Abstract
Hepatitis B (HBV) and hepatitis C (HCV) co-infection are increasingly important sources of morbidity among HIV-infected persons. We determined associations between hepatitis co-infection and healthcare utilization among HIV-infected adults at four U.S. sites during 2006–2011. Outpatient HIV visits did not differ by hepatitis serostatus and decreased over time. Mental health visits were more common among HIV/HCV co-infected persons than among HIV mono-infected (IRR 1.27 [1.08–1.50]). Hospitalization rates were higher among all hepatitis-infected groups than among HIV mono-infected (HIV/HBV IRR 1.23 [1.05–1.44], HIV/HCV 1.22 [1.10–1.36], HIV/HBV/HCV 1.31 [1.02–1.68]). These findings may inform the design of clinical services and allocation of resources.
Keywords: HIV, hepatitis B virus, hepatitis C virus, mental health, healthcare utilization, hospitalization
INTRODUCTION
With the passage of the Patient Protection and Affordable Care Act (ACA), persons living with HIV (PLWH) in the United States can expect healthcare changes that include expansion of insurance coverage, removal of lifetime coverage caps, shifting of resources to community health centers, and incentives to improve care coordination.1 Updated reports of healthcare utilization by PLWH are needed to understand the healthcare needs of this population and plan for changes.
In the U.S., 5–10% of PLWH are co-infected with hepatitis B virus (HBV) and 20–33% with hepatitis C virus (HCV).2–13 Co-infected patients are at risk of hepatic and extrahepatic complications.13–23 Viral hepatitis has emerged as a leading cause of morbidity and mortality among PLWH.24,25 We hypothesized that healthcare utilization among PLWH might differ according to hepatitis serostatus.
The purpose of this study is to characterize the impact of hepatitis co-infection on utilization of primary HIV care, mental health, and inpatient services in a multi-site, multi-state cohort of PLWH.
METHODS
Site Selection and Data Collection
The HIV Research Network (HIVRN) is a consortium of HIV care sites in 11 U.S. cities. Demographic, laboratory, and treatment data are abstracted from clinical records, de-identified, and consolidated into a uniform database. All sites routinely report primary HIV care visits; four also reported mental health and inpatient visits by adult participants from January 1, 2006, through December 31, 2011, and are therefore included in this analysis.
Participants in this analysis were engaged in care during ≥1 year in the study period, as defined by having ≥1 primary HIV care visit, CD4 count, and HIV-1 RNA. The unit of analysis was the patient-year (PY). Institutional review boards at each site and the data coordinating center approved the collection and use of these data for analysis and publication.
Definitions of Variables
Hepatitis serostatus was assessed using HBV surface antigen and HCV antibody. Positive results within six months of enrollment and all negative results were carried backward. Results before July 1 were used to categorize hepatitis serostatus from that year onward, while results after July 1 were used only for subsequent years. Data were censored at the time of death, loss to follow-up, or end of study.
Clinical and demographic characteristics were assessed using previously-published definitions as summarized in Table 1.26 Time-dependent variables included age, CD4, HIV-1 RNA, ART and insurance status. Race/ethnicity, gender and HIV transmission risk factor were categorized by self-report. For secondary analyses, FIB-4 score and use of ART with HBV activity were also considered time-dependent.27
Table 1.
Population Demographic and Clinical Characteristics at Study Entry
