We read with interest the report by Feuerstadt et al.1 demonstrating the limited effectiveness of hepatitis C virus (HCV) therapy in an urban minority population. We evaluated 432 similar HCV-monoinfected patients and 392 human immunodeficiency virus (HIV)/HCV-coinfected patients and treated 45% and 21%, respectively. The baseline characteristics of our patients and theirs were similar, although more coinfected patients had advanced fibrosis (Table 1). Sustained virological response (SVR) was achieved in 21% of their subjects, 35% of our monoinfected patients, and 22% of our coinfected patients. In addition to the reported negative predictors of SVR, our coinfected patients had high mean HCV viral loads and a 14% prevalence of diabetes. A previous study of coinfection from our institution found a 76% prevalence of a homeostasis model assessment of insulin resistance score >3.2 Nasta et al.3 reported an 8% rapid virological response rate in coinfected patients with a high viral load and a homeostasis model assessment score >3.
|HCV Monoinfection||HIV/HCV Coinfection: SLRHC|
|Feuerstadt et al.1||SLRHC|
|Age, years||50.0 ± 8.6||54.4 ± 8.3||51.0 ± 8.0|
|Weight, kg||84.4 ± 18.9||80.1 ± 16.4||79.4 ± 15.0|
|HCV RNA level, IU (×106)||Unknown*||1.2 ± 2.1||2.2 ± 2.9|
|HCV RNA level >400,000 IU, %||50||47|
|Genotype 1, %||68||72||78|
|Bridging fibrosis or cirrhosis, %||29†||21 (F3-F4)||59 (F3-F4)|
|Baseline ALT, IU/L||98 ± 97.0||67 ± 63||78 ± 59|
|SVR, % of total treated||21||35||22|
|Genotypes 1 and 4||14||25||22|
|Genotypes 2 and 3||37||59||53|
Feuerstadt et al.'s study1 did not concentrate on race or gender effects on SVR. In our cohort, the SVR rate in genotype 1–coinfected non-Caucasian men was strikingly low at 7.3% (3 of 41) versus 27.3% in genotype 1–infected Caucasian men and 36% in genotype 1–infected non-Caucasian women. It is unlikely that the results were due to poor adherence because the HIV control was well maintained in this subgroup with a mean CD4 level of 556 cells/mm3, undetectable HIV RNA in 67%, and a similar dropout rate (24%) in comparison with other subgroups (25%).
A polymorphism near the interleukin-28B (IL-28B) gene encoding interferon lambda 3 is the strongest predictor of SVR in genotype 1 patients and doubles the SVR, rapid virological response, and early viral response rates in patients of all ancestries.4, 5 The CC genotype is more prevalent in Caucasians than in African Americans or Latinos in the Western Hemisphere, and this helps to explain ethnic disparities in treatment response. Rallón et al.6 confirmed the association of the CC genotype with treatment response in HIV/HCV-coinfected Caucasian patients.6 Although IL-28B polymorphisms have important implications for immunomodulating therapies, they also may modify the effectiveness of antiviral therapy. IL-28B polymorphisms and amino acid substitution in the HCV core region predicted SVR to telaprevir, pegylated interferon, and ribavirin.7
Mehta et al.8 reported an SVR rate of 21% in treated patients in an urban HIV clinic but only 0.7% in the full cohort; the latter was due to a low referral rate. New treatment strategies are needed for HCV-infected and HIV/HCV-coinfected patients in urban settings because of the low rates of SVR, particularly in genotype 1 HIV–infected non-Caucasian men. If a larger series corroborates these results, maintaining the current standard of care in this subpopulation of HCV-infected individuals should be questioned. Using IL-28B genotyping to assist with treatment decisions and deferring therapy until new targeted therapies are available should be considered. Clinicians are faced with the dilemma of recommending immediate treatment or warehousing patients (i.e., foregoing standard-of-care treatment) in anticipation of novel therapies. Finally, when clinicians discuss the possible benefits and risks of hepatitis C therapy, the sobering, real-world treatment results should be made available to their patients.