Hepatitis C treatment as prevention among HIV‐infected men who have sex with men: Feasible?
Authors: Gregory J. Dore
Journal: Hepatology (2016)

Potential conflict of interest: Gregory J. Dore is a consultant/advisor and has received research grants from Abbvie, Bristol Myers Squibb, Gilead, Merck, and Janssen. The Kirby Institute is funded by the Australian Government Department of Health and is affiliated with the Faculty of Medicine, UNSW Australia. The views expressed in this publication do not necessarily represent the position of the Australian Government. G.J.D. is a recipient of the National Health and medical Research Council Practitioner Fellowship. See Article on Page 1856 An estimated 64‐103 million people are living with chronic hepatitis C virus (HCV) infection globally.1 The World Health Organization recently released a series of goals toward the elimination of viral hepatitis, including chronic HCV targets of 90% diagnosed, 80% treated, and 65% reduction of mortality by 2030. These ambitious goals follow a major transformation in HCV treatment in which direct‐acting antiviral (DAA) regimens have led to marked increases in therapy uptake in many countries. Advances in HCV therapy have also led to discussion of the potential for HCV treatment as prevention. Treatment as prevention (TasP), which was used initially within the context of human immunodeficiency virus (HIV) therapy, incorporates treatment as a tool for limiting the spread of infection in generalized epidemics in a particular setting. Key at‐risk populations for HCV infection include people who inject drugs (PWID) and HIV‐infected men who have sex with men (MSM). Although empirical clinical studies to evaluate HCV TasP are clearly required, mathematical modeling can provide valuable insight into the potential of therapeutic intervention to provide population‐level transmission impact. Several modeling studies have explored the potential of HCV TasP among PWID and HIV‐infected MSM. One study evaluated DAA therapy scale‐up in three settings with different chronic HCV prevalence among PWID: Edinburgh, Scotland (25%), Melbourne, Australia (50%), and Vancouver, Canada (65%).2 Employing DAA therapy with 90% cure and 8% annual treatment uptake among current PWID could achieve near elimination of HCV (<5% prevalence) by 2022 in Edinburgh, and 2027 in Melbourne, but not in Vancouver by 2027 (30% prevalence).2 This study highlights the opportunity for HCV TasP but also reveals the challenges associated with settings of very high population prevalence. Among HIV‐infected MSM in the United Kingdom, modeling has indicated that an increasing HCV prevalence would be expected in an interferon‐containing therapeutic setting. However, using interferon‐free DAA therapy with a treatment uptake of 80% among recent HCV diagnoses and 20% per annum among nonrecent diagnoses would reduce chronic HCV prevalence from approximately 9% to 3% within 10 years.3 Of note, these HCV treatment scenarios were established in models that assumed stable HCV incidence. In this issue of Hepatology, Salazar‐Vizcaya et al.4 present further mathematical modeling evaluation of HCV TasP among HIV‐infected MSM in Switzerland. There are key strengths to this study, particularly in light of the marked increase in high‐risk sexual behavior and HCV incidence among HIV‐infected MSM in the past decade. First, using detailed patient demographic, clinical, and behavioral data derived from the Swiss HIV Cohort Study (which included 73% of diagnosed HIV patients in Switzerland) provides internal consistency. Second, the evaluation of DAA therapy scale‐up rate scenarios together with high‐risk sexual behaviour change scenarios provides both sophistication and public health relevance. The most striking finding is the impact of high‐risk sexual behavior on DAA TasP. In the "pessimistic scenario," wherein the proportion of HIV‐infected MSM engaging in high‐risk sexual behaviors (e.g., condomless anal intercourse, group sex, and fisting) increases to above 20% (after increasing from 5% in 2000 to 13% in 2013), even treating 100% of new HCV infections per annum with DAA therapy would not prevent further increases in HCV incidence and prevalence. In the more likely "intermediate scenario," which represents a small increase in high‐risk sexual behaviors with "saturation" at a proportion of approximately 15%, even treating 22% of new HCV infections per annum with DAA therapy (similar to the treatment rate in the latter interferon‐containing period within the Swiss HIV Cohort