Treatment of acute hepatitis C in human immunodeficiency virus–infected patients: The HEPAIG study†‡§
Potential conflict of interest: Dr. Piroth is a consultant for ROche and Schering-Plough. Dr. Duval is a consultant for, and received grants from GlaxoSmithKline and Gilead. He also received grants from Roche. Dr. Alric is a consultant for, and received grants from Schering-Plough, Roche, and Bristol-Myers Squibb. Dr. Pol is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche. He is also a consultant for, advises, and is on the speakers' bureau of Schering-Plough.
This work was done within the surveillance activities of the Institut de Veille Sanitaire, which is funded by the French Ministry of Health
The Steering Committee of the HEPAIG study also includes Yann Le Strat (Institut de Veille Sanitaire, Saint Maurice, France), Françoise Linard (Department of Infectious Diseases, Tenon University Hospital, Paris), Jean-Yves Le Talec (CERTOP SAGESSE UMR 5044, University of Toulouse II, Toulouse, France), and Annie Velter (Institut de Veille Sanitaire, Saint Maurice, France)
Abstract
Acute hepatitis C continues to be a concern in men who have sex with men (MSM), and its optimal management has yet to be established. In this study, the clinical, biological, and therapeutic data of 53 human immunodeficiency virus (HIV)-infected MSM included in a multicenter prospective study on acute hepatitis C in 2006-2007 were retrospectively collected and analyzed. The mean hepatitis C virus (HCV) viral load at diagnosis was 5.8 ± 1.1 log10 IU/mL (genotype 4, n = 28; genotype 1, n = 14, genotype 3, n = 7). The cumulative rates of spontaneous HCV clearance were 11.0% and 16.5% 3 and 6 months after diagnosis, respectively. Forty patients were treated, 38 of whom received pegylated interferon and ribavirin. The mean duration of HCV therapy was 39 ± 17 weeks (24 ± 4 weeks in 14 cases). On treatment, 18/36 (50.0%; 95% confidence interval 34.3-65.7) patients had undetectable HCV RNA at week 4 (RVR), and 32/39 (82.1%; 95 confidence interval 70.0-94.1) achieved sustained virological response (SVR). SVR did not correlate with pretreatment parameters, including HCV genotype, but correlated with RVR (predictive positive value of 94.4%) and with effective duration of HCV therapy (64.3% for 24 ± 4 weeks versus 92.0% for longer treatment; P = 0.03). Conclusion: The low rate of spontaneous clearance and the high SVR rates argue for early HCV therapy following diagnosis of acute hepatitis C in HIV-infected MSM. Pegylated interferon and ribavirin seem to be the best option. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of HCV genotype. (HEPATOLOGY 2010)
In the era of highly active antiretroviral therapy (HAART), acute hepatitis C remains a concern in human immunodeficiency virus (HIV)-infected patients. Increasing rates of hepatitis C virus (HCV) acquisition in HIV-infected patients, particularly in HIV-infected men who have sex with men (MSM), have been reported since 2001 in western European countries.1, 2 The accelerated course of liver disease and the lower rate of response to HCV therapy in HIV-infected patients who develop chronic hepatitis C underline the need for early diagnosis and better knowledge on the optimal management and treatment of acute hepatitis C.3
Most of the available data on the management and treatment of acute hepatitis C come from trials performed in HCV monoinfected patients.4 Several studies have nevertheless been conducted in HIV-infected patients.5 These studies suggest that the natural history and the response to therapy may be different in HIV-infected patients, even though the therapeutic schedules studied are often heterogeneous and the number of treated patients is small. However, large prospective cohorts and therapeutic trials, although needed in this population, are unlikely to be available soon. Clinical studies are thus still of interest, particularly when they focus on homogeneous populations and therapeutic schedules. The aim of the present study was to describe the clinical presentation, the spontaneous evolution, and the response to HCV therapy in acute hepatitis C in 53 MSM in France.
