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Prevalence of Human Immunodeficiency Virus Testing in Patients With Hepatitis B and C Infection
Mayo Clin Proc, January 2004, Vol 79
HIV Testing in Hepatitis Patients
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Original Article
Prevalence of Human Immunodeficiency Virus Testing in Patients With Hepatitis B and C Infection ALYSA KRAIN, MD, MSC; JUAN P. WISNIVESKY, MD; ELIZABETH GARLAND, MD, MS; AND THOMAS MCGINN, MD, MPH
• Objectives: To determine the proportion of patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) who are adequately assessed for human immunodeficiency virus (HIV) and to identify variables associated with absence of HIV testing. • Patients and Methods: We retrospectively reviewed the medical records of patients who had positive serologic test results for reactive HBV and/or HCV between January 1999 and December 1999 and were followed up at a general internal medicine clinic in East Harlem, NY. Data were collected on patient demographics, HIV risk factors, and other variables that might influence the physician’s decision to test the patient for HIV. Primary outcomes were HIV tests performed and documented discussions of at-risk HIV behavior. • Results: The HIV tests were performed in 40% (95% confidence interval [CI], 32%-49%) of the 141 patients with reactive HBV and/or HCV serologic test results. Predictors of HIV testing on multivariate logistic regression
were age younger than 50 years (odds ratio [OR], 2.5; 95% CI, 1.8-3.8), male sex (OR, 1.6; 95% CI, 1.1-2.2), and having an established primary care provider (OR, 2.3; 95% CI, 1.2-3.9). Injection drug use was not significantly associated with HIV testing. • Conclusions: Although HBV and HCV have clear epidemiological links with HIV, this study shows that a high percentage of these patients are not being tested. Although some of the factors associated with lack of testing were identified, further studies on the barriers to HIV testing are needed to reveal potential approaches to increase rates of HIV testing in this high-risk population. Mayo Clin Proc. 2004;79:51-56 AIDS = acquired immunodeficiency syndrome; CI = confidence interval; ELISA = enzyme-linked immunosorbent assay; HBcAb = hepatitis B core antibody; HBV = hepatitis B virus; HCV = hepatitis C virus; HCV Ab = hepatitis C virus antibody; HIV = human immunodeficiency virus; OR = odds ratio
H
epatitis B virus (HBV) and hepatitis C virus (HCV) are common, with 12.5 million and 3.9 million Americans having been exposed to HBV and HCV, respectively.1,2 Although human immunodeficiency virus (HIV) is less prevalent, the epidemiological features of HBV, HCV, and HIV make the incidence of coinfection likely.3-10 The prevalence of HBV and HCV infection has been well described in HIV cohorts; however, the epidemiological features are not well known.11-15 Despite multiple guidelines that indicate the need for HIV testing of patients who practice at-risk behaviors, missed opportunities exist.16 Estimates show that in 1998, approximately 250,000 people in the United States were unaware of their HIV diagnosis.17,18 This problem is espe-
cially serious among patients with HBV and/or HCV because delay in diagnosis may result in patients presenting not only with an advanced stage of acquired immunodeficiency syndrome (AIDS) but also with rapidly progressed viral hepatitis.19-24 Ultimately, these missed diagnoses may lead to worse patient outcomes and/or more complicated therapeutic decisions. Early diagnosis is even more important in light of recent data that show promising therapeutic interventions for HCV-HIV coinfected patients in the early stages of HIV disease (CD4 cell count, >500 × 106/L).25-31 The prevalence and predictors of HIV testing rates among patients with serologic exposure to viral hepatitis have not been studied previously. This information is important for developing strategies to improve the outcomes of these high-risk populations. The objective of this study was to determine the proportion of patients with HBV and HCV exposure who were adequately assessed for the presence of HIV and to identify variables associated with the absence of HIV testing when clinically indicated.
From the Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, NY (A.K.); and Division of General Internal Medicine (J.P.W., T.M.) and Department of Community and Preventive Medicine (E.G.), Mount Sinai Medical Center, New York, NY. Presented as a poster at the 24th Annual National Meeting of the Society of General Internal Medicine, San Diego, Calif, May 3-5, 2000.
PATIENTS AND METHODS The study was conducted at a general internal medicine clinic in East Harlem, NY, which serves approximately 14,000 patients per year. The ambulatory center is composed of 30 full-time attending physicians, 4 nurse practi-
Individual reprints of this article are not available. Address correspondence to Juan P. Wisnivesky, MD, Division of General Internal Medicine, Mount Sinai School of Medicine, 1470 Madison Ave, Box 1087, New York, NY 10029 (e-mail: [email protected]). Mayo Clin Proc. 2004;79:51-56
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© 2004 Mayo Foundation for Medical Education and Research
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HIV Testing in Hepatitis Patients
tioners, and 128 internal medicine residents who have their continuity practice in the clinic. A considerable proportion of the patients followed up in the clinic are minorities of low socioeconomic status. The study was performed retrospectively by identifying all patients who had positive serologic test results for HBV and/or HCV between January 1, 1999, and December 31, 1999. The primary outcome of the study was the performance of HIV testing on follow-up visits of patients with a positive HBV and/or HCV serologic test result. The secondary outcome was documentation of HIV discussion during follow-up visits. Testing for HIV was considered performed if an HIV test (HIV-1 antibody enzyme-linked immunosorbent assay [ELISA], Abbott Laboratories, Abbott Park, Ill) was ordered by the physician, if there was a history of HIV testing within 3 months of the hepatitis serologic tests, if there was documentation of the patient refusing the HIV test when offered, or if there was a record that the HIV-1 ELISA antibody test was ordered, even if test results were not available to the investigator reviewing the medical record. The outcome “HIV discussion” was defined as documentation of 3 or more HIV risk factors or documentation of 2 HIV risk factors and a record of the physician obtaining a history of prior HIV testing more than 3 months before the hepatitis serologic testing. Patients with positive hepatitis serologic test results were identified from a registry maintained by the Microbiology Department of Mount Sinai Hospital. Between January 1, 1999, and December 31, 1999, serologic test results were obtained for HBV core antibody (HBcAb) and HCV antibody (HCV Ab) (Abbott Laboratories). Medical records of these patients were reviewed to determine whether an HIV test was performed or discussed and to identify potential risk factors for absence of HIV testing when clinically indicated. A positive HIV test result was defined as a reactive HIV-1 ELISA with a positive HIV-1 Western blot result. A positive Western blot result was defined as the presence of 2 of the following bands: gp23, gp41, gp120, and/or gp160 (Abbott Laboratories). We estimated the HIV return rate as the ratio of the number of patients who returned to the clinic and received their HIV test results divided by the total number of blood samples sent to the laboratory for HIV testing. To assess whether primary care providers were more likely to test patients with HCV for HIV, we compared the proportion of patients with HCV, HBV, and HCV-HBV who were tested. Demographic information collected included age, sex, race, country of origin, and sexual orientation. Risk factors for HIV included injection drug use, condom use, number of sexual partners, and transfusions before 1987. Means ± SEMs were calculated for each variable. Univariate analysis was performed to compare the demo-
