EASL 2016: Does Having HIV Affect Response to Hepatitis C Treatment?


A study from the U.S. Veterans Health Administration found that HIV-positive people responded as well as those without HIV to direct-acting antiviral (DAA) therapy for hepatitis C, while a Spanish study showed that HIV/HCV coinfected people were less likely to be cured. These conflicting findings, presented at the European Association for the Study of the Liver's International Liver Congress (EASL 2016) last month in Barcelona, indicate that the interactions between HIV and hepatitis C are still not fully understood.

Approximately one-third of people with HIV are coinfected with hepatitis C virus (HCV). Coinfected individuals experience more rapid liver disease progression, on average, and in the era of interferon-based therapy they did not respond as well to treatment. But some recent studies have suggested that this disparity in treatment response does not apply to interferon-free DAA regimens.

Veterans Health Administration Study

Justin McGinnis from the University of Southern Californiaand colleagues performed an analysis of the impact of HIV coinfection on the real-world effectiveness of hepatitis
C treatment using DAA regimens.

The study included 9604 hepatitis C patients -- almost all men -- treated within the Veterans Health Administration prior to September 2015. Of these, 408 (4.3%) were HIV/HCV coinfected. A majority (75%) had HCV genotype 1, 48% had liver cirrhosis, and 8% had received prior treatment using the first-generation DAAs boceprevir (Victrelis) or telaprevir (Incivek).

About a third were treated with sofosbuvir (Sovaldi) plus simeprevir (Olysio), 58% received sofosbuvir/ledipasvir (Harvoni), and 11% received the ombitasvir/paritaprevir/ritonavir/dasabuvir 3D regimen (Viekira Pak). Demographic characteristics were similar across treatment groups; however, a greater proportion of patients who received sofosbuvir plus simeprevir were cirrhotic and in more urgent need of treatment.

Participants had at least 12 weeks of post-treatment follow-up data available. Effectiveness was defined as achieving sustained virological response (SVR), or continued undetectable HCV viral load at least 12 weeks after completing treatment.

The overall SVR rates were 87% with sofosbuvir plus simeprevir, 93% with sofosbuvir/ledipasvir, and 93% with the 3D regimen. The corresponding cure rates for HIV/HCV coinfected patients were 88%, 93%, and 89%, respectively -- none of which were significant differences.

Across study treatments, a multivariate analysis controlling for patient demographics, disease severity, and co-morbidities did not find a statistically significant impact of HIV coinfection on treatment effectiveness (odds ratio 1.07).

"The overall rates of SVR12 exceed 88% across all 3 treatments analyzed, regardless of HIV coinfection status," the researchers concluded. "The results from logistic regression analysis indicate that HIV coinfection does not significantly impact the likelihood of achieving a sustained virologic response for patients using the treatments studied."


Another analysis, however, came to a different conclusion.

Karin Neukam from Hospital Universitario de Valme in Seville and colleagues evaluated the impact of HIV coinfection on the efficacy and safety of DAA treatment, with or without interferon, among patients in a real-world clinical setting.

This prospective analysis included 680 hepatitis C monoinfected participants in the GEHEP-MONO cohort and 596 HIV/HCV coinfected patients in the HEPAVIR-DAA cohort who received DAA treatment in outpatient clinics at 33 hospitals throughout Spain since October 2011. About three-quarters were men and the median age was approximately 52 years. The most common HCV genotypes were 1a and 1b. About 60% had received previous hepatitis C treatment and a similar proportion had cirrhosis.

Just over 40% received 3-drug combinations of pegylated interferon and weight-based ribavirin along with sofosbuvir, simeprevir, boceprevir, or telaprevir. The rest (57%) received interferon-free regimens including sofosbuvir with either simeprevir, ledipasvir, or daclatasvir (Daklinza), or the 3D regimen or a similar combination without dasabuvir (known as 2D), all with or without ribavirin.

SVR12 rates using interferon-containing therapy were 66% for HCV monoinfected patients, falling to 55% for HIV/HCV coinfected patients, a significant difference (p=0.019). Cure rates using interferon-free DAA regimens were 95% and 89%, respectively, also significant (p=0.002).

In a multivariate analysis adjusted for age, sex, HCV genotype, and baseline HCV viral load, HIV/HCV coinfection was independently associated with a lower likelihood of sustained response (adjusted odds ratio [aOR] 0.59), as was liver cirrhosis (aOR 0.60), while use of interferon-free therapy increased the likelihood of a cure (aOR 7.93). Specific DAA regimen, treatment duration, use of ribavirin, prior treatment experience, and baseline HCV viral load were not significant predictors of response.

"HIV/HCV coinfected patients seem to respond worse to DAA-based therapy than HCV monoinfected subjects," the investigators concluded.

"The underlying reason for this finding is unclear," they added. "The poorer immune response against HCV, adherence issues, or severity of liver damage could theoretically pay a role."

"These differing data confirm that the study of HCV treatment in HIV coinfected patients remains an interesting and valuable subject for study," commented EASL secretary general Laurent Castera. "More research is needed to come to a viable resolution so we can provide the best care for these coinfected patients."



J McGinnis, J McCombs, D Mehta, et al. Analysis of the impact of HIV co-infection on hepatitis
C treatment effectiveness for patients using new direct-acting antivirals. EASL International Liver Congress 2016. Barcelona, April 13-17, 2016. Abstract LBP514.

K Neukam, M Suárez-Santamaría, A Rivero-Juárez, et al. HIV coinfection impairs response to DAA-based HCV therapy. EASL International Liver Congress 2016. Barcelona, April 13-17, 2016. Abstract LBP513.

Other Source

EASL. Differing perspectives on antiviral treatment efficacy in patients co-infected with HIV and HCV. Press release. April 13, 2016.