| Characteristic | HIV Mono-infected n=9,146 (%) |
HIV/HBV Co-infected n=536 (%) |
HIV/HCV Co-infected n=2,056 (%) |
HIV/HBV/HCV Tri-infected n=115 (%) |
Unknown Serostatus n=4,074 (%) |
|---|---|---|---|---|---|
| Age [years]* | |||||
| Median (IQR) | 40.4 (32.6–47.0) | 41.2 (35.3–46.8) | 47.0 (42.0–51.9) | 45.4 (41.2–50.7) | 43.0 (35.2–49.4) |
| 18 – 34 | 2856 (31.2) | 127 (23.7) | 154 (7.5) | 6 (5.2) | 996 (24.4) |
| 35 – 49 | 4738 (51.8) | 325 (60.6) | 1167 (56.8) | 79 (68.7) | 2154 (52.9) |
| 50 – 64 | 1420 (15.5) | 80 (14.9) | 720 (35.0) | 30 (26.1) | 855 (21) |
| ≥ 65 | 132 (1.4) | 4 (0.8) | 15 (0.7) | 0 (0) | 69 (1.7) |
| Race/Ethnicity | |||||
| White | 3180 (34.8) | 202 (37.7) | 627 (30.5) | 34 (29.6) | 1637 (40.2) |
| Black | 3750 (41.0) | 252 (47.0) | 1247 (60.6) | 75 (65.2) | 1611 (39.5) |
| Hispanic | 1907 (20.8) | 61 (11.4) | 154 (7.5) | 4 (3.5) | 692 (17.0) |
| Other/Unknown | 309 (3.4) | 21 (3.9) | 28 (1.4) | 2 (1.7) | 134 (3.3) |
| Gender | |||||
| Male | 6929 (75.8) | 488 (91.0) | 1468 (71.4) | 96 (83.5) | 3255 (79.9) |
| Female | 2217 (24.2) | 48 (9.0) | 588 (28.6) | 19 (16.5) | 819 (20.1) |
| HIV risk factor | |||||
| Heterosexual | 3475 (38.0) | 124 (23.1) | 384 (18.7) | 14 (12.2) | 1180 (29.0) |
| MSM† | 4807 (52.6) | 359 (67.0) | 357 (17.4) | 26 (22.6) | 1936 (47.5) |
| IDU‡ | 519 (5.7) | 34 (6.3) | 1251 (60.8) | 73 (63.5) | 776 (19.0) |
| Other/Unknown | 342 (3.7) | 19 (3.5) | 64 (3.1) | 2 (1.7) | 182 (4.5) |
| CD4 count (cells/mm3)# | |||||
| Median (IQR) | 357 (175–549) | 300 (106–504) | 321 (155–528) | 247 (95–415) | 383 (212–567) |
| ≤50 | 1050 (11.5) | 94 (17.5) | 212 (10.3) | 18 (15.6) | 331 (8.1) |
| 51–200 | 1510 (16.5) | 112 (20.9) | 428 (20.8) | 32 (27.8) | 625 (15.3) |
| 201–500 | 3813 (41.7) | 194 (36.2) | 857 (41.7) | 45 (39.1) | 1760 (43.2) |
| >500 | 2773 (30.3) | 136 (25.4) | 559 (27.2) | 20 (17.4) | 1358 (33.3) |
| HIV-1 RNA (copies/mL)# | |||||
| Median (IQR) | 4326(UND-84200) | 9465(UND-99138) | 2293(UND-56350) | 2650(UND-90563) | 898(UND-49700) |
| <400 | 2837 (31.0) | 170 (31.7) | 701 (34.1) | 41 (35.6) | 1364 (33.5) |
| ≥ 400 | 6309 (69.0) | 366 (68.3) | 1355 (65.9) | 74 (64.4) | 2710 (66.5) |
| ART§ | |||||
| No | 2163 (23.6) | 100 (18.7) | 542 (26.4) | 21 (18.3) | 966 (23.7) |
| Yes | 6983 (76.4) | 436 (81.3) | 1514 (73.6) | 94 (81.7) | 3108 (76.3) |
| With HBV activity | 4615 (66.1) | 306 (70.2) | 1007 (66.5) | 63 (67.0) | 1857 (59.8) |
| Insurance# | |||||
| Medicaid | 1307 (14.3) | 81 (15.1) | 721 (35.1) | 41 (35.6) | 684 (16.8) |
| Medicare/Dual eligible | 1556 (17.0) | 104 (19.4) | 386 (18.8) | 33 (28.7) | 827 (20.3) |
| Private | 1345 (14.7) | 81 (15.1) | 129 (6.3) | 6 (5.2) | 538 (13.2) |
| Ryan White/Uninsured | 4796 (52.4) | 263 (49.1) | 789 (38.4) | 35 (30.4) | 1945 (47.7) |
| Unknown/Missing | 142 (1.6) | 7 (1.3) | 31 (1.5) | 0 (0) | 80 (2.0) |
| Year of study entry | |||||
| 2006 | 4500 (49.2) | 235 (43.8) | 1110 (54.0) | 66 (57.4) | 2000 (49.1) |
| 2007 | 959 (10.5) | 79 (14.7) | 257 (12.5) | 16 (13.9) | 422 (10.4) |
| 2008 | 955 (10.4) | 62 (11.6) | 253 (12.3) | 14 (12.2) | 236 (5.8) |
| 2009 | 969 (10.6) | 56 (10.4) | 187 (9.1) | 9 (7.8) | 253 (6.2) |
| 2010 | 1005 (11.0) | 63 (11.8) | 163 (7.9) | 7 (6.1) | 475 (11.7) |
| 2011 | 758 (8.3) | 41 (7.6) | 86 (4.2) | 3 (2.6) | 688 (16.9) |
| Status at end of study | |||||
| Alive | 8585 (93.9) | 471 (87.9) | 1748 (85.0) | 86 (74.8) | 3755 (92.2) |
| Deceased | 561 (6.2) | 65 (12.1) | 308 (15.0) | 29 (25.2) | 319 (7.8) |
Age was assessed on July 1 of the year of study entry.
Patients who reported sex with both men and women were categorized as MSM.
Patients who reported IDU in addition to any other risk factor were categorized as IDU.