Mayo Clin Proc, January 2004, Vol 79
graphic characteristics and the presence of HIV risk factors among patients who had an HIV test performed and those who did not. These analyses were conducted using the χ2 test for proportions and the pooled t test for continuous variables. One-way analysis of variance was used to compare the mean of continuous variables among patients reactive for HCV, HBV, and HCV-HBV. P=.05 was used to determine statistical significance. All variables (demographic characteristics, HIV risk factors, and presence of an established primary care provider) were entered in a stepwise logistic regression analysis to identify a subset of variables that were significantly associated with HIV testing performance. Logistic models were built manually, with use of a forward strategy. The decision to enter or remove variables from the models was determined on the basis of the result of the likelihood ratio test. Statistical analysis was performed using SPSS statistical software, version 10.0 (SPSS Inc, Chicago, Ill). RESULTS A total of 655 and 612 serologic test results were obtained for HBcAb and HCV Ab. Of these, 178 were positive; 28 were reactive exclusively to HCV, 71 to HBcAb, and 79 to both HBcAb and HCV Ab. From an initial group of 178 patients, 37 were excluded, 14 because their medical records could not be located and 23 for not returning to the clinic for follow-up after the hepatitis serologic test results were obtained. Among the final cohort of 141 patients, 19, 57, and 65 patients had reactive serologic test results to HCV, HBV, and HCV-HBV, respectively. The group’s mean ± SEM age was 47±12 years, with 64% male and 50% Hispanic (Table 1). There were no statistically significant differences in the baseline characteristics among patients with exposure to HCV, HBV, and/or HCV-HBV, although there was a higher percentage of women in the HCV group (63%). Of the 141 patients, 48% reported being heterosexual; 46% of patients did not report their sexual orientation. Overall, HIV tests were performed in 40% (95% confidence interval [CI], 32%-49%) of the patients (Table 2). Of these, 43 blood samples were withdrawn and sent to the Mount Sinai laboratory for HIV-1 ELISA testing. Four patients (9%) tested positive for HIV, with a return rate of 74% and a mean duration of time until return of 1.8 months. Of the 141 patients, 64 (45%) had been tested for HIV at any time in the past. There was no statistically significant difference in the rate of HIV testing among patients with HCV, HBV, or HCV-HBV infection (32%, 39%, and 45%, respectively; P=.56) or discussion of HIV risks factors (32%, 39%, and 43%, respectively; P=.65), suggesting that physicians consider these 3 groups to be at similar risk of HIV infection (Table 2).
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Mayo Clin Proc, January 2004, Vol 79
HIV Testing in Hepatitis Patients
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Table 1. Comparison of Baseline Patient Characteristics According to Hepatitis Serologic Test Results*
Characteristic Age (mean ± SEM) (y) Female Ethnicity Hispanic Black Other Not available Marital status Single Married Not available Country of origin United States Puerto Rico Other MMTP No Yes Not available Sexual orientation Heterosexual Homosexual Bisexual Not available
HCV (n=19)
No. (%) of patients† HBV HCV-HBV Total (n=57) (n=65) (N=141)
47±12 12 (63)
45±13 22 (39)
49±11 17 (26)
47±12 51 (36)
12 6 1 0
26 16 6 9
32 20 9 4
70 42 16 13
(63) (32) (5) (0)
(46) (28) (10) (16)
(49) (31) (14) (6)
P value .16 .01 .31
(50) (30) (11) (9) .59
12 (63) 2 (11) 5 (26)
41 (72) 7 (12) 9 (16)
40 (62) 9 (14) 16 (24)
93 (66) 18 (13) 30 (21)
10 (53) 2 (11) 7 (36)
14 (25) 10 (18) 33 (57)
16 (25) 15 (23) 34 (52)
40 (28) 27 (19) 74 (53)
13 (68) 3 (16) 3 (16)
41 (72) 3 (5) 13 (23)
33 (51) 26 (40) 6 (9)
87 (62) 32 (23) 22 (15)
11 1 1 6
23 4 1 29
34 0 1 30
68 5 3 65
.23
.10
.25 (58) (5) (5) (32)
(40) (7) (2) (51)
(52) (0) (2) (46)
(48) (4) (2) (46)
* HBV = hepatitis B virus; HCV = hepatitis C virus; MMTP = methadone maintenance treatment program. † Unless indicated otherwise.
Factors on univariate analysis that were significantly associated with HIV testing included male sex (odds ratio [OR], 2.1; 95% CI, 1.1-4.4), enrollment in a methadone maintenance treatment program (OR, 2.3; 95% CI, 1.05.2), age younger than 50 years (OR, 3.4; 95% CI, 1.6-7.0), and having an established primary care provider (OR, 2.4; 95% CI, 1.1-5.9). Interestingly, injection drug use, a known risk factor for HIV, was not associated with a statistically significant increased rate of HIV testing in this population (OR, 1.6; 95% CI, 0.8-3.1) (Table 3). It is important to recognize that because of the limited sample size, the study may not have been powered to identify other factors potentially associated with HIV testing. Multivariate analysis revealed that age younger than 50 years (OR, 2.5; 95% CI, 1.8-3.8; P=.001), having an established primary care provider (OR, 2.3; 95% CI, 1.2-3.9; P=.01), and male sex (OR, 1.6; 95% CI, 1.1-2.2; P=.04) were independent predictors of HIV testing. DISCUSSION The results of this study show that, among adult patients with positive serologic test results for HBV and/or HCV, only 40% were tested for HIV. This reveals an important gap in the clinical management of these patients and represents a missed opportunity to reveal coinfection, decrease
secondary transmission of all the agents, and potentially improve health outcomes in these patients. The reasons for these low rates of HIV testing are probably multiple, including lack of physician knowledge, practice barriers, cultural and language barriers, lack of time, and economic factors. The importance of these factors should be explored in future studies. Our finding that older patients are less likely to be tested for HIV is cause for concern. The increasing incidence of HIV in elderly individuals is well recognized. In New York City, the percentage of people older than 40 years who are living with AIDS increased from 37% in 1992 to 42% in 1999. In contrast, the percentage of AIDS in people aged 30 to 39 years has decreased from 47% to 44% during the same period.32 If older patients are not tested, they will more likely present with HIV in the advanced stages of AIDS, having been denied the benefits of early highly active antiretroviral therapy.33-35 Also of concern is the finding that a history of injection drug use had no significant effect on the rate of HIV discussion and/or testing in our clinic. In New York City, injection drug use alone accounts for 44% of male AIDS patients and 53% of female AIDS patients; thus, the presence of this risk factor should automatically prompt physicians to order an HIV test.36
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HIV Testing in Hepatitis Patients
Mayo Clin Proc, January 2004, Vol 79
Table 2. Comparison of the Rate of HIV Test Performance and Discussion According to Hepatitis Serologic Test Results* HCV (n=19) HIV test performed† Tests obtained Tests refused Tests obtained within 3 mo Total HIV test results Reactive Nonreactive Not available Patient return rate HIV testing discussed‡
5 0
No. (%) of patients HBV HCV-HBV (n=57) (n=65)
Total (N=141)
P value
18 2
20 5
43 7
1 6 (32)
2 22 (39)
4 29 (45)
7 57 (40)
.56
1 4 0 5 6
3 14 1 15 22
0 18 2 12 28
4 36 3 32 56
.65
(20) (80) (0) (100) (32)
(17) (78) (6) (83) (39)
(0) (90) (10) (60) (43)
(9) (84) (7) (74) (40)
* HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus. † Defined as the presence of an HIV-1 enzyme-linked immunosorbent assay (ELISA) antibody test ordered by the physician on follow-up clinic visits after the hepatitis serologic tests were performed, history of HIV testing within 3 months of the hepatitis serologic tests, HIV test offered by physician with patient refusal, or HIV-1 ELISA antibody test documented in medical record as ordered with no test result available. ‡ Defined as the documentation of the presence of 3 or more HIV risk factors or 2 risk factors plus the physician obtaining a history of HIV testing more than 3 months before hepatitis serologic tests were performed.
