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Brief Report |

Barriers to Use of Free Antiretroviral Therapy in Injection Drug Users FREE

Steffanie A. Strathdee, PhD; Anita Palepu, MD, MPH; Peter G. A. Cornelisse, MSc; Benita Yip, BSc (Pharm); Michael V. O'Shaughnessy, OBC, PhD; Julio S. G. Montaner, MD, FRCPC; Martin T. Schechter, OBC, MD, PhD; Robert S. Hogg, MA, PhD
[+] Author Affiliations

From the British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital (Drs Strathdee, Palepu, O'Shaughnessy, Montaner, Schechter, and Hogg, Mr Cornelisse, and Ms Yip), Departments of Health Care and Epidemiology (Drs Strathdee, Schechter, and Hogg) and Medicine (Drs Palepu and Montaner), Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Dr Strathdee is now at the Johns Hopkins University School of Hygiene and Public Health, Baltimore, Md).


JAMA. 1998;280(6):547-549. doi:10.1001/jama.280.6.547.
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Published online

Context.— In British Columbia, human immunodeficiency virus (HIV)–infected persons eligible for antiretroviral therapy may receive it free but the extent to which HIV-infected injection drug users access it is unknown.

Objective.— To identify patient and physician characteristics associated with antiretroviral therapy utilization in HIV-infected injection drug users.

Design.— Prospective cohort study with record linkage between survey data and data from a provincial HIV/AIDS (acquired immunodeficiency syndrome) drug treatment program.

Setting.— British Columbia, where antiretroviral therapies are offered free to all persons with HIV infection with CD4 cell counts less than 0.50×109/L (500/µL) and/or HIV-1 RNA levels higher than 5000 copies/mL.

Subjects.— A total of 177 HIV-infected injection drug users eligible for antiretroviral therapy, recruited through the prospective cohort study since May 1996.

Main Outcome Measures.— Patient use of antiretroviral drugs through the provincial drug treatment program and physician experience treating HIV infection.

Results.— After a median of 11 months after first eligibility, only 71 (40%) of 177 patients had received any antiretroviral drugs, primarily double combinations (47/71 [66%]). Both patient and physician characteristics were associated with use of antiretroviral drugs. After adjusting for CD4 cell count and HIV-1 RNA level at eligibility, odds of not receiving antiretrovirals were increased more than 2-fold for females (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.08-5.93) and 3-fold for those not currently enrolled in drug or alcohol treatment programs (OR, 3.49; 95% CI, 1.45-8.40). Younger drug users were less likely to receive therapy (OR, 0.47/10-y increase; 95% CI, 0.28-0.80). Those with physicians having the least experience treating persons with HIV infection were more than 5 times less likely to receive therapy (OR, 5.55; 95% CI, 2.49-12.37).

Conclusions.— Despite free antiretroviral therapy, many HIV-infected injection drug users are not receiving it. Public health efforts should target younger and female drug users, and physicians with less experience treating HIV infection.

THE NUMBER of human immunodeficiency virus (HIV)–infected injection drug users (IDUs) recently increased in Vancouver, British Columbia.1,2 Prevalence and incidence of HIV were reported as 25% and 18.6 per 100 person-years, respectively.2 Advances in antiretroviral therapy (ART) have improved survival in British Columbia3 and elsewhere.4,5 Also, treated subjects experiencing decreases in HIV-1 RNA below detectable levels may be less infectious.6,7 Despite this, physicians may be less likely to recommend ART for IDUs because of the belief that IDUs are less adherent to complex regimens, which could promote selection of drug-resistant strains.8 In British Columbia, all HIV-positive persons eligible for ART according to guidelines9,10 have free access to it through a province-wide HIV/AIDS (acquired immunodeficiency syndrome) drug treatment program. To estimate the proportion of eligible IDUs receiving ART, we linked survey data with data from the drug treatment program. We also attempted to identify barriers to ART utilization.

Study Subjects

Beginning in May 1996, 1106 IDUs were recruited into a prospective cohort study through self-referral and street outreach.2 Subjects were eligible if they had injected illicit drugs at least once in the previous month, resided in the greater Vancouver region, and provided written informed consent. Most subjects (82%) were volunteers who had learned of the study via other participants or recruitment materials. Others were referred by storefront agencies (15%) or clinics (3%). At baseline and semiannually, subjects provided blood samples and completed an interviewer-administered questionnaire. Baseline survey data pertained to the previous 6 months and included sociodemographics, physician visits, drug use, and attendance at needle exchanges and drug or alcohol treatment programs. At each visit, CD4 cell counts and plasma HIV-1 RNA levels (Amplicor; Roche Molecular Systems, Branchburg, NJ) were assessed.

Subjects were included if testing HIV positive at cohort entry, aware of HIV status, eligible for ART,9,10 or receiving ART through the program by August 31, 1997. To assess the proportion of eligible subjects receiving ART, nonnominal cohort data were linked to program data. The study was approved by the University of British Columbia and St Paul's Hospital.