CD4, HIV-1 RNA, and insurance data are the first available for the calendar year of study entry. UND: undetectable
ART refers to concurrent use of ≥3 antiretroviral medications from ≥2 classes at any time during the calendar year of study entry. HBV activity is defined by an ART regimen that contains tenofovir, lamivudine, or emtricitabine; percentages with HBV activity reflect the number prescribed one or more of these agents divided by the number prescribed ART in each hepatitis serostatus category.
Outcomes
Primary HIV care visits were defined as visits to an HIV care provider, not including visits to nurses or subspecialists within multidisciplinary HIV clinics. Mental health visits were visits to a psychologist, psychiatrist or other mental health provider, not including visits to substance abuse treatment programs such as methadone clinics. Any non-hospice acute care inpatient visit was included. Mortality was assessed by local study staff report.
Data Analysis
Unadjusted healthcare utilization rates were calculated using total number of visits as the numerator and aggregate person-time as the denominator. Person-time was accrued daily as a fraction of each calendar year, so participants contributed <1 year of observation during the year of enrollment or death.
Number of primary HIV care, mental health, and inpatient visits were modeled using negative binomial regression to estimate incidence rate ratios (IRRs). Age, race/ethnicity, gender, HIV risk factor, CD4, HIV-1 RNA, ART, and insurance status were pre-specified covariates of interest. Multivariable models also included categorical indicators for clinical care site to control for site-specific variability and indicators for calendar year to control for secular trends. Several secondary analyses were performed including, 1) adding number of primary HIV care visits as a predictor for mental health and inpatient visits; 2) evaluating the effects of FIB-4 score and use of ART with HBV activity (tenofovir, lamivudine, or emtricitabine) among subjects with any hepatitis and with HBV co-infection, respectively; and 3) investigating mortality using logistic regression with variables from the primary models.
To account for multiple observations involving the same individual, all models used generalized estimating equations, clustered on patient, with exchangeable working correlation and robust variance estimators. A two-sided type I error of 5% was considered statistically significant. All analyses were performed using Stata 12.0 (StataCorp LP, College Station, TX, USA).
RESULTS
Demographic and Clinical Characteristics
A total of 15,927 participants contributed 49,061 person-years of observation time. At study entry, 9,146 individuals (57.4%) had HIV mono-infection; 536 (3.4%) HIV/HBV; 2,056 (12.9%) HIV/HCV; 115 (0.7%) HIV/HBV/HCV; and 4,074 (25.6%) unknown hepatitis serostatus (Table 1). Of those with initially unknown serostatus, 89 participants later contributed person-time to the HIV/HBV co-infected group, 365 HIV/HCV co-infected, and 26 HIV/HBV/HCV tri-infected. The median age ranged from 40.4 years (IQR 32.6–47.0) in the HIV mono-infected group to 47.0 (42.0–51.9) years in the HIV/HCV co-infected group. There were higher proportions of male patients in the HIV/HBV (91.0%) and HIV/HBV/HCV groups (83.5%) than in the other hepatitis serostatus groups. IDU was reported in 5.7% of HIV mono-infected and 6.3% of HIV/HBV co-infected patients, but was reported in 60.8% of HIV/HCV and 63.5% of HIV/HBV/HCV patients.
Healthcare Utilization and Serostatus
A total of 227,618 primary HIV care visits, 24,415 mental health visits and 13,761 inpatient visits were observed. Primary HIV care visit rates were similar across all hepatitis serostatus categories, with an average across time for the full study cohort of 4.64 visits/PY (Supplemental Digital Content Table 1). Over the five-year study period, 23.0% of participants had at least one mental health visit, including 21.2% of HIV mono-infected, 21.2% of HIV/HBV co-infected, 34.9% of HIV/HCV co-infected, 30.7% of HIV/HBV/HCV tri-infected and 18.3% of patients with unknown hepatitis serostatus (Supplemental Digital Content Table 2). Among all participants, 33.0% experienced ≥1 inpatient visits during the study period, including 31.6% of those with HIV mono-infection, 37.7% with HIV/HBV co-infection, 46.2% HIV/HCV co-infection, 49.3% HIV/HBV/HCV tri-infection and 24.6% unknown hepatitis serostatus.
In multivariable analysis, there was no association between hepatitis serostatus and number of primary HIV care visits (Table 2). Compared to the HIV mono-infected group, patients with HIV/HCV co-infection had significantly higher mental health utilization rates (IRR 1.27 [95% CI 1.08–1.50]). Inpatient utilization was higher in all hepatitis co-infected groups than with HIV mono-infection (HIV/HBV 1.23 [1.05–1.44], HIV/HCV 1.22 [1.10–1.36], HIV/HBV/HCV 1.31 [1.02–1.68]). Non-White race/ethnicity was a predictor of decreased mental health utilization as compared to White race/ethnicity. Age >50 years was associated with more primary HIV visits; age 35–64 with more mental health visits and age ≥65 with more hospitalizations. Private insurance was associated with lower primary HIV, mental health, and inpatient utilization, as compared to Medicaid, Medicare, and Ryan White/Uninsured.