In our study, men were statistically more likely to be tested for HIV than women. Surveillance data on the HIV epidemic in the United States show that minority heterosexual women constitute one of the fastest-growing groups of the newly infected.37 Therefore, rates of HIV testing in women must increase for recognition and treatment of this epidemic.38 Our finding that having an established primary care provider was significantly associated with increased HIV Table 3. Predictors of HIV Tests Performed on Univariate Analysis*
Predictor Male Age <50 y Single Injection drug use MMTP Established primary care provider
No. (%) of patients HIV test HIV test not performed performed (n=57)† (n=84)
OR (95% CI)
P value
42 (73) 45 (75) 39 (68)
48 (57) 35 (43) 54 (64)
2.1 (1.1-4.4) 3.4 (1.6-7.0) 1.2 (0.6-2.5)
.04 .001 .35
28 (49) 18 (32)
32 (38) 14 (17)
1.6 (0.8-3.1) 2.3 (1.0-5.2)
.27 .04
35 (64)
39 (48)
2.4 (1.1-5.9)
.05
*CI = confidence interval; HIV = human immunodeficiency virus; MMTP = methadone maintenance treatment program; OR = odds ratio. †Defined as the presence of an HIV-1 enzyme-linked immunosorbent assay (ELISA) antibody test ordered by the physician on follow-up clinic visits after the hepatitis serologic tests were performed, history of HIV testing within 3 months of the hepatitis serologic tests, HIV test offered by physician with patient refusal, or HIV-1 ELISA antibody test documented in medical record as ordered with no test result available.
testing reinforces the concept that patient outcomes are better with continuity of care.39,40 A potential explanation for this finding might be that once a relationship develops, discussions related to HIV prevention and testing will occur more comfortably and more often. Also, the intermediary physician may delay or avoid HIV testing because it involves intimate discussions. The rate of positive HIV test results in our population (9%) was comparable to the rate found in unlinked seroprevalence studies of sexually transmitted diseases in clinics in New York City.41 These data suggest that patients with serologic exposure to HBV and/or HCV are at similar risk of acquiring HIV infection as patients who participate in at-risk sexual encounters. Approximately 25% of patients who were HIV tested did not return to the clinic to obtain their test results, double the 13.3% reported in the National Health Interview Survey for 1994 and 1995.42 Mechanisms need to be developed and implemented to ensure that patients return for their test results. Our study has some methodologic limitations. It is based on a single general medicine clinic. Therefore, our findings may represent local practices and may not be highly generalizable to other settings. The information was obtained retrospectively from medical record review and probably is not as complete and accurate as when data collection is done prospectively. However, some of the data, such as the results of the HBcAb and/or HCV Ab serologic testing and the HIV-1 ELISA and HIV-1 Western blots, were not subject to these problems. Because of in-
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Mayo Clin Proc, January 2004, Vol 79
complete documentation in the medical record or low rates of patient-physician discussion of HIV risk behaviors, there was a paucity of data available on some important HIV risk factors, with more than 80% of data missing regarding condom use, history of transfusions before 1987, history of prostitution, and history of sex with an HIVpositive partner. This lack of information limited our ability to control for these variables in the multivariate analysis. Finally, the sample size may have limited our ability to identify other important predictors of HIV testing. Our data suggest a high rate of HIV testing if there was a patient-physician discussion of HIV risk factors and history of HIV testing. Only 7 (12%) of 57 patients refused HIV testing when discussion occurred, suggesting that if the physician initiates the discussion, HIV testing almost always occurs. These findings are similar to the results of a study conducted in Massachusetts that examined factors associated with HIV testing in sexually active adolescents.43 In this study, one of the strongest associations with HIV testing was a physician-patient discussion on testing, with 85% of the tests performed secondary to discussion initiated by physicians. CONCLUSIONS This study showed a high number of missed opportunities for HIV testing in a high-risk population followed up at a general internal medicine clinic. Further research needs to be conducted to assess factors that may contribute to the poor rate of HIV testing in these high-risk patients. Education of general internal medicine physicians about the risks of coinfection may increase rates of HIV testing in at-risk patients. Streamlining pathways to diagnose coinfection could then allow for earlier therapeutic interventions, improved patient outcomes, and secondary prevention of all 3 viruses within the local and global communities.
HIV Testing in Hepatitis Patients
7.
8. 9. 10.
11.
12.
13.
14.
15. 16. 17.
18.
19. 20.
REFERENCES 1.
2. 3.
4.
5. 6.
Coleman PJ, McQuillan GM, Moyer LA, Lambert SB, Margolis HS. Incidence of hepatitis B virus infection in the United States, 1976-1994: estimates from the National Health and Nutrition Examination Surveys. J Infect Dis. 1998;178:954-959. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCVrelated chronic disease. MMWR Recomm Rep. 1998;47(RR-19):1-39. Centers for Disease Control and Prevention. HIV/AIDS surveillance report: U.S. HIV and AIDS cases reported through December 2000: year-ed, Vol 12, No. 2. Available at: www.cdc.gov/hiv/stats/ hasr1202.htm. Accessibility verified November 14, 2003. Garfein RS, Vlahov D, Galai N, Doherty MC, Nelson KE. Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human Tlymphotropic viruses. Am J Public Health. 1996;86:655-661. Centers for Disease Control and Prevention. 1998 Guidelines for treatment of sexually transmitted diseases. MMWR Recomm Rep. 1998;47(RR-1):1-111. Centers for Disease Control and Prevention. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United
21.