Abbreviations: ALT, alanine aminotransferase; CI, confidence interval; HAART, highly active antiretroviral therapy; HCV, hepatitis C virus; HIV, human immunodeficiency virus; MSM, men who have sex with men; PEG-IFN, pegylated interferon; RVR, rapid virological response; SVR, sustained virological response.
Patients and Methods
HEPAIG Study.
A prospective study (the HEPAIG Study) was conducted in 2006 and 2007 in France to assess the incidence of HCV among HIV-infected MSM and to better understand the transmission dynamics of HCV emergence in this population. This study first aimed to describe the clinical and epidemiological characteristics of acute hepatitis C virus (HCV) infection in HIV-infected MSM, and to estimate its incidence in France. A sampling frame of 115 medical wards was constituted according to the number of HIV and acquired immunodeficiency syndrome cases in MSM reported to the national HIV surveillance system between 2003 and 2005. Study questionnaires were completed by physicians for each patient meeting the case definition after obtaining consent. Data on the sociodemographic, clinical, and biological details; HCV and HIV infections; hepatitis B virus markers; and HCV risk factors prior to HCV diagnosis were collected prospectively. In 2008-2009, the 79 patients included in the HEPAIG Study were invited to participate in the present study, which aimed to describe the medical management and care of patients with acute hepatitis C.
Case Definition.
Acute HCV was defined as a positive anti-HCV antibody or a positive HCV polymerase chain reaction within 1 year of a documented negative anti-HCV test, or by the occurrence of positive HCV RNA associated with clinical and biological (elevated alanine aminotransferase [ALT] level) signs of hepatitis and negative anti-HCV antibody within 1 year of a regular and normal ALT level or within 1 year of documented negative HCV RNA. The maximal delay from HCV contamination was assumed to be <3 months in cases of clinical and biological signs of hepatitis, or as the interval of time between the last negative HCV serology or negative HCV RNA and the first positive one.
Data Collection.
Patients from the HEPAIG Study who agreed to participate in the present study and who provided a consent form were included. The treating physicians were asked to fill in a standardized questionnaire covering follow-up and management of the HCV infection. Information was collected regarding (1) the results of liver function tests, (2) the virological evolution of the HCV infection, (3) the underlying reasons for nontreatment in patients who were not treated for HCV, (4) the type of HCV therapy administered for others, and (5) the side effects and the supportive measures used to manage them.
Statistical Analysis.
A chi-square test or Fisher's exact test was used to analyze qualitative variables when appropriate, and a Mann-Whitney U test was used to compare the distribution of quantitative variables between groups. A survival analysis was used to assess the cumulative rate of spontaneous HCV clearance. Spontaneous clearance was defined as a confirmed negative result for HCV viral load in the absence of any specific anti-HCV therapy. Patients in whom no spontaneous clearance was observed were censored at the time HCV therapy was introduced or at the time of the last visit when untreated. For the percentages of virological response, 95% confidence intervals (CI) were calculated. For all tests, a P value <0.05 was considered significant.
Ethics.
This study complied with the ethical guidelines of the 1975 Declaration of Helsinki. Ethical approval was obtained from the French data protection authority. The purpose and the protocol of the study were explained to all patients, and informed consent was obtained from each participant.
Results
Patient Characteristics.
Of the 79 patients included in the HEPAIG Study (all of whom had proven acute hepatitis C in 2006-2007), 53 agreed to participate in the present study. The diagnostic criteria for acute hepatitis C were clinical and biological evidence of acute hepatitis C (n = 9; 17%), documented HCV seroconversion within 1 year (n = 22; 42%), positive HCV RNA and elevated ALT with negative HCV serology dating back <1 year (n = 11; 21%), or positive HCV RNA following negative HCV RNA dating back <1 year (n = 11; 21%). The maximal delay from HCV contamination to diagnosis of acute hepatitis C was <3 months in 31 cases and <1 year in 13 cases.
