The first study was a retrospective
analysis of participants in the GESIDA 50/06 study comparing the effectiveness
and safety of pegylated interferon plus ribavirin in HIV-HCV coinfected patients
taking a HAART regimen that
included tenofovir versus those not using tenofovir.
•
Tenofovir group (n = 238): those whose NRTI
backbone consisted of tenofovir + 3TC (lamivudine; Epivir) or emtricitabine
(Emtriva);
•
Non-tenofovir group (n = 481): patients whose
NRTI components were AZT + 3TC (n =265), d4T + 3TC (n = 164), or abacavir + 3TC
(n =52).
The
primary efficacy endpoint was sustained virological response to pegylated interferon/ribavirin.
Results
•
Patients in the tenofovir and non-tenofovir
groups were well matched on baseline characteristics, except for a lower mean
CD4 cell count, exposure to more HAART regimens, and a higher mean AST/ALT quotient.
•
Safety analysis revealed no differences between
the groups in relation to death, hepatic decompensation, or interruption of pegylated
interferon/ribavirin due to adverse events.
•
Ribavirin dose reduction was more frequent
in the non-tenofovir group (13% vs 20%), particularly among patients treated with
AZT (23%).
•
No significant differences were observed in
SVR rates among patients in the tenofovir and non-tenofovir groups by intent-to-treat
(ITT) analysis (45% vs 39%).
•
Factors associated with SVR in a univariate
analysis were HCV genotype 2
or 3, HCV viral load < 500,000 IU/mL, baseline HIV viral load < 50 copies/mL,
AST/ALT quotient, and alcohol intake > 50 g/day.
•
When adjusted for these variables, the odds
ratio (OR) of achieving SVR in the different dual-NRTI groups by logistic regression
is shown in the table below.
Group
OR
of SVR
95%
CI
P value
Tenofovir
+ 3TC or emtricitabine
1.70
(1.05
to 2.77)
0.03
AZT
+ 3TC (including AZT/3TC/abacavir)
0.60
(0.37
to 0.99)
0.05
d4T
+ 3TC
1.09
(0.65
to 1.82)
0.73
Abacavir
+ 3TC
0.80
(0.32
to 2.08)
0.68
Based on these
findings, the authors concluded, "Our results suggest that in HIV-HCV [coinfected]
patients, the use of tenofovir DF + 3TC or [emtricitabine] is associated with
an improved response to pegylated interferon/ribavirin."
Conversely,
they added, "the concomitant use of AZT and pegylated interferon/ribavirin
is associated with a worse tolerability and effectiveness."
The 40%
lower SVR rate for patients using AZT was likely attributable to a greater likelihood
of adverse events such as anemia. Current
HIV-HCV coinfection guidelines recommend that patients taking ribavirin should,
if possible, avoid AZT.
Negative
Interaction between Ribavirin and Abacavir
The
second CROI 2008 study on this topic was presented by Jose Mira and colleagues,
also working at multiple medical centers in Spain.
The researchers noted
that recent studies have provided data showing that the use of abacavir along
with pegylated interferon/ribavirin
is associated with higher rates of non-response to hepatitis C therapy. However,
they observed that in most of these studies, abacavir was combined with AZT in
a substantial proportion of patients, which could act as a confounder.
Therefore,
the objective of their study was to compare the efficacy of pegylated interferon/ribavirin
among HIV-HCV coinfected patients
taking a NRTI backbone consisting of abacavir + 3TC versus that observed in those
taking tenofovir + 3TC or emtricitabine.
The investigators studied 256
patients starting first-line pegylated interferon/ribavirin while taking a 3-drug
antiretroviral regimen including 1 PI or 1 NNRTI and either abacavir + 3TC or
tenofovir + 3TC or emtricitabine as a NRTI backbone. SVR rates in both groups
were compared. Other potential predictors of sustained response were evaluated.
Results
•
In an ITT analysis, 20 of 70 individuals (29%)
receiving abacavir and 83 of 186 (45%) treated with tenofovir achieved SVR.
•
Using a NRTI backbone containing tenofovir
was an independent predictor of SVR in a multivariate analysis.
•
HCV genotype 2 or 3, baseline LDL cholesterol
> 100 mg/dL, lower baseline HCV RNA, and undetectable baseline HIV viral
load also predicted SVR.
•
The association between abacavir use and lower
SVR rate was mainly seen in patients with HCV RNA > 600,000 IU/mL, HCV genotype
1 or 4, and those who received a lower dose of ribavirin.
•
Among individuals treated with <13.2 mg/kg/day
ribavirin, 20% taking abacavir versus 52% taking tenofovir achieved SVR (P = 0.03).
•
Respective rates were 31% and 38% among those
receiving a ribavirin dose > 13.2 mg/kg (P = 0.4).
Based
on these results, the investigators concluded, "HIV-HCV coinfected patients
who receive abacavir + 3TC respond worse to pegylated interferon/ribavirin than
those who are given tenofovir + 3TC or [emtricitabine] as NRTI backbone."
In
addition, they wrote, "Differences between these NRTI combinations are chiefly
observed in subjects receiving lower ribavirin doses and in those who need higher
dosage of this drug.
Finally, they stated, "These findings suggest
a negative interaction between ribavirin and abacavir."
Better
Response to Hepatitis C Therapy in Coinfected Patients Taking Tenofovir (Viread),
but Worse with AZT (Retrovir) or Abacavir (Ziagen)
Results