22.
23.
24.
25.
26.
55
States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991;40(RR-13):1-25. Eyster ME, Alter HJ, Aledort LM, Quan S, Hatzakis A, Goedert JJ. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann Intern Med. 1991;115: 764-768. Makris M, Preston FE, Rosendaal FR, Underwood JC, Rice KM, Triger DR. The natural history of chronic hepatitis C in haemophiliacs. Br J Haematol. 1996;94:746-752. Tabet SR, Palmer D, Wiese WH, Voorhees RE, Pathak DR. Seroprevalence of HIV-1 and hepatitis B and C in prostitutes in Albuquerque, New Mexico. Am J Public Health. 1992;82:1151-1154. Centers for Disease Control and Prevention. Prevalence of hepatitis C virus infection among clients of HIV counseling and testing sites—Connecticut, 1999. MMWR Morb Mortal Wkly Rep. 2001; 50:577-581. Sherman KE, Rouster SD, Chung RT, Rejicic N. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002;34:831-837. Long J, Allwright S, Barry J, et al. Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in entrants to Irish prisons: a national cross sectional survey. BMJ. 2001;323:12091213. Gunn RA, Murray PJ, Ackers ML, Hardison WG, Margolis HS. Screening for chronic hepatitis B and C virus infections in an urban sexually transmitted disease clinic: rationale for integrating services. Sex Transm Dis. 2001;28:166-170. Montecalvo MA, Lee MS, DePalma H, et al. Seroprevalence of human immunodeficiency virus-1, hepatitis B virus, and hepatitis C virus in patients having major surgery. Infect Control Hosp Epidemiol. 1995;16:627-632. Weinstock DM, Merrick S, Malak SA, Jacobs J, Sepkowitz KA. Hepatitis C in an urban population infected with the human immunodeficiency virus. AIDS. 1999;13:2593-2595. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. McLean, Va: International Medical Publishing; 1996. Healthy People 2010: HIV. Available at: www.healthypeople.gov/ document/html/volume1/13hiv.htm. Accessibility verified November 14, 2003. Weinstock H, Dale M, Linley L, Gwinn M. Unrecognized HIV infection among patients attending sexually transmitted disease clinics. Am J Public Health. 2002;92:280-283. Vergis EN, Mellors JW. Natural history of HIV-1 infection. Infect Dis Clin North Am. 2000;14:809-825. Chung RT, Kim AY, Polsky B. HIV/Hepatitis B and C co-infection: pathogenic interactions, natural history and therapy. Antivir Chem Chemother. 2001;12(suppl 1):73-91. Graham CS, Baden LR, Yu E, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33:562-569. Bica I, McGovern B, Dhar R, et al. Increasing mortality due to endstage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis. 2001;32:492-497. Zylberberg H, Pialoux G, Carnot F, Landau A, Brechot C, Pol S. Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy. Clin Infect Dis. 1998;27:1255-1258. Poles MA, Dieterich DT. Hepatitis C virus/human immunodeficiency virus coinfection: clinical management issues. Clin Infect Dis. 2000;31:154-161. Landau A, Batisse D, Van Huyen JP, et al. Efficacy and safety of combination therapy with interferon-α2b and ribavirin for chronic hepatitis C in HIV-infected patients. AIDS. 2000;14:839-844. Nasti G, DiGennaro G, Tavio M, et al. Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alfa-2b and tribavirin. AIDS. 2001;15:1783-1787.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
56
27.
28.
29. 30.
31.
32.
33. 34. 35.
HIV Testing in Hepatitis Patients
Soriano V, Garcia-Samaniego J, Bravo R, et al, Hepatitis-HIV Spanish Study Group. Interferon alfa for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Clin Infect Dis. 1996;23:585-591. Soriano V, Garcia-Samaniego J, Bravo R, et al, HIV-Hepatitis Spanish Study Group. Efficacy and safety of alfa-interferon treatment for chronic hepatitis C in HIV-infected patients. J Infect. 1995;31:9-13. Soriano V, Rodriguez-Rosado R, Garcia-Samaniego J. Management of chronic hepatitis C in HIV-infected patients [editorial]. AIDS. 1999;13:539-546. Sulkowski M. The treatment of chronic HCV in HIV-infected persons. In: Programs and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; San Francisco, Calif; January 30-February 4, 2000. Abstract S11. Dieterich DT, Purow JM, Rajapaksa R. Activity of combination therapy with interferon alfa-2ab plus ribavirin in chronic hepatitis C patients co-infected with HIV. Semin Liver Dis. 1999;19(suppl 1):87-94. New York City Department of Health, Office of AIDS Surveillance. Estimates of Persons Living with AIDS in New York City, 1999 Edition. New York, NY: New York City Department of Health; March 2000. Carpenter CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000;283:381-390. Knobel H, Guelar A, Valldecillo G, et al. Response to highly active antiretroviral therapy in HIV-infected patients age 60 years or older after 24 months follow-up. AIDS. 2001;15:1591-1593. Jacobson LP, Li R, Phair J, et al. Evaluation of the effectiveness of highly active antiretroviral therapy in persons with human immu-
Mayo Clin Proc, January 2004, Vol 79
36.
37.
38.
39. 40.
41. 42.
43.
nodeficiency virus using biomarker-based equivalence of disease progression. Am J Epidemiol. 2002;155:760-770. New York City Department of Health, Office of AIDS Surveillance. AIDS in the Boroughs and Neighborhoods of New York City. Vol 3. New York, NY: New York City Department of Health; 1999. Centers for Disease Control and Prevention. HIV and AIDS— United States, 1981-2000 [published correction appears in MMWR Morb Mortal Wkly Rep. 2001;50:1066]. MMWR Morb Mortal Wkly Rep. 2001;50:430-434. Gange SJ, Barron Y, Greenblatt RM, et al, Women’s Interagency HIV Study Collaborative Study Group. Effectiveness of highly active antiretroviral therapy among HIV-1 infected women. J Epidemiol Community Health. 2002;56:153-159. O’Malley AS, Forrest CB. Beyond the examination room: primary care performance and the patient-physician relationship for lowincome women. J Gen Intern Med. 2002;17:66-74. Mainous AG III, Baker R, Love MM, Gray DP, Gill JM. Continuity of care and trust in one’s physician: evidence from primary care in the United States and the United Kingdom. Fam Med. 2001;33:2227. HIV Seroprevalence in NYC STD Clinics, unlinked serosurveys, 1990-1998. HIV Seroprevalence Update, 1998. New York City Department of Health, Office of AIDS Research/HIV Serosurveys. Tao G, Branson BM, Kassler WJ, Cohen RA. Rates of receiving HIV test results: data from the U.S. National Health Interview Survey for 1994 and 1995. J Acquir Immune Defic Syndr. 1999; 22:395-400. Samet JH, Winter MR, Grant L, Hingson R. Factors associated with HIV testing among sexually active adolescents: a Massachusetts survey. Pediatrics. 1997;100(3, pt 1):371-377.