The patients included in the follow-up study did not differ from those who were not included (data not shown) in terms of age, HIV infection (CD4 count, Centers for Disease Control and Prevention clinical stage, treatment status), the presence of jaundice, concomitant sexually transmitted infections, the type of acute hepatitis C (acute symptomatic, seroconversion). Acute hepatitis C was diagnosed in these patients because of jaundice (n = 6) and/or other clinical symptoms (n = 13, mainly asthenia) and/or because of recent high-risk sexual intercourse (n = 15) and/or elevated ALT levels (n = 39). Mean (± SD) ALT elevation at diagnosis was 484 ± 67 IU/L (11.1 ± 1.8 times the upper limit of normal). Acute hepatitis C was associated with another sexually transmitted disease in 20 (38%) patients, primarily syphilis (n = 14). Three patients also had positive hepatitis B surface antigenemia. In one case, acute hepatitis C was concomitant with HIV primoinfection. The CD4 count was above 500/mm3 in 29 patients, between 350 and 500/mm3 in 14 patients, between 200 and 350/mm3 in eight patients, and below 200/mm3 in two patients. Antiretroviral therapy was ongoing in 42 (79.2%) patients, and 31 patients had an undetectable HIV viral load. Of the 49 patients with an available HCV genotype, 28 (57.1%) 14 (28.6%), and 7 (14.3%) were infected with HCV genotype 4, 1, and 3, respectively. The mean HCV viral load was 5.8 ± 1.1 log10 IU/mL at the time of acute hepatitis C diagnosis.
Follow-up.
Among the 53 patients in the present study, eight experienced spontaneous clearance. The mean delay between acute hepatitis C diagnosis and last negative HCV RNA in cases of spontaneous clearance was 25.9 ± 15.0 months. The cumulative rate of spontaneous HCV clearance was 8.3% 1 month after the diagnosis of acute HCV infection, 11.0% at 3 months, and 16.5% at 6 months. The only difference observed between the patients with spontaneous HCV clearance and those without was the HIV viral load (3.54 ± 1.97 versus 2.43 ± 1.30 log10 copies/mL; P = 0.05) at the diagnosis of acute hepatitis C. No other difference was observed, particularly regarding the CD4 strata (P = 0.41) or the HCV viral load (5.58 ± 1.87 versus 5.86 ± 0.90 log10 IU/mL; P = 0.54).
Overall, 13 patients were not treated for HCV. The characteristics of patients who were treated and those who were not are presented in Table 1. The main reasons for nontreatment were spontaneous HCV clearance before any treatment (n = 8), patient refusal (n = 3), priority given to the management of HIV infection (n = 1), and a too long delay since the onset of acute hepatitis C (n = 1).
| Untreated for HCV (n = 13) | Treated for HCV (n = 40) | PValue | |
|---|---|---|---|
| Age at diagnosis, years | 44.5 ± 6.7 | 40.5 ± 5.7 | 0.04 |
| Number of visits in the year preceding the diagnosis | 4.7 ± 2.6 | 5.0 ± 3.8 | 0.79 |
| Number of liver enzyme assessments in the year preceding the diagnosis | 3.9 ± 2.2 | 4.4 ± 2.4 | 0.53 |
| Diagnostic criteria for acute hepatitis C | 0.32 | ||
| Documented HCV seroconversion <1 year | 7 (54) | 15 (38) | |
