icon- folder.gif   Conference Reports for NATAP  
 
  4th IAS (Intl AIDS Society) Conference on HIV Pathogenesis, Treatment and Prevention
Sydney, Australia
22-25 July 2007
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Treatment Simplification to an Atazanavir-Containing Regimen: Impact on Patients' Perception of Symptom Severity
 
 
  Reported by Jules Levin
4th IAS Conference, July 22-25, 2007, Sydney, Australia
 
J. Gatell1, G. L'Italien2, V. Wirtz2, L. Odeshoo2 and I. Villanueva3 1Clinical Institute of Medicine & Dermatology, Infectious Diseases & AIDS Units, Barcelona, Spain; 2Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut, United States; and 3Bristol-Myers Squibb, Research and Development, Braine-l'Alleud, Belgium
 
Antiretroviral agents used in the treatment of HIV disease are associated with a wide range of symptoms of varying severity. Drug related symptoms may impact both adherence to regimen and patients' perception of tolerability with the regimen. We assessed the frequency of patient reported symptoms with their HAART regimen among patients enrolled in a randomized clinical trial.
 
Author Conclusion:
Following treatment simplification to an ATV-containing regimen, patients receiving ATV reported fewer GI, well being, and certain lipodystrophic side symptoms than patients receiving the original PI based regimen. No attempt was made to match or reconcile questionnaire symptoms with adverse events reported for the study
 
Limitation:
As for any open label study, patient reporting may by biased in favor of the newer (i.e., the experimental) regimen
 
METHODS
 
Figure 1: Study Design
 
Current ARV Regimen*
Screening Criteria

Stable PI-containing regimen (HIV RNA <50 copies/mL for ³3 months prior to screening, CD4 count
> 50 cells/mm3)
-- PI +/- RTV
-- First or second HAART treatment
No previous virologic failure while on PI-based HAART
Current PI component dosed at least BID and/or ³ 3 pills/day
 
2:1 Randomization
Stratified by RTV Boosting Use in Prior Regimen at Screening
 

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ABSTRACT
Background: Patients' perception of convenience of HAART therapy can be influenced by dosing frequency, pill burden, and tolerance. These factors contribute to non adherence and treatment failure. This study evaluated patients' perception of tolerance of HAART-related symptoms in patients switched to atazanavir (ATV)
 
Methods: BMS097 (SWAN) was a Phase IIIb, 48 week, multicenter, open-label, randomized, prospective trial, comparing the efficacy and safety of switching to an ATV-containing regimen versus continuing an unmodified ARV regimen (comparator PI, CPI) in patients on stable PI +/- ritonavir (RTV)-containing HAART with no previous PI virologic failure. Patients' self-report of the severity of HAART-related side symptoms was assessed using the Symptom and Side Effect Severity Questionnaire (SSESQ). Proportions with symptoms across all levels of perceived severity were reported for all study time points by regimen
 
Results: A total of 407 patients were enrolled in the study (274 ATV and 133 CPI). Higher rates of GI symptoms (ie, diarrhea) were reported in the CPI versus the ATV regimen at 4 weeks (63% vs 16%), 12 weeks (58% vs 16%), 24 weeks (57% vs 19%), 36 weeks (53% vs 16%) and 48 weeks (51% vs 15%). Other symptoms more frequently reported in CPI vs ATV were abdominal pain, abdominal girth, weakness, muscle aches, dry skin, joint pain, thirst, numbness in hands or feet, face, arms and legs becoming thinner. The other most frequently reported events were evenly distributed between treatment arms during follow-up
 
Conclusions: Following treatment simplification to an ATV-containing regimen, patients receiving ATV reported fewer GI, certain well being, and certain lipodystrophic symptoms than patients receiving the original PI based regimen.
 
Table 2: SSESQ: Proportion of Subjects Who Experienced Mild to Severe Symptoms from Baseline to 48 Weeks - Treated Subjects - Most Frequently Reported Symptoms (>20%)
Those symptoms reported with consistently greater frequency over the entire follow-up period for CPI vs ATV were diarrhea, abdominal pain, abdominal girth, weakness, muscle aches, dry skin, joint pain, thirst, numbness in hands or feet, face, arms and legs becoming thinner. The other most frequently reported symptoms were evenly distributed between treatment arms during follow-up.
 

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METHODS
 
BMS097 (SWAN) was a Phase IIIb, 48 week, multicenter, open-label, randomized, prospective trial, comparing the efficacy and safety of switching to an ATV-containing regimen versus continuing unmodified anti-retroviral (ARV) regimen (comparator PI, CPI) in patients on stable PI+/- ritonavir (RTV)-containing HAART with no previous PI virologic failure
 
Male or female HIV-infected subjects aged 18 years and older who were on a stable PI-containing regimen (RTV boosted or not, first or second HAART treatment) and who had a suppressed viral load (< 50 c/mL) for at least 3 months before screening, a CD4 count > 50 cells/mm3, and no known history of virologic rebound while on PI therapy were eligible for the study
 
Subjects were randomized in a 2:1 ratio to 1 of the 2 study arms: an ATV-containing regimen or their current regimen without ATV
 
The primary objective for the SWAN study was to compare the proportion of subjects with virologic rebound above the LLQ of 50 c/mL at or prior to 48 weeks of follow-up between subjects who switch to an ATV-containing regimen and those who remain on their current regimen without ATV
 
Patient self reported symptom severity was assessed using the Symptom and Side Effects Severity Questionnaire (SSESQ). The SSESQ assessed the subjects' perceived severity of a particular symptom during the last 4 weeks at each visit. No attempt was made to match or reconcile questionnaire events with adverse events reported on the CRF. The format of the answers is categorical ranging from "absent" to "severe". The answers to each of the 41 items are recoded into a 0 to 3 score system (ie, Absent = 0; Mild= 1; Moderate = 2; and Severe = 3). No formal statistical tests were applied to compare the proportion of subjects who reported AEs across all levels of severity
 
The following proportions were tabulated by treatment regimen at each time point for each question:
--Subjects who reported at least 1 mild, moderate, or severe sign/symptom
--Subjects who reported at least 1 mild sign/symptom
--Subjects who reported at least 1 moderate sign/symptom
--Subjects who reported at least 1 severe sign/symptom
 
No formal statistical tests of the SSESQ results were performed comparing treatment arms. Proportions of patients reporting symptoms across all levels of perceived severity were reported for all study time points by treatment regimen
 

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Percentages are based on subjects with measurements (AIDS include all treated subjects).
 
A total of 407 patients were treated (274 ATV and 133 CPI). The demographic and baseline disease characteristics were comparable for the ATV and comparator PI treatment regimens. The overall mean times on PI, NRTI and NNRTI for randomized subjects prior to baseline were 175, 202, and 70 weeks, respectively. Thirty-one percent of treated subjects were co-infected with the hepatitis B and/or hepatitic C virus at baseline
 
SSESQ results are summarized in Table 2 for the most frequently (>20%) reported (at baseline) symptoms (18/41)