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51
Original Article
Prevalence of Human Immunodeficiency Virus Testing in Patients With Hepatitis B and C Infection ALYSA KRAIN, MD, MSC; JUAN P. WISNIVESKY, MD; ELIZABETH GARLAND, MD, MS; AND THOMAS MCGINN, MD, MPH
• Objectives: To determine the proportion of patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) who are adequately assessed for human immunodeficiency virus (HIV) and to identify variables associated with absence of HIV testing. • Patients and Methods: We retrospectively reviewed the medical records of patients who had positive serologic test results for reactive HBV and/or HCV between January 1999 and December 1999 and were followed up at a general internal medicine clinic in East Harlem, NY. Data were collected on patient demographics, HIV risk factors, and other variables that might influence the physician’s decision to test the patient for HIV. Primary outcomes were HIV tests performed and documented discussions of at-risk HIV behavior. • Results: The HIV tests were performed in 40% (95% confidence interval [CI], 32%-49%) of the 141 patients with reactive HBV and/or HCV serologic test results. Predictors of HIV testing on multivariate logistic regression
were age younger than 50 years (odds ratio [OR], 2.5; 95% CI, 1.8-3.8), male sex (OR, 1.6; 95% CI, 1.1-2.2), and having an established primary care provider (OR, 2.3; 95% CI, 1.2-3.9). Injection drug use was not significantly associated with HIV testing. • Conclusions: Although HBV and HCV have clear epidemiological links with HIV, this study shows that a high percentage of these patients are not being tested. Although some of the factors associated with lack of testing were identified, further studies on the barriers to HIV testing are needed to reveal potential approaches to increase rates of HIV testing in this high-risk population. Mayo Clin Proc. 2004;79:51-56 AIDS = acquired immunodeficiency syndrome; CI = confidence interval; ELISA = enzyme-linked immunosorbent assay; HBcAb = hepatitis B core antibody; HBV = hepatitis B virus; HCV = hepatitis C virus; HCV Ab = hepatitis C virus antibody; HIV = human immunodeficiency virus; OR = odds ratio
H
epatitis B virus (HBV) and hepatitis C virus (HCV) are common, with 12.5 million and 3.9 million Americans having been exposed to HBV and HCV, respectively.1,2 Although human immunodeficiency virus (HIV) is less prevalent, the epidemiological features of HBV, HCV, and HIV make the incidence of coinfection likely.3-10 The prevalence of HBV and HCV infection has been well described in HIV cohorts; however, the epidemiological features are not well known.11-15 Despite multiple guidelines that indicate the need for HIV testing of patients who practice at-risk behaviors, missed opportunities exist.16 Estimates show that in 1998, approximately 250,000 people in the United States were unaware of their HIV diagnosis.17,18 This problem is espe-
cially serious among patients with HBV and/or HCV because delay in diagnosis may result in patients presenting not only with an advanced stage of acquired immunodeficiency syndrome (AIDS) but also with rapidly progressed viral hepatitis.19-24 Ultimately, these missed diagnoses may lead to worse patient outcomes and/or more complicated therapeutic decisions. Early diagnosis is even more important in light of recent data that show promising therapeutic interventions for HCV-HIV coinfected patients in the early stages of HIV disease (CD4 cell count, >500 × 106/L).25-31 The prevalence and predictors of HIV testing rates among patients with serologic exposure to viral hepatitis have not been studied previously. This information is important for developing strategies to improve the outcomes of these high-risk populations. The objective of this study was to determine the proportion of patients with HBV and HCV exposure who were adequately assessed for the presence of HIV and to identify variables associated with the absence of HIV testing when clinically indicated.
From the Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, NY (A.K.); and Division of General Internal Medicine (J.P.W., T.M.) and Department of Community and Preventive Medicine (E.G.), Mount Sinai Medical Center, New York, NY. Presented as a poster at the 24th Annual National Meeting of the Society of General Internal Medicine, San Diego, Calif, May 3-5, 2000.
PATIENTS AND METHODS The study was conducted at a general internal medicine clinic in East Harlem, NY, which serves approximately 14,000 patients per year. The ambulatory center is composed of 30 full-time attending physicians, 4 nurse practi-
Individual reprints of this article are not available. Address correspondence to Juan P. Wisnivesky, MD, Division of General Internal Medicine, Mount Sinai School of Medicine, 1470 Madison Ave, Box 1087, New York, NY 10029 (e-mail: [email protected]). Mayo Clin Proc. 2004;79:51-56
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© 2004 Mayo Foundation for Medical Education and Research
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HIV Testing in Hepatitis Patients
tioners, and 128 internal medicine residents who have their continuity practice in the clinic. A considerable proportion of the patients followed up in the clinic are minorities of low socioeconomic status. The study was performed retrospectively by identifying all patients who had positive serologic test results for HBV and/or HCV between January 1, 1999, and December 31, 1999. The primary outcome of the study was the performance of HIV testing on follow-up visits of patients with a positive HBV and/or HCV serologic test result. The secondary outcome was documentation of HIV discussion during follow-up visits. Testing for HIV was considered performed if an HIV test (HIV-1 antibody enzyme-linked immunosorbent assay [ELISA], Abbott Laboratories, Abbott Park, Ill) was ordered by the physician, if there was a history of HIV testing within 3 months of the hepatitis serologic tests, if there was documentation of the patient refusing the HIV test when offered, or if there was a record that the HIV-1 ELISA antibody test was ordered, even if test results were not available to the investigator reviewing the medical record. The outcome “HIV discussion” was defined as documentation of 3 or more HIV risk factors or documentation of 2 HIV risk factors and a record of the physician obtaining a history of prior HIV testing more than 3 months before the hepatitis serologic testing. Patients with positive hepatitis serologic test results were identified from a registry maintained by the Microbiology Department of Mount Sinai Hospital. Between January 1, 1999, and December 31, 1999, serologic test results were obtained for HBV core antibody (HBcAb) and HCV antibody (HCV Ab) (Abbott Laboratories). Medical records of these patients were reviewed to determine whether an HIV test was performed or discussed and to identify potential risk factors for absence of HIV testing when clinically indicated. A positive HIV test result was defined as a reactive HIV-1 ELISA with a positive HIV-1 Western blot result. A positive Western blot result was defined as the presence of 2 of the following bands: gp23, gp41, gp120, and/or gp160 (Abbott Laboratories). We estimated the HIV return rate as the ratio of the number of patients who returned to the clinic and received their HIV test results divided by the total number of blood samples sent to the laboratory for HIV testing. To assess whether primary care providers were more likely to test patients with HCV for HIV, we compared the proportion of patients with HCV, HBV, and HCV-HBV who were tested. Demographic information collected included age, sex, race, country of origin, and sexual orientation. Risk factors for HIV included injection drug use, condom use, number of sexual partners, and transfusions before 1987. Means ± SEMs were calculated for each variable. Univariate analysis was performed to compare the demo-
