A study from the US 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 people with HIV/HCV co-infection were less likely to be cured. These conflicting findings, presented at the recent International Liver Congress in Barcelona, indicate that the interactions between HIV and hepatitis C are still not fully understood.
Approximately one-third of people with HIV are co-infected with hepatitis C virus (HCV). Individuals with co-infection 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 of the University of Southern California and colleagues performed an analysis of the impact of HIV co-infection 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%) had HIV/HCV co-infection. 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 (Incivo or 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 (Viekirax/Exviera). Demographic characteristics were similar across treatment groups; however, a greater proportion of patients who received sofosbuvir plus simeprevir had cirrhosis and were 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 patients with HIV/HCV co-infection 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 co-infection on treatment effectiveness (odds ratio 1.07).
"The overall rates of SVR12 exceed 88% across all 3 treatments analysed, regardless of HIV co-infection status," the researchers concluded. "The results from logistic regression analysis indicate that HIV co-infection does not significantly impact the likelihood of achieving a sustained virologic response for patients using the treatments studied."
GEHEP-MONO and HEPAVIR-DAA cohorts
Another analysis, however, reached a different conclusion.
Karin Neukam of Hospital Universitario de Valme in Seville and colleagues evaluated the impact of HIV co-infection 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 mono-infected participants in the GEHEP-MONO cohort and 596 patients with HIV/HCV co-infection 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 three-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 mono-infected patients, falling to 55% for HIV/HCV co-infected patients, a significant difference (p = 0.019). Cure rates using interferon-free DAA regimens were 95% and 89%, respectively, also significantly different (p = 0.002).
In a multivariate analysis adjusted for age, sex, HCV genotype and baseline HCV viral load, HIV/HCV co-infection 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 co-infected patients seem to respond worse to DAA-based therapy than HCV mono-infected 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 play a role."
"These differing data confirm that the study of HCV treatment in HIV co-infected 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 co-infected patients."
McGinnis J et al. Analysis of the impact of HIV co-infection on hepatitis C treatment effectiveness for patients using new direct-acting antivirals. International Liver Congress, Barcelona, abstract LBP514, 2016.
K Neukam, M Suárez-Santamaría, A Rivero-Juárez, et al. HIV coinfection impairs response to DAA-based HCV therapy. International Liver Congress, Barcelona, abstract LBP513, 2016.