Table 2.
Multivariable Analysis of Risk Factors for Healthcare Utilization
| Characteristic | Primary HIV CareVisits IRR (95% CI) |
Mental Health Visits IRR (95% CI) |
InpatientVisits IRR (95% CI) |
|---|---|---|---|
| Hepatitis Serostatus | |||
| HIV mono-infection | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| HIV/HBV co-infection | 1.02 (0.97–1.07) | 0.86 (0.69–1.06) | 1.23 (1.05–1.44) |
| HIV/HCV co-infection | 1.02 (0.99–1.05) | 1.27 (1.08–1.50) | 1.22 (1.10–1.36) |
| HIV/HBV/HCV tri-infection | 0.93 (0.86–1.00) | 0.82 (0.57–1.18) | 1.31 (1.02–1.68) |
| Unknown serostatus | 1.01 (0.99–1.03) | 1.24 (1.03–1.48) | 0.93 (0.85–1.03) |
| Age (years)* | |||
| 18 – 34 | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| 35 – 49 | 0.94 (0.92–0.96) | 1.26 (1.05–1.50) | 0.94 (0.86–1.02) |
| 50 – 64 | 1.03 (1.00–1.06) | 1.34 (1.10–1.64) | 1.08 (0.97–1.20) |
| ≥ 65 | 1.08 (1.02–1.15) | 1.08 (0.76–1.53) | 1.49 (1.21–1.83) |
| Race/Ethnicity | |||
| White | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| Black | 1.04 (1.01–1.06) | 0.60 (0.53–0.69) | 1.07 (0.98–1.17) |
| Hispanic | 1.04 (1.01–1.07) | 0.50 (0.41–0.60) | 1.03 (0.93–1.15) |
| Other/Unknown | 0.98 (0.93–1.04) | 0.47 (0.33–0.68) | 0.77 (0.58–1.02) |
| Gender | |||
| Male | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| Female | 1.09 (1.07–1.12) | 1.54 (1.29–1.84) | 1.16 (1.06–1.26) |
| HIV risk factor | |||
| Heterosexual | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| MSM† | 1.02 (1.00–1.05) | 1.65 (1.41–1.93) | 0.90 (0.82–1.00) |
| IDU‡ | 1.04 (1.01–1.08) | 1.49 (1.24–1.79) | 1.28 (1.14–1.43) |
| Other/Unknown | 0.98 (0.93–1.04) | 1.34 (0.58–3.10) | 1.54 (1.27–1.87) |
| CD4 count (cells/mm3)# | |||
| >500 | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| 201–500 | 1.07 (1.05–1.08) | 0.96 (0.88–1.04) | 1.53 (1.41–1.65) |
| 51–200 | 1.20 (1.18–1.23) | 0.95 (0.83–1.08) | 3.15 (2.86–3.47) |
| ≤ 50 | 1.49 (1.44–1.54) | 0.80 (0.67–0.95) | 7.49 (6.79–8.26) |
| HIV-1 RNA (copies/mL)# | |||
| <400 | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| ≥400 | 1.21 (1.19–1.22) | 1.09 (1.00–1.18) | 1.71 (1.60–1.82) |
| ART§ | |||
| No | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| Yes | 1.20 (1.18–1.23) | 1.10 (0.97–1.25) | 0.94 (0.86–1.03) |
| Insurance# | |||
| Private | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| Medicaid | 1.17 (1.13–1.20) | 1.66 (1.42–1.94) | 1.82 (1.60–2.07) |
| Medicare/Dual eligible | 1.16 (1.13–1.19) | 1.46 (1.24–1.72) | 1.75 (1.53–2.01) |
| Ryan White/Uninsured | 1.22 (1.19–1.25) | 1.63 (1.36–1.95) | 1.21 (1.07–1.38) |
| Unknown/Missing | 0.69 (0.66–0.72) | 0.70 (0.55–0.88) | 0.65 (0.50–0.85) |
| Year | |||
| 2006 | 1.0 (REF) | 1.0 (REF) | 1.0 (REF) |
| 2007 | 0.93 (0.91–0.95) | 1.07 (0.98–1.16) | 1.14 (1.05–1.24) |
| 2008 | 0.93 (0.91–0.94) | 1.12 (1.01–1.24) | 1.05 (0.97–1.14) |
| 2009 | 0.93 (0.92–0.95) | 0.90 (0.82–0.99) | 1.20 (1.11–1.31) |
| 2010 | 0.93 (0.91–0.95) | 0.71 (0.64–0.79) | 1.17 (1.07–1.27) |
| 2011 | 0.85 (0.83–0.87) | 0.66 (0.60–0.73) | 1.06 (0.96–1.16) |
Age was assessed annually on July 1.
