HCV treatment rates reported by providers at the three participating sites ranged from 10%, which is similar to those found in the literature,6–12
to as high as 38%. With providers being the primary gatekeepers of treatment access, we sought to examine how the decision making process differs across the primary care providers at these three sites.
Stable HIV disease is clearly a basic tenet to HCV treatment being considered. Providers at each of the three sites preferred CD4 counts to be in the 300s and certainly greater than 200 before treatment could be considered. This is consistent with published HCV treatment guidelines for HIV patients,21
and evidence that HCV treatment is more successful with higher CD4 counts,25
and that HCV treatment depletes CD4 cells during the course of treatment, rendering patients vulnerable to opportunistic infections.37
With a stable HIV disease, providers then shift their focus to the patient's HCV and stage of liver disease. All providers agreed that late stage, decompensated liver disease was a treatment contraindication due to the risk of serious side effects, and that the few patients with genotype 2 or 3 should be treated when at all possible given the high treatment response rates in these patients. Furthermore, there was general consensus that genotype 1 and 4 patients with significant signs of disease, fribrosis and liver inflammation should be treated.
Where these clinics and providers differed was in the treatment of genotype 1 and 4 patients who have no or minimal signs of liver disease. At sites with lower treatment rates, providers preferred to delay treatment for these patients, citing low treatment response rates, high toxicity burden, and better treatment options on the horizon, thus weighing the costs of treatment to be greater than the likely benefits. Providers at Site C (and some at Site B), who reported higher treatment rates, viewed all patients as needing treatment as soon as possible regardless of whether or not there were signs of disease; these providers cited the added risk for rapid disease progression associated with HIV,38
the greater likelihood of treatment success with milder disease,39
the chance of a cure, and the confidence to help patients successfully manage side effects. Provider attitudes toward liver biopsies were influenced by this decision process as providers who preferred to treat these patients saw little or no value in having a biopsy done, whereas providers who would rather defer treatment viewed biopsies as being able to confirm the stage of liver disease and treatment decision. Yet regardless of these attitudes, biopsies are not needed to provide treatment at these sites and each site reported that very few biopsies had been performed on their patients.
Given the low uptake of treatment reported in the literature,6–12
and studies that report mild liver disease to be a common reason for treatment ineligibility,28,40
it appears that most providers in the field side with those who favor the “wait and monitor” approach for genotype 1 and 4 patients with mild disease. This approach aims to spare the patient from having to endure a toxic treatment that for most will provide no virologic benefit, so long as the patient's liver disease does not progress significantly. Providers must balance waiting for indicators of significant liver disease progression with the risk of waiting too long such that treatment is likely to be less successful or even contraindicated because the liver disease is too advanced or because CD4 count drops too low, both of which are common reasons for coinfected patients being excluded from HCV treatment.7
Whether a patient is treated early in the disease stage, or not until there are at least moderate signs of disease progression, would not have significant policy implications if treatment was in fact eventually started. But the low treatment rates reported in the literature, and data showing that most coinfected patients have at least moderate signs of fibrosis,4,5
highlight the role that nondisease factors play in treatment decision making.
Regardless of whether providers prefer to treat early or delay treatment depending on disease stage, they must still assess the patient's psychosocial readiness for treatment. All providers agreed on the key components of readiness, those being patient motivation and interest in treatment, demonstration of ability to adhere to treatment and clinic appointments, and a mental health status that will not impede ability to adhere and tolerate treatment. These readiness components account for a large proportion of the patients not being treated.6–12
However, while there was general agreement on the components of readiness, there was considerable variation in how providers viewed the influence of depression and substance use in determining a patient's readiness for treatment.
Mental illness and substance use are leading causes for treatment deferment,6–8,27,28
and thus are prime reasons why many patients with significant liver disease continue to be untreated. Yet the empirical evidence is mixed with regard to the effects of these conditions. A number of studies have found that HCV treatment response and completion rates do not differ between patients with or without histories of psychiatric illness or substance abuse, nor between active drug users and nonusers.29–31,41,42
However, other studies have found that patients with past psychiatric problems are more likely to need psychiatric care during HCV treatment43
and that patients who are depressed at treatment baseline are less likely to respond to treatment.44
While all providers in the study called on mental health screens and clearance for some patients, and required that serious mental illness be stabilized by psychiatric treatment prior to initiating HCV treatment, the views on depression varied. Most providers spoke of the need to use antidepressants to stabilize current depression before starting HCV treatment, and some used antidepressants as a prophylactic for patients with past depression. However, the provider who reported the highest treatment uptake had the most lenient approach, indicating that untreated moderate depression would not prevent prescription of HCV treatment, and that it was up to the patient to decide whether or not they wanted depression treatment prior to starting HCV therapy once they were informed of the possible options and risks of not treating the depression.
There was even more variation in how the providers viewed current use of alcohol and illicit drugs. A few providers spoke of no tolerance for any alcohol and drug use for 6 months prior to the patient being considered ready for treatment, which is a common standard in the field.45
But several experts and patient advocates have called for a more flexible approach—one that looks at the individual circumstances for each patient.29,46
All providers in the study spoke of strongly encouraging their patients to abstain from use of alcohol and drugs, but several conceded that there was a “gray zone” in judging this criteria and that they would allow an occasional drink or use of marijuana, but not harder drugs. Similar to evaluations of mental health, the providers at the site with the highest treatment rate were most willing to offer treatment to patients who were actively using drugs such as crystal methamphetamine, so long as the patient convinced them that they could still adhere to treatment.
In conclusion, findings from this study highlight two approaches to managing HCV treatment decisions. One views treatment initiation as more urgent and is willing to accept the risk of a more lenient definition of patient readiness for treatment. The other takes a more cautious approach with a preference for holding off treatment until it is clear that a patient's liver disease is in need of treatment and the patient has all the signs of being ready to adhere well. There is no clear evidence indicating whether one approach is more appropriate than the other. An urgent approach to treatment results in more patients being treated and thus more patients being “cured,” but also more patients who endure significant side effects that compromise mental health and quality of life without virologic benefit.
Conversely, delaying treatment can reduce unnecessary burden on a patient's quality of life, and better, less toxic treatment may become available before the patient's disease progresses to the point of definitively needing treatment; however, ultimately treatment is needed to avoid liver failure and the longer a patient waits, the lower the odds of treatment being successful with the currently available treatment. Regardless of which approach may be more appropriate, development of effective programs for promoting patient readiness for treatment are critical to ensuring that more patients receive treatment, either earlier in the disease or later, given the high mortality associated with liver disease among HIV/HCV coinfected patients.
Finally, the examination of treatment uptake rates and the treatment decision making process cannot be fully understood without accounting for the role of the patient and their decision process for requesting, accepting or refusing treatment. Provider decisions to recommend or offer treatment is critical to providing treatment access, but whether or not a patient starts treatment is ultimately in the hands of the patient. Studies show that 10%–20% of HIV coinfected patients choose to refuse HCV treatment.47
In addition to analyzing the qualitative interviews of coinfected patients who participated in this study, we will soon conduct a quantitative survey of HCV providers and their HIV coinfected patients. The goal of these assessments is to better understand the multilevel factors that contribute to the treatment decision making of both providers and patients, and to inform the development of intervention strategies for improving HCV treatment uptake and outcomes for HIV coinfected patients.