 |
|
|
| |
Abacavir+3TC: Changes in ALT/AST in Coinfected
|
| |
| |
"Safety of Abacavir (ABC)+Lamivudine (3TC)-based HAART in ART-Naive HIV-Infected Subjects With and Without Hepatitis B (HBV) and/or Hepatitis C (HCV) Co-Infection"
This is an analysis of ALT/AST elevations in 4 trials of abacavir plus 3TC in combination with efavirenz or a protease inhibitor. This analysis looked at the treatment emergence of grade 2-4 ALT/AST. Patients with grade 3-4 ALT/AST were excluded from these studies & baseline median ALT/AST were within normal range. Treatment emergent grade 2-4 ALT/AST elevations were 8-10% for HBV or HCV coinfected vs 1.3% for non-coinfected. Considering that EFV or a PI was also used the results of this analysis suggest that ABC+3TC appear relatively safe regarding the risk for hepatotoxicity in coinfected patients. It would be helpful to see ALT/AST changes in patients with above normal ALT/AST before treatment is started.
Reported by Jules Levin
3rd IAS Conference
July 24-27, 2005
Rio de Janeiro
Poster Number TuPe1.1C16
Henry Zhao1, Jaime Hernandez1, Amy Cutrell1, Naomi Givens2, John Wakeford1 and Trevor Scott1
1GlaxoSmithKline R&D, RTP, NC, USA and 2Greenford, UK
INTRODUCTION
The interactions between hepatitis viruses and HIV are complex and clinically important. Co-infection with HIV accelerates HCV-related liver damage and progression to end stage liver disease. Similarly, HBV DNA levels are higher in HIV-infected patients and HIV may increase the risk of HBV-associated morbidity and mortality. Although antiretroviral therapy (ART) is beneficial for HBV and/or HCV co-infected subjects, hepatitis increases their risk for ART-associated hepatotoxicity.
A fixed dose combination (FDC) tablet of two antiretrovirals, abacavir (Ziagen, ABC) and lamivudine (Epivir, 3TC) was developed to reduce pill burden and dosing frequency. This improved dosing convenience may lead to improved adherence and potentially better clinical outcomes. The efficacy and tolerability of ABC + 3TC have been previously demonstrated in ART-naive subjects.1, 2 The objective of the analyses described here was to assess the safety and tolerability over 48 weeks of treatment with ABC + 3TC based HAART in HIV-1 infected ART naive adults with and without HBV and/or HCV co-infection.
METHODS
Data from 1985 ART-naive, HIV-infected subjects participating in 4 large, randomized clinical trials using ABC+3TC once daily (QD) or twice daily (BID) in combination with EFV or protease inhibitors (PI) were used for this analysis.
Subjects with co-infection were allowed to enroll in these 4 trials if their infection was not clinically relevant within the last 6 months, and if ALT and AST levels were below a Grade 3 (<5 x ULN) within 28 days of screening.
Safety data over >48 weeks of ART for patients with HBV (baseline positive HBV-SAg) and/or HCV (baseline positive anti-HCV) coinfection were compared to those of subjects without co-infection using meta-analysis method. Descriptive statistics were summarized for subjects with and without HBV and/or HCV co-infection.
RESULTS
The percentage of subjects with HBV and/or HCV co-infection was 15 to 25% in these 4 large clinical trials using ABC+3TC. Of 1985 subjects participating, 389 (20%) were HBV and/or HCV co-infected. Baseline demographics and disease characteristics were comparable between subjects with and without (1596 subjects) HBV/HCV co-infection.
The median number of days of exposure to ABC + 3TC in these 4 clinical trials was 337 to 421 days for non co-infected subjects compared to 321 to 428 days for co-infected subjects. 75 to 81% of non co-infected subjects participating in these 4 clinical trials received at least 24 weeks of ABC + 3TC therapy, compared with 68 to 80% of co-infected patients.
The Baseline ALT/AST values, the changes from BL in AST and ALT and the proportion of patients developing Grade 2-4 AST and ALT elevations for non co-infected and co-infected subjects are shown in
Tables 1 to 3.
As expected, median Baseline (BL) ALT and AST levels were higher
in co-infected subjects than in those without co-infection (Table 1).
The number of subjects with Grade 2-4 ALT or AST elevations
through 48 weeks of therapy was small (Table 3):
--41 co-infected subjects experienced a new treatment-emergent
Grade 2-4 ALT elevation through 48 weeks of ART.
--33 co-infected subjects experienced a new treatment-emergent
Grade 2-4 AST elevation through 48 weeks of ART.
Ed note: the analysis does not separate emerging grade 2 and grade 3-4 (>5 ULN).
Table 4. Adverse Events
The overall incidence of Adverse Events (AEs) was similar between
the two groups with 95% (1524/1596) and 90% (352/389) for subjects
without co-infection and with co-infection, respectively.
ED NOTE: the analysis does not report liver-related adverse events.
Through 48 weeks of ART, similar proportions of co-infected subjects
and non co-infected subjects reported grade 2-4 AEs and drug related
AEs (Table 4).
Table 5. AEs for Co-infected Subjects (CNA30021)
The incidence of specific AEs in co-infected subjects was comparable
between subjects taking ABC once daily (OAD) and those taking ABC
twice daily (BID).
|
|
| |
|
|
|
|
|
