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Early 12-Week Viral Response in HCV/HIV Coinfection Predicts Sustained Viral Response (SVR) in APRICOT Study
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Reported by Jules Levin
88% of genotype 2/3 show early virologic response at week 12, 63% of genotype 1 show early virologic response at week 12
"Early prediction of sustained virological response during treatment with peginterferon alfa-2a (40kd) (PEGASYS) plus ribavirin (COPEGUS) in patients with HIV/HCV co-infection: results from the AIDS PEGASYS Ribavirin International Co-infection Trial (APRICOT)"
authors: M Rodriguez-Torres, FJ Torriani, E Lissen, N Brau, R Sola, C Tural, N Clumeck, D Cooper, DT Dieterich
Potent antiretroviral therapy has reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. As a result, the pattern of morbidity and mortality in this population has shifted and physicians are now frequently confronted with the complications of hepatitis C virus (HCV) co-infection. Thus, effective treatment for HCV infection in HIV-co-infected patients has become a priority.
Treatment for 48 weeks with the combination of pegylated interferon plus ribavirin produces overall sustained virological response (SVR) rates of 52% to 63% in HCV-mono-infected patients with chronic hepatitis C, and is recognized as the current treatment of choice.
The results of the AIDS PEGASYS Ribavirin International Co-Infection Trial (APRICOT) demonstrate that the benefits of peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) therapy extend to patients with HIV-HCV co-infection: overall 40% of patients treated with this combination for 48 weeks achieved an SVR (vs 12% of patients treated with interferon/ribavirin, p<0.0001). Patients randomized in APRICOT to Pegasys mono-therapy had an SVR of 20%.
Patients were randomized in APRICOT to 48 weeks of treatment with one of three regimens:
--Peginterferon alfa-2a (40KD) 180 µg/week plus ribavirin 800 mg/day
--Peginterferon alfa-2a (40KD) 180 µg/week plus placebo
--Interferon alfa-2a 3 MIU 3 times per week plus ribavirin 800 mg/day
Following the 48-week treatment period, patients were followed for an additional 24 weeks.
SVR was defined as undetectable HCV RNA by qualitative polymerase chain reaction (PCR) (<50 IU/mL COBAS AMPLICOR HCV Test v. 2.0) at the end of untreated follow-up (week 72)
Early virological response was defined as undetectable HCV RNA by qualitative PCR or a >=2-log10 decline in HCV RNA by quantitative PCR (COBAS AMPLICOR HCV MONITOR Test v. 20, limit of detection 600 IU/mL) week 12.
This analysis is based on data from patients treated with peginterferon alfa-2a (40KD) plus ribavirin.
The ability to identify patients most likely to achieve an SVR allows those individuals to be targeted for a complete course of therapy and minimizes the overall costs of treatment and the likelihood of adverse events in those unlikely to achieve an SVR. In HCV mono-infected patients treated with peginterferon alfa-2a plus ribavirin, the absence of an early virological response (defined as a minimum 2-log10 reduction in viral load by week 12 of therapy) has a high negative predictive value (NPV) regarding the likelihood of achieving an SVR.
The presence or absence of an early virological response may be used to guide treatment decisions about continuation or cessation of therapy in patients infected with HCV genotype 1. It has not beenknown whether the week 12 predictability criterion applies in HIV-HCV co-infected patients.
The aim of this study was to determine the predictive value of an early virological response on the probability of achieving an SVR in HIV-HCV co-infected patients treated with peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) in the APRICOT study.
SUMMARY:
In HIV-HCV co-infected patients, treatment for 48 weeks with the combination of peginterferon alfa-2a (40KD) (PEGASYS) 180 µg/week plus ribavirin (COPEGUS) 800 mg/day results in an overall SVR rate of 40% (116/289), and SVR rates of 29% (51/176) and 62% (59/95) in patients infected with HCV genotypes 1, and 2/3, respectively.
In the absence of an early virological response (minimum 2-log10 decrease in HCV RNA) at week 12 it is highly unlikely that a patient will achieve an SVR at the end of follow-up (NPV=98%). The predictive value was similar at week 24. Thus, if SVR is the only goal of therapy, treatment could be stopped in patients without an early virological response at week 12 in order to preserve health care resources and prevent adverse events. It must be noted that antiviral therapy for HCV may produce histological improvement and retard disease progression in HIV-HCV co-infection, factors which must be considered when making treatment decisions.
Patients with an early virological response have a good chance of achieving an SVR. These results are consistent with those obtained in HCV mono-infected patients, and suggest that the 12-week predictability algorithm may be extended to patients with HIV-HCV co-infection.
DETAILED RESULTS
Patients with an early virological response at week 12 were more likely to achieve an SVR than those without an early virological response. At week 12, 204 of 289 (71%) patients had an early virological response, of whom 114 (56%) achieved an SVR. Conversely, only 2 of 85 patients without an early virological response at week 12 achieved SVRs. So the Positive Predictive Value (PPV) was 56% and the Negative Predictive Value (NPV) was 94%.
Similar results were obtained when virological response data at week 24 were considered. At week 24, 216 of 289 (75%) of patients had an early virologic response, of whom 115 (53%) achieved an SVR; so the PPV is 53%. Only 1 patient of 73 without an early virologic response at week 24 achieved an SVR, for a NPV of 99%.
When the data are grouped by HCV genotype, the trends present in the overall results were retained. Of the 176 patients with genotype 1, 110 (63%) had an early virologic response at week 12, and 50 of the 110 patients (45%) had an SVR, for a PPV of 45%. Only 1 patient of 66 without an early virologic response at week 12 achieved an SVR, for a NPV of 98%. Of the 95 patients with genotype 2 or 3, 84 patients (88%) had an early virologic response at week 12, for a PPV of 70%. None of the 11 patients without an early response week 12 achieved an SVR, for a NPV of 100.
Although it's just a trend and the study authors did not mention this in the poster, the PPV of genotype 2/3 was 70% compared to the PPV for genotype 1 which was 45%. 88% of genotype 2/3 patients achieved an early viral response at week 12 compared to 63% for genotype 1 patients.
BASELINE DEMOGRAPHIC AND VIROLOGIC CHARACTERISTICS OF 289 PATIENTS TREATED WITH PEGASYS PLUS RBV
Male: 80%
Age: 39 yrs
Weight: 72 kg
Body Mass Index: 24 kg/m2
Race: 80% white, 11% black, 9% other
Serum HCV RNA: 5.6 million IU/mL
HCV RNA >800,000 IU/mL: 72%
HCV genotype: 61% G1, 33% G2/3
CD4 count: 520
HIV RNA: 2.3 log copies/ml
Patients with undetectable HIV RNA (<50 copies/ml): 60%
Patients' Study Elgibility
Patients eligible for enrollment in the APRICOT study were HCV RNA and HCV antibody positive, had elevated serum alanine aminotransferase (ALT) levels documented on two occasions within the previous 12 months, and had HIV-1 disease confirmed by detectable anti-HIV-1 antibodies or HIV-1 RNA in serum. Participants had compensated liver disease, a CD4+cell count 3100 cells/µL and stable HIV disease. Patients were excluded if they had previously received interferon or ribavirin.
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