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Hepatitis C Viral Kinetics: Changes in HCV Viral Load during the First 2 Weeks Are Associated with Virologic Response but Are Not Affected by HIV Status
Mamta Jain*1, J Shelton1, A Reeck1, N Attar1, B Huet1, A Neumann2, M Gale1, and W Lee1
1Univ of Texas Southwestern Med Ctr, Dallas, US and 2Bar-Ilan Univ, Ramat-Gan, Israel
Background: HIV/hepatitis C virus (HCV) -co-infected
patients respond poorly to pegylated interferon (pegINF) + ribavirin (RBV)
therapy. We asked whether HIV infection affected first- or second-phase decline
to yield the poorer virologic responses (fewer sustained virologic responses)
generally observed with HIV. We compared viral kinetics in a prospective,
homogeneous cohort with and without HIV.
Methods: All patients received pegINF-α2a with
weight-based RBV. HCV viral load was measured using VERSANT 3.0 HCV RNA (bDNA)
at baseline, 24, 28, and 32 hours, then day 2, 3, 4, 7, 9, 11, 14, 21, 28, 42,
and 56 and 12 weeks. Sustained virologic
response and HIV status to baseline log HCV viral load, HCV viral load at day
2, first-phase decline, second-phase decline, and rebound HCV viral load at day
7 by the Wilcoxon rank sum test. Relationship between rebound at end of first
week and first-phase decline, second-phase, and day-2 viral load, and
second-phase slope and first-phase decline was examined with Spearman’s
correlations.
Results: We treated 15 HCV genotype
1 Caucasians (9 HIV+, 6 HIV–). Sustained
virological response was achieved in 5 (2 HIV+, 3 HIV–; 8
were non-responder/relapsers (5 HIV+, 3 HIV–), and 2 are
still on therapy. No differences were observed between HIV+ vs HIV–
for viral kinetic parameters, yet those who achieved sustained virologic response
had lower median baseline log HCV RNA (5.58 vs 6.13), p = 0.003. Rate of first phase decline was not associated with
sustained virologic response; second phase showed greater decline in those with
sustained virologic response (0.67 vs 0.24, p
= 0.06). However, the magnitude of
log HCV RNA decline between week 1 and 2 was larger with sustained virologic
response (0.67 vs 0.17, p = 0.003),
while rebound at day 7 was associated with non-response (–0.27 sustained
virologic response vs 0.48 non-responder, p
= 0.006). No correlation existed between rebound at end of first week and slope
of first phase. Second phase decline was faster in those with a lower HCV viral
load at day 2, r = –0.67, p = 0.009.
Conclusions: HIV status does not affect rate of first and
second phase viral decline. Lower baseline HCV viral load is associated with
response to HCV therapy. A faster second-phase decline occurred in those with a
faster first-phase and lower day-2 HCV viral load. Rebound of HCV viral load
after 1 week may indicate a lower likelihood of sustained virologic response.
Sustained virologic response was associated with better decline of HCV viral
load within the first 2 weeks of therapy. An early indicator of poor response
may be early rebound of HCV viral load at day 7. Lower response in HIV patients
may, in part, be due to higher baseline HCV viral load, but is not due to rate
of first- and second-phase decline.
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