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graphic characteristics and the presence of HIV risk factors among patients who had an HIV test performed and those who did not. These analyses were conducted using the χ2 test for proportions and the pooled t test for continuous variables. One-way analysis of variance was used to compare the mean of continuous variables among patients reactive for HCV, HBV, and HCV-HBV. P=.05 was used to determine statistical significance. All variables (demographic characteristics, HIV risk factors, and presence of an established primary care provider) were entered in a stepwise logistic regression analysis to identify a subset of variables that were significantly associated with HIV testing performance. Logistic models were built manually, with use of a forward strategy. The decision to enter or remove variables from the models was determined on the basis of the result of the likelihood ratio test. Statistical analysis was performed using SPSS statistical software, version 10.0 (SPSS Inc, Chicago, Ill). RESULTS A total of 655 and 612 serologic test results were obtained for HBcAb and HCV Ab. Of these, 178 were positive; 28 were reactive exclusively to HCV, 71 to HBcAb, and 79 to both HBcAb and HCV Ab. From an initial group of 178 patients, 37 were excluded, 14 because their medical records could not be located and 23 for not returning to the clinic for follow-up after the hepatitis serologic test results were obtained. Among the final cohort of 141 patients, 19, 57, and 65 patients had reactive serologic test results to HCV, HBV, and HCV-HBV, respectively. The group’s mean ± SEM age was 47±12 years, with 64% male and 50% Hispanic (Table 1). There were no statistically significant differences in the baseline characteristics among patients with exposure to HCV, HBV, and/or HCV-HBV, although there was a higher percentage of women in the HCV group (63%). Of the 141 patients, 48% reported being heterosexual; 46% of patients did not report their sexual orientation. Overall, HIV tests were performed in 40% (95% confidence interval [CI], 32%-49%) of the patients (Table 2). Of these, 43 blood samples were withdrawn and sent to the Mount Sinai laboratory for HIV-1 ELISA testing. Four patients (9%) tested positive for HIV, with a return rate of 74% and a mean duration of time until return of 1.8 months. Of the 141 patients, 64 (45%) had been tested for HIV at any time in the past. There was no statistically significant difference in the rate of HIV testing among patients with HCV, HBV, or HCV-HBV infection (32%, 39%, and 45%, respectively; P=.56) or discussion of HIV risks factors (32%, 39%, and 43%, respectively; P=.65), suggesting that physicians consider these 3 groups to be at similar risk of HIV infection (Table 2).
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HIV Testing in Hepatitis Patients
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Table 1. Comparison of Baseline Patient Characteristics According to Hepatitis Serologic Test Results*
Characteristic Age (mean ± SEM) (y) Female Ethnicity Hispanic Black Other Not available Marital status Single Married Not available Country of origin United States Puerto Rico Other MMTP No Yes Not available Sexual orientation Heterosexual Homosexual Bisexual Not available
HCV (n=19)
No. (%) of patients† HBV HCV-HBV Total (n=57) (n=65) (N=141)
47±12 12 (63)
45±13 22 (39)
49±11 17 (26)
47±12 51 (36)
12 6 1 0
26 16 6 9
32 20 9 4
70 42 16 13
(63) (32) (5) (0)
(46) (28) (10) (16)
(49) (31) (14) (6)
P value .16 .01 .31
(50) (30) (11) (9) .59
12 (63) 2 (11) 5 (26)
41 (72) 7 (12) 9 (16)
40 (62) 9 (14) 16 (24)
93 (66) 18 (13) 30 (21)
10 (53) 2 (11) 7 (36)
14 (25) 10 (18) 33 (57)
16 (25) 15 (23) 34 (52)
40 (28) 27 (19) 74 (53)
13 (68) 3 (16) 3 (16)
41 (72) 3 (5) 13 (23)
33 (51) 26 (40) 6 (9)
87 (62) 32 (23) 22 (15)
11 1 1 6
23 4 1 29
34 0 1 30
68 5 3 65
.23
.10
.25 (58) (5) (5) (32)
(40) (7) (2) (51)
(52) (0) (2) (46)
(48) (4) (2) (46)
* HBV = hepatitis B virus; HCV = hepatitis C virus; MMTP = methadone maintenance treatment program. † Unless indicated otherwise.
Factors on univariate analysis that were significantly associated with HIV testing included male sex (odds ratio [OR], 2.1; 95% CI, 1.1-4.4), enrollment in a methadone maintenance treatment program (OR, 2.3; 95% CI, 1.05.2), age younger than 50 years (OR, 3.4; 95% CI, 1.6-7.0), and having an established primary care provider (OR, 2.4; 95% CI, 1.1-5.9). Interestingly, injection drug use, a known risk factor for HIV, was not associated with a statistically significant increased rate of HIV testing in this population (OR, 1.6; 95% CI, 0.8-3.1) (Table 3). It is important to recognize that because of the limited sample size, the study may not have been powered to identify other factors potentially associated with HIV testing. Multivariate analysis revealed that age younger than 50 years (OR, 2.5; 95% CI, 1.8-3.8; P=.001), having an established primary care provider (OR, 2.3; 95% CI, 1.2-3.9; P=.01), and male sex (OR, 1.6; 95% CI, 1.1-2.2; P=.04) were independent predictors of HIV testing. DISCUSSION The results of this study show that, among adult patients with positive serologic test results for HBV and/or HCV, only 40% were tested for HIV. This reveals an important gap in the clinical management of these patients and represents a missed opportunity to reveal coinfection, decrease
secondary transmission of all the agents, and potentially improve health outcomes in these patients. The reasons for these low rates of HIV testing are probably multiple, including lack of physician knowledge, practice barriers, cultural and language barriers, lack of time, and economic factors. The importance of these factors should be explored in future studies. Our finding that older patients are less likely to be tested for HIV is cause for concern. The increasing incidence of HIV in elderly individuals is well recognized. In New York City, the percentage of people older than 40 years who are living with AIDS increased from 37% in 1992 to 42% in 1999. In contrast, the percentage of AIDS in people aged 30 to 39 years has decreased from 47% to 44% during the same period.32 If older patients are not tested, they will more likely present with HIV in the advanced stages of AIDS, having been denied the benefits of early highly active antiretroviral therapy.33-35 Also of concern is the finding that a history of injection drug use had no significant effect on the rate of HIV discussion and/or testing in our clinic. In New York City, injection drug use alone accounts for 44% of male AIDS patients and 53% of female AIDS patients; thus, the presence of this risk factor should automatically prompt physicians to order an HIV test.36
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Table 2. Comparison of the Rate of HIV Test Performance and Discussion According to Hepatitis Serologic Test Results* HCV (n=19) HIV test performed† Tests obtained Tests refused Tests obtained within 3 mo Total HIV test results Reactive Nonreactive Not available Patient return rate HIV testing discussed‡
5 0
No. (%) of patients HBV HCV-HBV (n=57) (n=65)
Total (N=141)
P value
18 2
20 5
43 7
1 6 (32)
2 22 (39)
4 29 (45)
7 57 (40)
.56
1 4 0 5 6
3 14 1 15 22
0 18 2 12 28
4 36 3 32 56
.65
(20) (80) (0) (100) (32)
(17) (78) (6) (83) (39)
(0) (90) (10) (60) (43)
(9) (84) (7) (74) (40)
* HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus. † Defined as the presence of an HIV-1 enzyme-linked immunosorbent assay (ELISA) antibody test ordered by the physician on follow-up clinic visits after the hepatitis serologic tests were performed, history of HIV testing within 3 months of the hepatitis serologic tests, HIV test offered by physician with patient refusal, or HIV-1 ELISA antibody test documented in medical record as ordered with no test result available. ‡ Defined as the documentation of the presence of 3 or more HIV risk factors or 2 risk factors plus the physician obtaining a history of HIV testing more than 3 months before hepatitis serologic tests were performed.