Patients who reported sex with both men and women were categorized as MSM.
Patients who reported IDU in addition to any other risk factor were categorized as IDU.
CD4, HIV-1 RNA, and insurance data are the first available for each year.
ART refers to concurrent use of ≥3 antiretroviral medications from ≥2 classes at any time during the calendar year.
The unit of analysis for all models was person-year. Incidence rate ratios (IRRs) are interpreted as the relative number of visits compared to the reference group after adjusting for other listed characteristics and clinical care site. Statistically significant results (p≤0.05) are shown in bold.
Healthcare Utilization Over Time
Across all hepatitis serostatus groups, primary HIV care visits ranged from 4.5–5.5 visits/PY in 2006 and decreased to 4.0–4.6 visits/PY in 2011 (unadjusted P for decreasing trend < 0.01 for most hepatitis serostatus groups, Supplemental Digital Content Figure 1). Mental health utilization decreased from 42.1–116.7 visits/100 PY in 2006 to 21.5–67.7 visits/100 PY in 2011, with significant declines in all hepatitis serostatus groups except unknown. There were statistically significant decreases in unadjusted inpatient utilization across all groups except HIV/HBV/HCV tri-infection and unknown serostatus, from 24.2–72.4 visits/100 PY in 2006 to 19.8–34.1 visits/100 PY in 2011. In multivariable analysis, however, inpatient utilization did not decline across time for the full sample (Table 2) or for any hepatitis serostatus subgroup (Supplemental Digital Content Figure 1).
Secondary Analyses
When compared to 1–3 visits/year, increasing HIV primary care utilization was independently associated with increased mental health (4–6 visits/year IRR 1.52 [1.41–1.64], ≥7 visits/year 2.56 [2.34–2.80]) and inpatient (4–6 visits/year 1.22 [1.15–1.30], ≥7 visits/year 2.43 [2.26–2.61]) utilization. When controlling for primary HIV care visits, inferences about hepatitis serostatus and healthcare utilization were unchanged.
Among subjects with any hepatitis co-infection, increased FIB-4 score was associated with more HIV primary care visits (FIB-4 ≥3.25 IRR 1.08 [1.03–1.13], as compared to <1.45) and inpatient admissions (1.95 [1.76–2.16]), but no difference in mental health visits (0.96 [0.78–1.19]). Among subjects with HBV co-infection, use of ART with HBV activity was associated with significantly fewer outpatient HIV primary care visits (0.83 [0.73–0.95]) and a trend towards fewer inpatient admissions (0.71 [0.48–1.05]), as compared to use of ART without HBV activity and after controlling for other covariates. With few observations, the model for mental health utilization did not converge when adjusting for use of ART with HBV activity.
In multivariable analysis, mortality was higher in all hepatitis co-infected groups than with HIV mono-infection (HIV/HBV 1.91 [1.39–2.62], HIV/HCV 1.30 [1.05–1.62], HIV/HBV/HCV 2.56 [1.70–3.85]).
DISCUSSION
Our study makes several important observations about healthcare utilization among PLWH. First, there was no difference in primary HIV care utilization according to hepatitis serostatus. Second, patients with HIV/HCV co-infection demonstrated higher rates of mental health visits than any of the other groups examined. Finally, rates of inpatient utilization were elevated across all hepatitis-infected categories as compared to HIV mono-infection.
Hepatitis co-infection was not associated with increased utilization of primary HIV care. It is possible that PLWH who are co-infected with viral hepatitis have differences in utilization of other subspecialty services, such as gastroenterology or hepatology, but data regarding subspecialty referrals were not available and further investigation is warranted. Decreasing utilization of primary HIV care services over time may be attributable to evolving guideline recommendations for less frequent monitoring for patients with well-controlled HIV disease.28–30
HIV/HCV co-infected participants utilized more outpatient mental health services than any other hepatitis serostatus group. Prior studies have reported that 3.2–8.8% of the general U.S. population presents for ≥1 mental health visit per year.31,32 In our study, 12.5–16.0% of PLWH utilized mental health services during each calendar year, underscoring the high burden of mental illness among PLWH. As in the general U.S. population, non-White PLWH were less likely to utilize mental health services than were those self-reporting White race/ethnicity, potentially reflecting cultural barriers to care or other access issues.33 Healthcare delivery systems caring for PLWH must be prepared to handle a high demand for mental health services, particularly among HIV/HCV co-infected patients.