Study) would prevent a further increase in HCV incidence. In this scenario, treating 100% of new HCV infections per annum with DAA therapy would markedly reduce HCV incidence and lead to effective elimination of HCV (prevalence <1.0%) by 2030. Similar effects on HCV incidence and prevalence toward elimination can be achieved under the "optimistic scenario" through a reduction of high‐risk sexual behavior and a DAA therapy uptake of only 22% per annum. This study clearly demonstrates the link between the ongoing level of HCV risk behavior and the potential impact of HCV TasP strategies. There are several questions to be addressed in relation to potential population‐level impacts of HCV treatment on transmission. Extremely high clinical trial DAA efficacy does appear to be translating into similar "real world" outcomes among generally nonmarginalized patient populations.5 However, will these favorable outcomes be sustained? Furthermore, what outcomes will be achieved among key TasP populations, such as highly marginalized PWID? Access to DAA therapy is highly variable, with liver disease stage and drug and alcohol restrictions in many settings. Thus, will both access and demand for DAA therapy among key populations produce treatment uptake sufficient to achieve population‐level TasP outcomes? Finally, could HCV therapeutic optimism produce increased risk behavior among PWID and HIV‐infected MSM, and therefore limit TasP impact as demonstrated in the Swiss modeling study? Ongoing high‐risk behavior—including unsafe injections among PWID and unsafe sex among HIV‐infected MSM—has the potential to produce high rates of both initial HCV infection and HCV reinfection following successful HCV treatment. A recent meta‐analysis demonstrated post‐sustained virologic response reinfection rates of 0.2% per annum for individuals without reported risk behavior, 2.2% per annum among high‐risk PWID and prisoner populations, and 3.2% per annum among individuals with HIV coinfection.6 Particularly high HCV reinfection rates of 8% and 15% per annum were demonstrated in two studies of HIV‐infected MSM.6 Another modeling study revealed that even with stable rates of ongoing HCV risk behavior, increasing numbers of HCV reinfections will be seen with higher treatment levels, particularly in the initial years of DAA therapy scale‐up.7 However, sustained HCV treatment scale‐up—including access to retreatment for reinfection—will reduce the HCV viremic pool among high‐risk populations, which will in turn lead to an eventual reduction in reinfections. Although the Swiss HIV Cohort Study provides a reality check with regard to the potential for TasP, there are several reasons why HCV elimination may be feasible in specific population groups in particular settings. For example, HCV elimination among people with HIV in Australia should be feasible, given the relatively small population of HIV/HCV‐coinfected individuals (an estimated 2700), a predominantly nonmarginalized population of MSM, and the involvement of primary care‐based HIV prescribers.8 The CEASE study in Australia is a 5‐year project that is evaluating the scale‐up of DAA therapy and population‐level HCV transmission impact within HIV/HCV‐coinfected individuals. The recent Australian government subsidization of DAA therapy for all adults with chronic HCV—with no liver disease or drug and alcohol use restrictions and prescription by general practitioners—provides the foundation for HCV TasP implementation. HCV treatment education for general and other practitioners involved in HIV treatment has been undertaken to encourage an uptake in HCV prescriptions. In the first 4 months (March‐June 2016) of DAA therapy access, an estimated 10% of individuals with chronic HCV in Australia have commenced therapy, with a likely much higher proportion among the HIV/HCV‐coinfected population. The broad goal of the CEASE study is to eliminate HCV as a significant public health issue for people with HIV in Australia by 2020. The Australian situation provides an example of an ideal setting for TasP evaluation, given the broad access and encouraging initial uptake of HCV treatment. Similar DAA therapy programs, including access to treatment of reinfection, will be required in other settings to move toward global targets for the elimination of HCV. Clearly, other components will be pivotal, including massively enhanced HCV screening programs in most countries and effective linkage to care. However, the unique times in which we live provide an opportunity to meet these ambitious targets.