In our study, men were statistically more likely to be tested for HIV than women. Surveillance data on the HIV epidemic in the United States show that minority heterosexual women constitute one of the fastest-growing groups of the newly infected.37 Therefore, rates of HIV testing in women must increase for recognition and treatment of this epidemic.38 Our finding that having an established primary care provider was significantly associated with increased HIV Table 3. Predictors of HIV Tests Performed on Univariate Analysis*
Predictor Male Age <50 y Single Injection drug use MMTP Established primary care provider
No. (%) of patients HIV test HIV test not performed performed (n=57)† (n=84)
OR (95% CI)
P value
42 (73) 45 (75) 39 (68)
48 (57) 35 (43) 54 (64)
2.1 (1.1-4.4) 3.4 (1.6-7.0) 1.2 (0.6-2.5)
.04 .001 .35
28 (49) 18 (32)
32 (38) 14 (17)
1.6 (0.8-3.1) 2.3 (1.0-5.2)
.27 .04
35 (64)
39 (48)
2.4 (1.1-5.9)
.05
*CI = confidence interval; HIV = human immunodeficiency virus; MMTP = methadone maintenance treatment program; OR = odds ratio. †Defined as the presence of an HIV-1 enzyme-linked immunosorbent assay (ELISA) antibody test ordered by the physician on follow-up clinic visits after the hepatitis serologic tests were performed, history of HIV testing within 3 months of the hepatitis serologic tests, HIV test offered by physician with patient refusal, or HIV-1 ELISA antibody test documented in medical record as ordered with no test result available.
testing reinforces the concept that patient outcomes are better with continuity of care.39,40 A potential explanation for this finding might be that once a relationship develops, discussions related to HIV prevention and testing will occur more comfortably and more often. Also, the intermediary physician may delay or avoid HIV testing because it involves intimate discussions. The rate of positive HIV test results in our population (9%) was comparable to the rate found in unlinked seroprevalence studies of sexually transmitted diseases in clinics in New York City.41 These data suggest that patients with serologic exposure to HBV and/or HCV are at similar risk of acquiring HIV infection as patients who participate in at-risk sexual encounters. Approximately 25% of patients who were HIV tested did not return to the clinic to obtain their test results, double the 13.3% reported in the National Health Interview Survey for 1994 and 1995.42 Mechanisms need to be developed and implemented to ensure that patients return for their test results. Our study has some methodologic limitations. It is based on a single general medicine clinic. Therefore, our findings may represent local practices and may not be highly generalizable to other settings. The information was obtained retrospectively from medical record review and probably is not as complete and accurate as when data collection is done prospectively. However, some of the data, such as the results of the HBcAb and/or HCV Ab serologic testing and the HIV-1 ELISA and HIV-1 Western blots, were not subject to these problems. Because of in-
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Mayo Clin Proc, January 2004, Vol 79
complete documentation in the medical record or low rates of patient-physician discussion of HIV risk behaviors, there was a paucity of data available on some important HIV risk factors, with more than 80% of data missing regarding condom use, history of transfusions before 1987, history of prostitution, and history of sex with an HIVpositive partner. This lack of information limited our ability to control for these variables in the multivariate analysis. Finally, the sample size may have limited our ability to identify other important predictors of HIV testing. Our data suggest a high rate of HIV testing if there was a patient-physician discussion of HIV risk factors and history of HIV testing. Only 7 (12%) of 57 patients refused HIV testing when discussion occurred, suggesting that if the physician initiates the discussion, HIV testing almost always occurs. These findings are similar to the results of a study conducted in Massachusetts that examined factors associated with HIV testing in sexually active adolescents.43 In this study, one of the strongest associations with HIV testing was a physician-patient discussion on testing, with 85% of the tests performed secondary to discussion initiated by physicians. CONCLUSIONS This study showed a high number of missed opportunities for HIV testing in a high-risk population followed up at a general internal medicine clinic. Further research needs to be conducted to assess factors that may contribute to the poor rate of HIV testing in these high-risk patients. Education of general internal medicine physicians about the risks of coinfection may increase rates of HIV testing in at-risk patients. Streamlining pathways to diagnose coinfection could then allow for earlier therapeutic interventions, improved patient outcomes, and secondary prevention of all 3 viruses within the local and global communities.
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7.
8. 9. 10.
11.
12.
13.
14.
15. 16. 17.
18.
19. 20.
REFERENCES 1.
2. 3.
4.
5. 6.
Coleman PJ, McQuillan GM, Moyer LA, Lambert SB, Margolis HS. Incidence of hepatitis B virus infection in the United States, 1976-1994: estimates from the National Health and Nutrition Examination Surveys. J Infect Dis. 1998;178:954-959. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCVrelated chronic disease. MMWR Recomm Rep. 1998;47(RR-19):1-39. Centers for Disease Control and Prevention. HIV/AIDS surveillance report: U.S. HIV and AIDS cases reported through December 2000: year-ed, Vol 12, No. 2. Available at: www.cdc.gov/hiv/stats/ hasr1202.htm. Accessibility verified November 14, 2003. Garfein RS, Vlahov D, Galai N, Doherty MC, Nelson KE. Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human Tlymphotropic viruses. Am J Public Health. 1996;86:655-661. Centers for Disease Control and Prevention. 1998 Guidelines for treatment of sexually transmitted diseases. MMWR Recomm Rep. 1998;47(RR-1):1-111. Centers for Disease Control and Prevention. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United
21.
22.
23.
24.
25.
26.