We have previously shown that hepatitis co-infection was associated with increased inpatient utilization during a single year (2010), and here we demonstrate that this relationship has persisted over time.26 The association between higher FIB-4 score and increased hospitalization rates suggests that hepatocellular dysfunction may directly contribute to the risk of hospitalization in co-infected patients. Use of ART with activity against HBV by persons with HBV co-infection may attenuate the risk of hospitalization.
This study has several potential limitations. First, we relied on HCV antibodies as an indirect marker of HCV co-infection, since HCV RNA levels were not available. However, spontaneous clearance of HCV occurs in less than 10% of PLWH.34 The impact of HCV therapy was not evaluated, but prior studies have reported low treatment rates in the routine care of co-infected PLWH.35–37 Substance abuse is associated with both psychiatric disease and HIV/HCV co-infection, so it is possible that substance abuse contributes to differences in mental health utilization. Treatment of drug addiction was not assessed, but may play a particularly important role in the management of HIV/HCV co-infected patients. HIV/HCV co-infected patients tended to be older than patients in other hepatitis serostatus groups. While all multivariable models included age, residual confounding may have contributed to the differences observed between groups. Lower healthcare utilization among the privately insured raises the possibility that financial differences across groups, such as variable influences of lost work time, may have contributed to some of our observations. Finally, hepatitis serostatus data were not available for all participants, potentially introducing bias if there has been differential failure to capture this information.
Chronic viral hepatitis is associated with differences in mental health and inpatient utilization among PLWH, but not primary HIV care visits. Decreases in primary HIV care utilization over time among all PLWH likely reflect shifting treatment paradigms. Third-party payers and policy-makers should be aware of the high mental health service utilization by patients with HIV/HCV co-infection and heightened risk of hospitalization among PLWH with any hepatitis co-infection as they design healthcare delivery systems and allocate limited healthcare resources.
Supplementary Material
Acknowledgments
HIVRN Participating Sites
Alameda County Medical Center, Oakland, California (Howard Edelstein, M.D.)
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania (Richard Rutstein, M.D.)
Community Health Network, Rochester, New York (Roberto Corales, D.O.)
Drexel University, Philadelphia, Pennsylvania (Jeffrey Jacobson, M.D., Sara Allen, C.R.N.P.)
Fenway Health, Boston, Massachusetts (Stephen Boswell, M.D.)
Johns Hopkins University, Baltimore, Maryland (Kelly Gebo, M.D., Richard Moore, M.D., Allison Agwu M.D.)
Montefiore Medical Group, Bronx, New York (Robert Beil, M.D.)
Montefiore Medical Center, Bronx, New York (Lawrence Hanau, M.D.)
Oregon Health and Science University, Portland, Oregon (P. Todd Korthuis, M.D.)
Parkland Health and Hospital System, Dallas, Texas (Ank Nijhawan, M.D., Muhammad Akbar, M.D.)
St. Jude’s Children’s Hospital and University of Tennessee, Memphis, Tennessee (Aditya Gaur, M.D.)
St. Luke’s Roosevelt Hospital Center, New York, New York (Victoria Sharp, M.D., Stephen Arpadi, M.D.)
Tampa General Health Care, Tampa, Florida (Charurut Somboonwit, M.D.)
University of California, San Diego, California (W. Christopher Mathews, M.D.)
Sponsoring Agencies
Agency for Healthcare Research and Quality, Rockville, Maryland (Fred Hellinger, Ph.D., John Fleishman, Ph.D., Irene Fraser, Ph.D.)
Health Resources and Services Administration, Rockville, Maryland (Robert Mills, Ph.D., Faye Malitz, M.S.)
Data Coordinating Center
Johns Hopkins University (Richard Moore, M.D., Jeanne Keruly, C.R.N.P., Kelly Gebo, M.D., Cindy Voss, M.A., Nikki Balding, M.S.)
Source of Funding: This work was supported by the Agency for Healthcare Research and Quality (HHSA290201100007C), the Health Resources and Services Administration (HHSH250201200008C), the National Institute of Allergy and Infectious Diseases (K23 AI084854), and the National Center for Advancing Translational Sciences (KL2TR001103).
Footnotes
Prior Presentation: This research was presented, in part, at IDWeek 2013, San Francisco, CA, 5 October 2013.
Conflicts of Interest: The author K.A.G. has been a consultant to Tibotec and BMS and received research funding from Tibotec. The other authors report no conflicts of interest.
Publisher's Disclaimer: Disclaimer: The views expressed in this paper are those of the authors. No official endorsement by DHHS, the National Institutes of Health, or the Agency for Healthcare Research and Quality is intended or should be inferred.