| Positive HCV RNA and elevated ALT with negative HCV serology <1 year | 1 (8) | 10 (25) | |
| Positive HCV RNA with negative HCV RNA <1 year | 1 (8) | 10 (25) | |
| Clinical and biological evidence of acute hepatitis C | 4 (31) | 5 (12) | |
| Maximal delay since HCV contamination, months | 5.3 ± 4.2 | 5.8 ± 5.6 | 0.79 |
| Clinical symptoms at diagnosis | 4 (31) | 11 (28) | 1.00 |
| Associated sexually transmitted infections | 7 (54) | 13 (33) | 0.33 |
| Positive anti-HBc antibodies | 4/12 (33) | 24/33 (73) | 0.02 |
| Highly active antiretroviral therapy | 11 (85) | 31 (78) | 0.58 |
| CD4 count | 0.26 | ||
| ≥500/mm3 | 6 (46) | 23 (58) | |
| 350-499/mm3 | 6 (46) | 8 (20) | |
| 200-349/mm3 | 1 (8) | 7 (17) | |
| <200/mm3 | 0 (0) | 2 (5) | |
| HIV RNA, log10 copies/mL | 2.92 ± 1.76 | 2.50 ± 1.35 | 0.37 |
| HCV genotype | 0.38 | ||
| 4 | 7 (54) | 21 (51) | |
| 1 | 4 (31) | 10 (24) | |
| 3 | 0 (0) | 7 (17) | |
| HCV RNA, log10 UI/mL | 5.51 ± 1.47 | 5.92 ± 0.90 | 0.27 |
| ALT, ×ULN | 9.0 ± 8.4 | 12.0 ± 13.5 | 0.46 |
| AST, ×ULN | 7.7 ± 11.0 | 7.6 ± 9.1 | 0.98 |
| ALP, ×ULN | 1.1 ± 0.8 | 0.9 ± 0.3 | 0.41 |
| GGT, ×ULN | 4.7 ± 3.3 | 5.5 ± 4.9 | 0.62 |
| Total bilirubin, ×ULN | 2.1 ± 3.2 | 1.4 ± 2.1 | 0.47 |
| Prothrombin, % | 95.3 ± 8.5 | 90.0 ± 10.0 | 0.20 |
- Data are presented as the mean ± SD or n (%).
- Abbreviations: anti-HBc, antibody to hepatitis B core antigen; ALP, alkaline phosphatases; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma glutamyl transpeptidase; HCV, hepatitis C virus; HIV, human immunodeficiency virus; ULN, upper limit of normal.
Among the 40 HCV-treated patients, 31 (77.5%) were also on HAART, which was modified in nine cases because of the HCV therapy. At the beginning of HCV therapy, abacavir was part of the HAART regimen in six cases and zidovudine in four cases, whereas neither didanosine nor stavudine were given. The median delay between the diagnosis of acute hepatitis and HCV treatment was 5 ± 5 months. Combination therapy with pegylated interferon (PEG-IFN) and ribavirin was used in 38 patients, whereas monotherapy with PEG-IFN alfa-2a was given in two patients: PEG-IFN alfa-2a in 36 cases at a dose of 180μg/week (except for one patient at 135 μg/week and for another at 360 μg/week), PEG-IFN alfa-2b in two cases at a dose of 1.5 μg/kg/week, and ribavirin at a mean dose of 15.3 ± 2.3 mg/kg/day (range, 800-1,200 mg/day).
The mean effective duration of HCV therapy was 39 ± 17 weeks, with no difference between patients according to HCV genotype. Psychological or psychiatric support was provided in 16 patients (40%) when necessary, and antidepressive therapy was given to 22 patients (55%). Growth factors were used in 16 (40%) patients (epoietin in 11 patients and/or granulocyte stimulating factors in seven patients). Blood concentrations of ribavirin were assessed in five patients. Treatment doses were reduced in six (15%) patients (four PEG-IFN and two ribavirin), despite the use of supportive measures in four of them. HCV therapy had to be stopped because of poor tolerance in five (12.5%) patients (after a mean delay of 33 ± 13 weeks [range, 13-45]).