55
States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991;40(RR-13):1-25. Eyster ME, Alter HJ, Aledort LM, Quan S, Hatzakis A, Goedert JJ. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann Intern Med. 1991;115: 764-768. Makris M, Preston FE, Rosendaal FR, Underwood JC, Rice KM, Triger DR. The natural history of chronic hepatitis C in haemophiliacs. Br J Haematol. 1996;94:746-752. Tabet SR, Palmer D, Wiese WH, Voorhees RE, Pathak DR. Seroprevalence of HIV-1 and hepatitis B and C in prostitutes in Albuquerque, New Mexico. Am J Public Health. 1992;82:1151-1154. Centers for Disease Control and Prevention. Prevalence of hepatitis C virus infection among clients of HIV counseling and testing sites—Connecticut, 1999. MMWR Morb Mortal Wkly Rep. 2001; 50:577-581. Sherman KE, Rouster SD, Chung RT, Rejicic N. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002;34:831-837. Long J, Allwright S, Barry J, et al. Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in entrants to Irish prisons: a national cross sectional survey. BMJ. 2001;323:12091213. Gunn RA, Murray PJ, Ackers ML, Hardison WG, Margolis HS. Screening for chronic hepatitis B and C virus infections in an urban sexually transmitted disease clinic: rationale for integrating services. Sex Transm Dis. 2001;28:166-170. Montecalvo MA, Lee MS, DePalma H, et al. Seroprevalence of human immunodeficiency virus-1, hepatitis B virus, and hepatitis C virus in patients having major surgery. Infect Control Hosp Epidemiol. 1995;16:627-632. Weinstock DM, Merrick S, Malak SA, Jacobs J, Sepkowitz KA. Hepatitis C in an urban population infected with the human immunodeficiency virus. AIDS. 1999;13:2593-2595. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. McLean, Va: International Medical Publishing; 1996. Healthy People 2010: HIV. Available at: www.healthypeople.gov/ document/html/volume1/13hiv.htm. Accessibility verified November 14, 2003. Weinstock H, Dale M, Linley L, Gwinn M. Unrecognized HIV infection among patients attending sexually transmitted disease clinics. Am J Public Health. 2002;92:280-283. Vergis EN, Mellors JW. Natural history of HIV-1 infection. Infect Dis Clin North Am. 2000;14:809-825. Chung RT, Kim AY, Polsky B. HIV/Hepatitis B and C co-infection: pathogenic interactions, natural history and therapy. Antivir Chem Chemother. 2001;12(suppl 1):73-91. Graham CS, Baden LR, Yu E, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33:562-569. Bica I, McGovern B, Dhar R, et al. Increasing mortality due to endstage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis. 2001;32:492-497. Zylberberg H, Pialoux G, Carnot F, Landau A, Brechot C, Pol S. Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy. Clin Infect Dis. 1998;27:1255-1258. Poles MA, Dieterich DT. Hepatitis C virus/human immunodeficiency virus coinfection: clinical management issues. Clin Infect Dis. 2000;31:154-161. Landau A, Batisse D, Van Huyen JP, et al. Efficacy and safety of combination therapy with interferon-α2b and ribavirin for chronic hepatitis C in HIV-infected patients. AIDS. 2000;14:839-844. Nasti G, DiGennaro G, Tavio M, et al. Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alfa-2b and tribavirin. AIDS. 2001;15:1783-1787.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
56
27.
28.
29. 30.
31.
32.
33. 34. 35.
HIV Testing in Hepatitis Patients
Soriano V, Garcia-Samaniego J, Bravo R, et al, Hepatitis-HIV Spanish Study Group. Interferon alfa for the treatment of chronic hepatitis C in patients infected with human immunodeficiency virus. Clin Infect Dis. 1996;23:585-591. Soriano V, Garcia-Samaniego J, Bravo R, et al, HIV-Hepatitis Spanish Study Group. Efficacy and safety of alfa-interferon treatment for chronic hepatitis C in HIV-infected patients. J Infect. 1995;31:9-13. Soriano V, Rodriguez-Rosado R, Garcia-Samaniego J. Management of chronic hepatitis C in HIV-infected patients [editorial]. AIDS. 1999;13:539-546. Sulkowski M. The treatment of chronic HCV in HIV-infected persons. In: Programs and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; San Francisco, Calif; January 30-February 4, 2000. Abstract S11. Dieterich DT, Purow JM, Rajapaksa R. Activity of combination therapy with interferon alfa-2ab plus ribavirin in chronic hepatitis C patients co-infected with HIV. Semin Liver Dis. 1999;19(suppl 1):87-94. New York City Department of Health, Office of AIDS Surveillance. Estimates of Persons Living with AIDS in New York City, 1999 Edition. New York, NY: New York City Department of Health; March 2000. Carpenter CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000;283:381-390. Knobel H, Guelar A, Valldecillo G, et al. Response to highly active antiretroviral therapy in HIV-infected patients age 60 years or older after 24 months follow-up. AIDS. 2001;15:1591-1593. Jacobson LP, Li R, Phair J, et al. Evaluation of the effectiveness of highly active antiretroviral therapy in persons with human immu-
Mayo Clin Proc, January 2004, Vol 79
36.
37.
38.
39. 40.
41. 42.
43.
nodeficiency virus using biomarker-based equivalence of disease progression. Am J Epidemiol. 2002;155:760-770. New York City Department of Health, Office of AIDS Surveillance. AIDS in the Boroughs and Neighborhoods of New York City. Vol 3. New York, NY: New York City Department of Health; 1999. Centers for Disease Control and Prevention. HIV and AIDS— United States, 1981-2000 [published correction appears in MMWR Morb Mortal Wkly Rep. 2001;50:1066]. MMWR Morb Mortal Wkly Rep. 2001;50:430-434. Gange SJ, Barron Y, Greenblatt RM, et al, Women’s Interagency HIV Study Collaborative Study Group. Effectiveness of highly active antiretroviral therapy among HIV-1 infected women. J Epidemiol Community Health. 2002;56:153-159. O’Malley AS, Forrest CB. Beyond the examination room: primary care performance and the patient-physician relationship for lowincome women. J Gen Intern Med. 2002;17:66-74. Mainous AG III, Baker R, Love MM, Gray DP, Gill JM. Continuity of care and trust in one’s physician: evidence from primary care in the United States and the United Kingdom. Fam Med. 2001;33:2227. HIV Seroprevalence in NYC STD Clinics, unlinked serosurveys, 1990-1998. HIV Seroprevalence Update, 1998. New York City Department of Health, Office of AIDS Research/HIV Serosurveys. Tao G, Branson BM, Kassler WJ, Cohen RA. Rates of receiving HIV test results: data from the U.S. National Health Interview Survey for 1994 and 1995. J Acquir Immune Defic Syndr. 1999; 22:395-400. Samet JH, Winter MR, Grant L, Hingson R. Factors associated with HIV testing among sexually active adolescents: a Massachusetts survey. Pediatrics. 1997;100(3, pt 1):371-377.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.