety of Viracept~ in patients (pts) included in the French
compassionate program (ATU) since Apr 97.
Patients and Methods: Inclusion criteria were: intolerance or contra-indication
to the 3 registered protease inhibitors or therapy failure to indinavir or ritonavir
(therapy failure was defined by a viral load (VL) >50000 copies/mL and CD4
cell count <200/mm3). Viracept~ was given at 750 mg t.i.d. in combination with
at least 1 nucleoside analogue. In Oct. 97, the French Drug Agency expanded
the criteria to all adults HIV + and allowed Viracept~ in combination with any
antiretroviral drugs.
Results: From Apr. 97 to Jan. 98, 3312 pts were included. Mean duration of previous therapy was 3.4 years. Viracept~ was prescribed by 620 physicians in 200
hospitals. Viracept" was added to on going therapy in 44.5% pts and given as part
of a triple-therapy regimen in 91.5% pts. During 1st period (Apr.97-Oct.97) 1279
pts were included: 65% were at stage C (CDC classification), mean CD4 cell count
was 108/mm3 and mean VL was 5 log~o. During the 2nd period (Oct.97-Jan.98),
2033 pts were included, 180 were naive to antiretroviral therapy. 40% were at
stage C, mean CD4 cell count was 263/mm3 and mean VL was 4.21og0o. (In the
1st period, 144 out of 1279 pts presented an adverse event (AE). In 119 pts (9%)
Viracept~ was suspected as related by the investigators. In the 2nd period, 135
out of 2033 pts presented an AE. In 103 pts (5%). Viracept~ was suspected as
related. On the ATU overall, Viracept~ was discontinued in 123 out of 3312 pts
due to: AE: 49, treatment failure: 38, death (without AE): 8 and miscelaneous
reasons: 28. In 3% of the pts, AE were considered as likely or possibly related to
Viracept". The most frequent AE were: digestive disorders in 5% (diarrhoea in
3%), rash in 2%, neutropenia in 0.4%, abnormal liver function tests in 0.2%, and
endocrine disorders in 0.2%. According to the French seriousness criteria, 0.7%
of all the pts presented a serious AE (2 fatal outcome).

Conclusions: Even evaluated in this immunocompromised cohort concerning
3312 pts, Viracept~ had a favorable safety profile. About 1% of the pts stopped
their treatment because of AE. 0.7% of the pts presented a serious AE. The
most frequent AE were diarrhoea and rash. Few patients presented abnormal
biological tests.

123941 Evaluation of urinary pH and specific gravity in the
development of indinavir induced renal stones
John Gerber, S. Johnson. Univ Colorado Health Sciences Center, 4200 East 9th
Avenue Box C237 Denver Colorado 80262, USA
Objectives: To assess the relationship between urinary pH and urine concentration, and the development of indinavir-induced nephrolithiasis.
Design: Retrospective chart review of of medical records from a Universitybased HIV/AIDS Clinic to identify subjects with indinavir-induced nephrolithiasis
and to compare to subjects on indinavir for at least 6 months without complications.
Methods: We identified 13 patients in the HIV clinic who had developed urinary
complications associated with indinavir usage. For each case, clinical characteristics, results of diagnostic tests, and results of urinalysis, including urine pH
and concentration, were recorded using a standardized data collection form. A
comparison group consisted of 14 asymptomatic patients attending the clinic who
had been on indinavir for at least 6 months without apparent complications. A
urinalysis was performed on these patients. Data on urine pH and specific gravity
between the two groups were compared using an unpaired Student's t test.
Results: All patients with probable indinavir-induced nephrolithiasis had acute
flank pain and hematuria. None of them had previous history of GU abnormalities.
Most patients had either IVP, abdominal CT, or KUB confirmed obstruction. Several
patients reported passing stone material. Stone analysis in one patient confirmed
indinavir as the cause. The urinary pH of subjects with indinavir nephrolithiasis
was 6.4 ~ 0.2, while the urinary pH of those without this complication was 5.6 ~
0.1 (p = 0.01). Eight of the 13 patients with nephrolithiasis had a urine pH > 6,
compared to only 3 of 14 subjects without this complication (p = 0.05, Fisher's
Exact Test). The specific gravity was not different between the two groups (1.016
~ 0.001 without stones, and 1.019 ~ 0.002 with stones).
Conclusions: Our data suggest that patients with a higher urinary pH may be
more likely to develop indinavir-induced nephrolithiasis. Since indinavir's aqueous solubility decreases 10-fold when pH increases from 5 to 6, developing
dietary guidelines that result in lower urinary pH may be helpful in avoiding this
complication. This hypothesis requires a prospective study.
S12395 1 Evaluation of protease inhibitor-associated
hyperglycemia in a university-based HIV clinic
Richard Caldwell, A. Rothstein, C. Allmon, J.G. Montoya, A. Zolopa. Stanford
University Medical Center, 300 Pasteur Drive, Stanford, CA, USA
Objectives: To determine the incidence of hyperglycemia associated with protease inhibitors in a clinical practice setting.
Design: Retrospective, case review study
Methods: To determine the magnitude of this adverse effect, all medical records
of a university-based HIV clinic were reviewed for use of protease inhibitors, effects on serum glucose at various points during therapy and other potential
concomitant factors.
Results: A total of 307 patients were evaluated with 216 patients receiving at
least one protease inhibitor. There were 396 episodes of use of protease inhibitor
in these 216 patients. Protease inhibitor-associated hyperglycemia was seen in
25 of the 216 (11.5%) patients and in 31 of the 396 (7.8%) episodes of protease
inhibitor use. In the 25 patients who developed hyperglycemia, the median serum
glucose was 86.5 mg/dl prior to the initiation of the protease inhibitor and the
median serum glucose was 138.6 mg/dl after therapy began. Of the 31 episodes,
61% had at least one concomitant medication that has been associated with
hyperglycemia. The prevalence of hyperglycemia associated with indinavir was
11.6%, with saquinavir 4.3%, with nelfinavir 8.2% and with saquinavir/ritonavir
combination 6.3%.
Conclusion: Hyperglycemia is a prevalent side effect in some patients receiving protease inhibitors and warrants routine monitoring of serum glucose.
Hyperglycemia was seen in regimens containing all four currently licensed medications.
S112396 Managing the indinavir/nevirapine interaction via US
prescriber education on dosing strategies
Sarah Lewis, Lidia Gajewski, A. Ho-Kean, G.Y. Vanscoy. Stadtlanders Managed
Pharmacy Services, 600 Penn Center Boulevard Pittsburgh PA 15235, USA
Issue: Determination of the effectiveness of a nationwide prescriber-targeted
educational process directed at optimizing indinavir dosing in combination with
nevirapine.
Project: HIV/AIDS patients who are candidates for indinavir therapy must be
initiated and maintained on optimal doses of indinavir to delay emergence of resistant viral strains. However, when nevirapine is prescribed in combination with
indinavir, the dose of indinavir is increased to compensate for nevirapine's liver
enzyme induction. The need for a consistent and efficient mechanism for pharmacist management of the indinavir-nevirapine drug interaction was identified.
A proactive prescriber-targeted educational process was developed to address
this need. All prescriptions, received by the US's largest specialty HIV/AIDS

pharmacy, for indinavir doses that were outside of suggested guidelines were
identified by pharmacists and forwarded to a clinical pharmacy specialist for further assessment of the patient and dose appropriateness. Information addressing
indinavir dosing, in combination with nevirapine, and viral resistance was sent
to the physician in reference to each sub-optimal case. A physician action form
was enclosed which requested justification or modification of the current indinavir