On treatment, 18/36 (50.0%; 95% CI 34.3-65.7) patients had undetectable HCV RNA at week 4 (rapid virological response [RVR]) and 32/37 (86.5%; 95% CI 75.7-97.2) had undetectable HCV RNA at week 12. Finally, 32/39 (82.1%; 95% CI 70.0-94.1) patients reached sustained virological response (SVR). The remaining patient (with undetectable HCV RNA at the last assay) has not yet reached the SVR assessment point (6 months after the cessation of anti-HCV therapy). Among the seven (18.4%) patients who did not achieve SVR, two were relapsers, whereas five never responded to HCV therapy. One of these patients was treated with PEG-IFN in monotherapy. Among the five patients who stopped their treatment prematurely, one did not reach SVR (after 13 weeks of therapy), whereas four achieved SVR (range of HCV therapy duration, 30-45 weeks).
Even though SVR was obtained in all of the patients infected with HCV genotype 3, there was no statistically significant difference between those infected with HCV genotype 3 and those without HCV genotype 3 (6/6 versus 24/31; P = 0.20). No significant association between other pretreatment parameters and SVR was observed (particularly regarding the HCV viral load or the delay between diagnosis and treatment).
By contrast, RVR on treatment tended to be significantly associated with SVR. Indeed, 17/29 (58.6%) patients with SVR had RVR versus 1/6 (16.7%) of those patients without SVR (P = 0.06). Complete suppression of HCV replication at week 12 was also significantly associated with SVR: 30/30 (100%) versus 1/6 (16.7%) of those without SVR (P < 0.0001). The positive predictive value of SVR associated with complete response at week 4 and week 12 was thus 94.4% and 96.8%, respectively. All but one (87.5%) of the eight patients with RVR achieved SVR following 24 ± 4 weeks of treatment, which contrasts with 2/6 (33.3%) of those who did not experience RVR (P = 0.09). The positive and negative predictive values of a complete response at week 4 and week 12 according to the duration of HCV therapy are shown in Table 2. Finally, the SVR rate was significantly lower in patients with HCV therapy shorter than 24 ± 4 weeks, compared with therapy longer than 28 weeks: 9/14 (64.3%) versus 23/25 (92.0%) (P = 0.04).
| SVR to a Short Treatment | SVR to a Long Treatment | |||||
|---|---|---|---|---|---|---|
| Treatment < 28 Weeks (Short Treatment) | Treatment >28 Weeks (Long Treatment) | Positive Predictive Value | Negative Predictive Value | Positive Predictive Value | Negative Predictive Value | |
| Duration of treatment in weeks, mean ± SD | 23.8 ± 4.2 | 47.3 ± 15.0 | — | — | — | — |
| Undetectable HCV RNA, n (%) | ||||||
| At week 4 | 8/14 (57.1) | 11/22 (50) | 7/8 (87.5) | 5/6 (83.3) | 11/11 (100) | 1/11 (9.1) |
| At week 12 | 9/12 (75) | 23/25 (92) | 8/9 (88.9) | 3/3 (100) | 23/23 (100) | 2/2 (100) |
| SVR 6 months after cessation of HCV therapy, n (%) | 9/14 (64.3) | 23/25 (92) | — | — | — | — |
- Data represent only the 39 patients who reached 6 months after the completion of HCV therapy.
- Abbreviations: HCV, hepatitis C virus; SVR, sustained virological response.
Discussion
In sharp contrast to the natural history of chronic hepatitis C in HIV-infected patients, which is likely to occur following acute infection in more than 80% of patients, the main result of the present study is that HCV clearance may be obtained in more than 80% of HIV-infected MSM, either spontaneously or following anti-HCV therapy. This result does not appear to be associated with any particular characteristics of our cohort of patients, because the definition, the circumstances of diagnosis and the characteristics of acute hepatitis C in our study were close to those generally used and reported. Indeed, the diagnosis of acute hepatitis C was also frequently associated with that of other sexually transmitted diseases.6 Such a high rate of concomitant infections highlights the very high-risk sexual behaviour of these patients, underlining the need for reinforced education. Most of the patients were on HAART with controlled HIV replication at the time of acute hepatitis C, and nearly half had a CD4 count above 500/mm3. Nearly one-third of patients presented clinical symptoms, as previously reported (32%-48%),7, 8 as well as the mean maximal ALT elevation (from 261 to 937 IU/L).7, 8 HCV genotype 4, which is the most prevalent genotype in France and has been also been frequently reported in the Netherlands, is nevertheless outweighed by genotype 1 in other Western countries.9 A specific cluster effect, therefore, cannot be excluded.
