HCV-infected persons are frequently not prescribed treatment.4–6
Various studies have reported factors associated with nonprescription of treatment, but the proportion of HCV-infected persons actually eligible for treatment per the current guidelines is not well known. We studied a large national sample of HCV-infected persons to determine treatment eligibility in HCV- and HCV-HIV-coinfected persons.
Even when indications for pharmacotherapy were present, a majority of subjects in both HCV-monoinfected and HCV-HIV-coinfected groups were ineligible for treatment due to the presence of at least one contraindication. HCV-HIV-coinfected persons were less likely to be eligible for treatment compared with the HCV-monoinfected subjects. Our finding that only ~44% of the HCV-monoinfected and ~28% of the HCV-HIV-coinfected persons were eligible for treatment should prompt healthcare providers and policy makers to address the modifiable contraindications to optimize care of this population.
The pattern of conditions that led to ineligibility for HCV treatment was somewhat different in the HCV-monoinfected and HCV-HIV-coinfected group. It has previously been demonstrated that HCV-HIV-coinfected persons have a higher prevalence of medical, psychiatric, and substance abuse comorbidities. We found that anemia, decompensated liver disease, renal failure, active psychiatric disease, and recent drug abuse or dependence were 1.5 to 2 times more prevalent in the HCV-HIV-coinfected persons, while coronary artery disease and alcohol use were less prevalent in the coinfected group. This is consistent with previous data comparing overall prevalence of comorbidities in these groups.4
These findings will help determine priorities for targeted intervention in both groups to improve treatment eligibility, and eventually treatment prescription. Conditions such as anemia, psychiatric disease, and substance abuse are potentially modifiable factors.
We found that HCV-HIV-coinfected subjects were less likely to be seen by a gastroenterologist/hepatologist compared with HCV-monoinfected persons. The reason for this is unclear, but possibilities include provider perception that they may be poor candidates for treatment, advanced HIV disease, and fear of drug toxicities or drug interactions. A higher prevalence of contraindications to treatment lends credence to the first possibility. CD4+ lymphocyte counts were available for 714 of the 1036 subjects who had indications for treatment; of those, 39.6% had at least one value less than 100 cells/mm3. We did not study the number of subjects on combination antiretroviral therapy, or whether such therapy led to any improvement in the CD4+ lymphocyte counts. The proportion of subjects that underwent a liver biopsy was less than 2% in each group. This is a strikingly low number, but should be interpreted with some caution, since we did not capture any biopsies that may have been performed outside the VA on a fee-for-service basis.
Even when subjects had indications for treatment and no contraindications, only a small number was prescribed treatment in either group. Treatment prescription rates were lower in the HCV-HIV-coinfected group (15%) compared with the HCV-monoinfected group (23%). The reasons for nontreatment when there are no contraindications to treatment are unclear, and need further study. It is possible that patient-, provider-, and healthcare system-level factors each plays some part in such a low level of treatment prescription for a disease that has been declared a priority in the veterans.
There are many strengths to this study. To our knowledge, this is the first national study of treatment eligibility, and directly compares HCV-monoinfected with HCV-HIV-coinfected persons. The study was conducted in veterans who received care at any of the VA medical facilities. The VA is the largest integrated healthcare system in the United States, and because of the computerized integration of records, and national coverage of eligible veterans, this system is able to track, follow, and treat patients even when they move from one geographic area to another. The number of subjects suggests that the VA healthcare system is one of the largest providers of healthcare to persons infected with HCV. It has been argued that the veterans in care are a nonrepresentative sample for the U.S. population in general. Veterans are predominantly men, and have a higher prevalence of several comorbidities compared with the general population. However, most HCV-infected persons in the United States are between 30 and 49 years old, are more likely to be black, and are more likely to have a higher rate of drug use. Furthermore, the prevalence of HCV is about twice as high in men as women,30
factors similarly seem among HCV-infected veterans in care.
Despite the strengths of our analyses, limitations of the VA data and large database analyses need to be understood. We may not have captured laboratory data on many subjects.29
The diagnosis of certain comorbidities was made on the basis of ICD-9 codes. Although we took care to use a narrow time window in an attempt to include only current or active diagnoses, some conditions may change in a shorter period of time. The referral to a gastroenterologist/hepatologist was determined by the stop codes used in the VA for such visits, and the liver biopsy rates were determined based on ICD-9 and CPT procedure codes. Events may have been missed if they were not coded appropriately, or if such referrals/procedures were performed outside the VA healthcare system. We limited our final dataset to subjects who had HCV RNA as well as AST/ALT levels, since they are prerequisites in determining treatment eligibility. Only about one-third of the subjects had these laboratory values recorded. We compared the demographics of the evaluable dataset with those that were excluded, and also compared the rates of various contraindications in all subjects with diagnosis based on ICD-9 codes. The results were generally comparable in those groups, strongly suggesting that our reported data represent the overall HCV-infected veterans. Antiretroviral therapy in the HIV-coinfected group can lead to liver enzyme elevations, and this was not studied.
It is important to note that the time frame for our study was 1998–2003. In the past few years, treatment rates may have improved due to increased awareness on the part of both patients and providers, and a better understanding and management of drug-related toxicities. Although we have reported treatment prescription rates in our study, this was not its focus. Subsequent studies to determine such rates in a more recent cohort will be undertaken in the future.
In summary, most veterans with HCV are ineligible for treatment according to the current guidelines, even when they have indications for treatment. HCV-HIV-coinfected veterans are even more likely to be ineligible. Even when veterans were eligible for treatment, only a small proportion ever received any treatment. Several contraindications to treatment are potentially modifiable, and aggressive management of those may lead to better treatment prescription rates.