References
- 1.Martin EG, Schackman BR. What does U.S. health reform mean for HIV clinical care? Journal of acquired immune deficiency syndromes. 2012 May 1;60(1):72–76. doi: 10.1097/QAI.0b013e31824c0dd4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Konopnicki D, Mocroft A, de Wit S, et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. Aids. 2005 Mar 24;19(6):593–601. doi: 10.1097/01.aids.0000163936.99401.fe. [DOI] [PubMed] [Google Scholar]
- 3.Thomas DL, Leoutsakas D, Zabransky T, Kumar MS. Hepatitis C in HIV-infected individuals: cure and control, right now. Journal of the International AIDS Society. 2011;14:22. doi: 10.1186/1758-2652-14-22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Weber R, Sabin C, Reiss P, et al. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study. Antiviral therapy. 2010;15(8):1077–1086. doi: 10.3851/IMP1681. [DOI] [PubMed] [Google Scholar]
- 5.Thio CL, Seaberg EC, Skolasky R, Jr, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS) Lancet. 2002 Dec 14;360(9349):1921–1926. doi: 10.1016/s0140-6736(02)11913-1. [DOI] [PubMed] [Google Scholar]
- 6.Arribas JR, Gonzalez-Garcia JJ, Lorenzo A, et al. Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain. Aids. 2005 Sep 2;19(13):1361–1365. doi: 10.1097/01.aids.0000180787.10553.b2. [DOI] [PubMed] [Google Scholar]
- 7.Bonacini M, Louie S, Bzowej N, Wohl AR. Survival in patients with HIV infection and viral hepatitis B or C: a cohort study. Aids. 2004 Oct 21;18(15):2039–2045. doi: 10.1097/00002030-200410210-00008. [DOI] [PubMed] [Google Scholar]
- 8.De Luca A, Bugarini R, Lepri AC, et al. Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naive HIV-infected subjects. Archives of internal medicine. 2002 Oct 14;162(18):2125–2132. doi: 10.1001/archinte.162.18.2125. [DOI] [PubMed] [Google Scholar]
- 9.den Brinker M, Wit FW, Wertheim-van Dillen PM, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. Aids. 2000 Dec 22;14(18):2895–2902. doi: 10.1097/00002030-200012220-00011. [DOI] [PubMed] [Google Scholar]
- 10.Kim JH, Psevdos G, Suh J, Sharp VL. Co-infection of hepatitis B and hepatitis C virus in human immunodeficiency virus-infected patients in New York City, United States. World journal of gastroenterology : WJG. 2008 Nov 21;14(43):6689–6693. doi: 10.3748/wjg.14.6689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Sollima S, Caramma I, Menzaghi B, et al. Chronic coinfection with hepatitis B and hepatitis C viruses in an Italian population of HIV-infected patients. Journal of acquired immune deficiency syndromes. 2007 Apr 15;44(5):606–607. doi: 10.1097/QAI.0b013e318031d5b5. [DOI] [PubMed] [Google Scholar]
- 12.Lincoln D, Petoumenos K, Dore GJ, Australian HIVOD HIV/HBV and HIV/HCV coinfection, and outcomes following highly active antiretroviral therapy. HIV medicine. 2003 Jul;4(3):241–249. doi: 10.1046/j.1468-1293.2003.00152.x. [DOI] [PubMed] [Google Scholar]
- 13.Castellares C, Barreiro P, Martin-Carbonero L, et al. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. Journal of viral hepatitis. 2008 Mar;15(3):165–172. doi: 10.1111/j.1365-2893.2007.00903.x. [DOI] [PubMed] [Google Scholar]
- 14.Lee MH, Yang HI, Lu SN, et al. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. The Journal of infectious diseases. 2012 Aug 15;206(4):469–477. doi: 10.1093/infdis/jis385. [DOI] [PubMed] [Google Scholar]
- 15.Bedimo R, Westfall AO, Mugavero M, Drechsler H, Khanna N, Saag M. Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients. HIV medicine. 2010 Aug;11(7):462–468. doi: 10.1111/j.1468-1293.2009.00815.x. [DOI] [PubMed] [Google Scholar]
- 16.Satapathy SK, Lingisetty CS, Williams S. Higher prevalence of chronic kidney disease and shorter renal survival in patients with chronic hepatitis C virus infection. Hepatology international. 2011 Jun 23; doi: 10.1007/s12072-011-9284-9. [DOI] [PubMed] [Google Scholar]
- 17.Naing C, Mak JW, Ahmed SI, Maung M. Relationship between hepatitis C virus infection and type 2 diabetes mellitus: meta-analysis. World journal of gastroenterology : WJG. 2012 Apr 14;18(14):1642–1651. doi: 10.3748/wjg.v18.i14.1642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Clifford DB, Evans SR, Yang Y, Gulick RM. The neuropsychological and neurological impact of hepatitis C virus co-infection in HIV-infected subjects. Aids. 2005 Oct;19(Suppl 3):S64–71. doi: 10.1097/01.aids.0000192072.80572.43. [DOI] [PubMed] [Google Scholar]