The spontaneous clearance rate of HCV we observed following the diagnosis of acute hepatitis C was only 11% 3 months after diagnosis (i.e., lower than that reported in HIV-negative patients) but was within the rather wide range (4%-40%) reported in HIV-positive patients.2, 10-15 A higher baseline median CD4+ lymphocyte count (particularly at 500 cells/mm3),16 a lower baseline median HCV viral load,16 and a rapid decline of HCV RNA levels within 4 weeks following diagnosis14 were previously found to be associated with spontaneous clearance. We failed to observe such an association, perhaps because of a lack of power linked to this low rate of spontaneous HCV clearance. It is indeed possible that this rate could be higher than the 11% we observed, particularly because 21 (51%) patients were treated during the first 3 months following the diagnosis of infection. These patients could have spontaneously cleared their infection if HCV therapy had been deferred. Some authors have proposed waiting 12 weeks, not from the diagnosis but from the estimated date of exposure, before beginning HCV therapy.5 Deferring HCV therapy a few months from the date of exposure may be confusing, because the date of exposure may be uncertain, and because the time between exposure and diagnosis often exceeds several months. In the same way, deferring HCV therapy a few months from the date of diagnosis may be misguided, considering the low rate of spontaneous clearance we observed 3 months later in our 21 patients who were uncensored at this time. Because it is likely that each month spent with uncontrolled HCV replication and the evolution toward chronic hepatitis C would contribute to a reduction in the response rate to further anti-HCV therapy, as shown in HIV-negative patients,17 it is likely that there is no real benefit to postponing HCV therapy more than 3 months after the diagnosis of acute hepatitis C. In addition, it has been reported that the spontaneous disappearance of HCV RNA could be temporary, but nevertheless could lead to chronic hepatitis C,13 even though this was not observed in our study.
This finding could swing the pendulum toward immediate or at least earlier treatment of acute hepatitis C, because the overall SVR following HCV therapy in our homogeneous cohort of HIV-infected MSM was 81.6% (and was as high as 83.3% when considering only the 39 patients treated with PEG-IFN and ribavirin). This rate is higher than that initially reported in HIV-infected patients (50%-71%)10, 13, 16, 18, 19 but is very close to that reported in two recent studies (78%-80%).8, 20 Several factors could explain this high rate, such as the use of combination therapy, satisfactory safety, and/or the frequent use of psychiatric or hematological supportive measures as recommended for HCV therapy in chronic hepatitis, and/or the duration of treatment longer than 24 weeks in half of the cases (and even longer than 52 weeks for 20% of them). It should also be noted that no significant association between pretreatment parameters (including HCV genotype) and SVR was observed. However, it has to be acknowledged that the impact of other factors, in particular IL28B polymorphism, which has been shown to have a strong impact on chronic hepatitis C treatment outcomes in HIV-infected patients, was not studied in the present study.21
In HCV monoinfected patients, a few trials have shown that PEG-IFN monotherapy could be associated with high response rates (72%-94%).22-25 In the same way, the study of Vogel et al.13 in 36 HIV-infected patients showed a nonsignificant trend toward a better virological response in patients on PEG-IFN monotherapy compared with those with added ribavirin. The different studies performed in HIV-infected patients were unable to show whether or not adding ribavirin increased the SVR rate. It has been advocated that monotherapy with PEG-IFN would result in fewer side effects, less interaction with antiretroviral agents, and lower pill burden, possibly leading to better compliance and higher chances of completing therapy.26 It has also been suggested that retreatment in case of failure may be easier if the patient is still naïve to ribavirin. However, it has been shown that more aggressive treatment of chronic hepatitis C is needed in HIV-infected patients, and it may be speculated that retreatment in case of previous failure is expected to have lower chances of response considering the time elapsed from HCV contamination. Early results with monotherapy using standard or PEG-IFN therapy were clearly disappointing.11 Thus, most recommendations state that combination therapy associating PEG-IFN and ribavirin has to be used in these patients.5 The interest of combination therapy could not be assessed directly in our study either, because only two patients were on PEG-IFN monotherapy. Nevertheless, it must be noted that the three recent studies (including ours) reaching a 10% higher rate of SVR (close to 80%) compared with previous ones concerned patients on HCV therapy that included ribavirin.8, 20 As in our study, in which many supportive measures were used, better knowledge of the prevention and management of the side effects of HCV therapy probably played a role in these results, because it allowed most patients to receive at least 80% of the initially scheduled dose of PEG-IFN and ribavirin.8 The rate of premature discontinuation of treatment was thus quite low (12%) and often occurred late (after 33 weeks of treatment) in virologically controlled patients.
This finding raises the question of the optimal duration of HCV therapy. The usually recommended duration of HCV therapy in acute hepatitis C in HIV-infected patients is 24 weeks.5 It must be noted that the best 80% SVR rate was reached with 24 weeks of HCV therapy,8, 20 even though 25%-33% of the patients in these studies harbored HCV genotype 3. Only one study in HIV-infected patients showed that a 48-week treatment resulted in a greater likelihood of SVR than did a 24-week treatment (89% versus 52%; P = 0.04), but the number of patients (n = 9 for the 48-week group) was too small to draw any definite conclusions.13 In our study, a significantly higher rate of SVR was also observed in patients treated for more than 28 weeks compared with those treated for a shorter duration (92.0% versus 64.3%; P = 0.03). As previously suggested,8 it is likely that RVR would be of help in determining the optimal duration of treatment for acute hepatitis C in HIV-infected patients. Indeed, the rate of SVR following 24 weeks of HCV therapy was quite high in patients with RVR (87.5%), albeit lower than the 100% observed in the Australian Trial8 and the 93% observed in a multicenter European cohort study.15 These high positive predictive values of RVR on SVR suggest that a 24-week course is likely to be a relevant option in cases of RVR. By contrast, the significantly lower rate of SVR following 24 weeks of HCV therapy in patients without RVR (25.0%), even lower than the 43% of the European cohort study,15 should lead physicians to offer a 48-week course of HCV therapy, because with this duration the rate of SVR did not significantly differ whether RVR was obtained or not.
In conclusion, our study suggests that the probability of HCV clearance at the acute phase of infection in HIV-infected patients is approximately 15% at 6 months. This low rate and the high SVR rate (82.1%) associated with HCV therapy strongly argue for immediate/early treatment following diagnosis. PEG-IFN combined with ribavirin at weight-based doses seems to be the best option, considering that the best results were obtained on such a combination therapy. Safety data are encouraging, even though supportive measures have to be frequently used as for the treatment of chronic hepatitis C. The duration of treatment should be modulated according to RVR, with a 24-week course for patients presenting RVR and a 48-week course for those who do not, irrespectively of the HCV genotype. The lack of complete response at week 12 should lead physicians to consider treatment discontinuation.
Acknowledgements
We thank all the patients who agreed to participate, Sandrine Treuvelot and Corinne Pioche for their contribution in the management of this study, and Philip Bastable for his help in reviewing the manuscript. We are also indebted to the physicians who participated to the present study, particularly H. Aumaitre, C. Chaumie, L. Cuzin, Y. Debab, S. Faouzi, C. Fontaine, C. Gaud, J. M. Jacquet, H. Melliez, P. Miailhes, D. Parlier, F. Raffi, J. M. Ragnaud, D. Rey, R. Verdon, P. Yeni, D. Zucman, and O. Zineb.