- 19.Brau N, Fox RK, Xiao P, et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study. Journal of hepatology. 2007 Oct;47(4):527–537. doi: 10.1016/j.jhep.2007.06.010. [DOI] [PubMed] [Google Scholar]
- 20.Gebo KA, Diener-West M, Moore RD. Hospitalization rates differ by hepatitis C satus in an urban HIV cohort. J Acquir Immune Defic Syndr. 2003 Oct 1;34(2):165–173. doi: 10.1097/00126334-200310010-00006. [DOI] [PubMed] [Google Scholar]
- 21.Goedert JJ, Eyster ME, Lederman MM, et al. End-stage liver disease in persons with hemophilia and transfusion-associated infections. Blood. 2002 Sep 1;100(5):1584–1589. [PubMed] [Google Scholar]
- 22.Puoti M, Torti C, Bruno R, Filice G, Carosi G. Natural history of chronic hepatitis B in co-infected patients. Journal of hepatology. 2006;44(1 Suppl):S65–70. doi: 10.1016/j.jhep.2005.11.015. [DOI] [PubMed] [Google Scholar]
- 23.Salmon-Ceron D, Rosenthal E, Lewden C, et al. Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalite 2005 study. Journal of hepatology. 2009 Apr;50(4):736–745. doi: 10.1016/j.jhep.2008.11.018. [DOI] [PubMed] [Google Scholar]
- 24.Smith C, Sabin CA, Lundgren JD, et al. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study. Aids. 2010 Jun 19;24(10):1537–1548. doi: 10.1097/QAD.0b013e32833a0918. [DOI] [PubMed] [Google Scholar]
- 25.Palella FJ, Jr, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. Journal of acquired immune deficiency syndromes. 2006 Sep;43(1):27–34. doi: 10.1097/01.qai.0000233310.90484.16. [DOI] [PubMed] [Google Scholar]
- 26.Crowell TA, Gebo KA, Balagopal A, Fleishman JA, Agwu AL, Berry SA. Impact of Hepatitis Coinfection on Hospitalization Rates and Causes in a Multicenter Cohort of Persons Living With HIV. Journal of acquired immune deficiency syndromes. 2014 Apr 1;65(4):429–437. doi: 10.1097/QAI.0000000000000059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317–1325. doi: 10.1002/hep.21178. [DOI] [PubMed] [Google Scholar]
- 28.Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2013 http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed 28 October 2013.
- 29.Gale HB, Gitterman SR, Hoffman HJ, et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/muL and HIV-1 suppression? Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013 May;56(9):1340–1343. doi: 10.1093/cid/cit004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013 Nov 13; doi: 10.1093/cid/cit757. [DOI] [PubMed] [Google Scholar]
- 31.Olfson M, Marcus SC. National trends in outpatient psychotherapy. The American journal of psychiatry. 2010 Dec;167(12):1456–1463. doi: 10.1176/appi.ajp.2010.10040570. [DOI] [PubMed] [Google Scholar]
- 32.Wang PS, Lane M, Olfson M, Pincus HA, Wells KB, Kessler RC. Twelve-month use of mental health services in the United States: results from the National Comorbidity Survey Replication. Archives of general psychiatry. 2005 Jun;62(6):629–640. doi: 10.1001/archpsyc.62.6.629. [DOI] [PubMed] [Google Scholar]
- 33.Alegria M, Chatterji P, Wells K, et al. Disparity in depression treatment among racial and ethnic minority populations in the United States. Psychiatr Serv. 2008 Nov;59(11):1264–1272. doi: 10.1176/appi.ps.59.11.1264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA : the journal of the American Medical Association. 2000 Jul 26;284(4):450–456. doi: 10.1001/jama.284.4.450. [DOI] [PubMed] [Google Scholar]
- 35.Reiberger T, Obermeier M, Payer BA, et al. Considerable under-treatment of chronic HCV infection in HIV patients despite acceptable sustained virological response rates in a real-life setting. Antiviral therapy. 2011;16(6):815–824. doi: 10.3851/IMP1831. [DOI] [PubMed] [Google Scholar]
- 36.Scott JD, Wald A, Kitahata M, et al. Hepatitis C virus is infrequently evaluated and treated in an urban HIV clinic population. AIDS patient care and STDs. 2009 Nov;23(11):925–929. doi: 10.1089/apc.2009.0099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Vellozzi C, Buchacz K, Baker R, et al. Treatment of hepatitis C virus (HCV) infection in patients coinfected with HIV in the HIV Outpatient Study (HOPS), 1999–2007. Journal of viral hepatitis. 2011 May;18(5):316–324. doi: 10.1111/j.1365-2893.2010.01299.x. [DOI] [PubMed] [Google Scholar]
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