HIV/AIDS Drug Treatment Program

Free ART has been available since 1986.3 Since 1992, when double combinations were available for those with CD4 cell count of 0.35 × 109/L (350/µL) or less, ART has been distributed to more than 4000 persons meeting guidelines criteria.9,10 Pharmaceutical sales suggest that less than 1% of HIV-infected British Columbians purchase ART outside the program (Pharmacare, British Columbia Ministry of Health, unpublished data, 1998). Combination therapy access was expanded to those with CD4 cell count of less than 0.50×109/L in December 1995. In July 1996, triple combinations were available to ART-naive persons with CD4 cell count of less than 0.50 × 109/L and/or HIV-1 RNA level higher than 100000 copies/mL, and double combinations to those with CD4 cell count of less than 0.50×109/L and/or HIV-1 RNA level of 5000 to 100000 copies/mL. Physicians enrolling a patient (a Canadian citizen or landed immigrant [may legally reside and work in Canada]) in the program complete a drug request form with which patient baseline and physician data are collected.

Statistical Analysis

Treated and untreated subjects were compared regarding self-reported demographic and behavioral information, using contingency table analysis. Program enrollment data were used to assign a level of physician HIV-related experience for each subject, estimated via cumulative number of patients receiving ART within their practice, by the date of subject's first known eligibility.

To assess independent predictors of never receiving ART, variables significant in univariate analyses (P<.05) were considered for inclusion in a multivariate logistic regression model, adjusting for CD4 cell count and HIV-1 RNA level at eligibility. This model assumed a linear relationship between independent variables and log odds of never receiving ART. The few subjects with missing values were excluded from multivariate models. Corresponding odds ratios (ORs) and test-based 95% confidence intervals (CIs) were computed. All 2-way interactions were evaluated.

Of 191 seropositive IDUs aware of their serostatus, 177 met ART eligibility guidelines. Of these, 71 (40%) had received any ART. Median time since eligibility was 11 months for treated and untreated subjects (P=.10). At entry into the program, 12 (17%) received monotherapy, 47 (66%) double combinations, and 12 (17%) triple therapy. Most (80%) received therapy meeting guidelines at enrollment. We defined adherence as ratio of number of months patients received ART refills relative to total number of months they should have received ART, by which definition 37% were 80% adherent.

Characteristics associated with not receiving therapy are included in Table 1. The CD4 cell count and HIV-1 RNA level did not differ at eligibility for untreated and subsequently treated subjects. Groups did not differ by self-reported drug use, housing, or needle exchange program attendance. Compared with other IDUs receiving ART, no significant differences emerged regarding gender, age, CD4 cell count, or HIV-1 RNA level (P>.05).

Table Graphic Jump LocationTable 1.—Characteristics of Injection Drug Users Receiving and Not Receiving Antiretroviral Therapy*

After simultaneously adjusting for CD4 cell count and HIV-1 RNA level at eligibility, patient and physician characteristics were associated with ART use (Table 2). A multivariate logistic regression model showed more than 2-fold increased odds of not receiving ART for females, and 3-fold increased odds for IDUs not currently enrolled in drug or alcohol treatment programs. Younger IDUs were less likely to receive ART. Those with physicians having the lowest level of HIV experience were more than 5 times less likely to receive ART. Results were unchanged after adjusting for time since eligibility and other factors. No significant interactions emerged.

Table Graphic Jump LocationTable 2.—Multivariate Logistic Regression Analysis of Variables Asociated With Not Receiving Antiretroviral Therapy Among 177 Eligible HIV-Infected Injection Drug Users*

Despite free ART in British Columbia, less than half the IDUs in our sample received therapy about 1 year after becoming eligible. After accounting for CD4 cell count and HIV-1 RNA level, barriers to ART use included both physician and patient characteristics, suggesting that a multifaceted approach is needed to maximize ART use.

Physicians with the least ART experience were more than 5 times less likely to prescribe ART for IDUs, relative to most experienced physicians. Physician HIV/AIDS experience was substantially associated with patient survival in prior reports.11,12 Previously, we showed that physician experience was associated with practice concordance with therapeutic HIV/AIDS guidelines.13 Also, motivated IDUs may select physicians with a higher HIV/AIDS caseload.

One could argue that the low overall ART uptake seen reflected exclusion of less adherent patients by physicians, possibly related to the association between enrollment in drug or alcohol treatment programs and ART use. However, we found no markers of social instability such as income assistance, unstable housing, or incarceration associated with ART use.

Injection drug users not enrolled in drug or alcohol treatment programs were 3 times less likely to receive ART. These IDUs may be less concerned about their health, and less willing to initiate ART. Also, rehabilitation programs may facilitate access to clinicians who are more likely to prescribe ART. Similar findings were reported regarding IDUs offered zidovudine and opportunistic infection prophylaxis in Connecticut.14 Drug abstinence was also associated with receiving ART in a study in Baltimore, Md.15

Young IDUs were less likely to receive ART. They may be less aware of ART benefits, and less likely to seek care. Alternatively, clinicians may be less likely to prescribe ART for them if they perceive that young IDUs are less able to adhere to complex regimens.

Female IDUs were twice less likely to receive ART than males after adjusting for baseline characteristics. In prior reports, females were less likely than males to receive zidovudine after accounting for clinical and sociodemographic variables.16,17 Although some US studies did not find sex to significantly predict health service use in HIV infection,15,18 a study of persons with AIDS found that females were less likely to use health care services such as hospitalization than were males.19 In our cohort, females with HIV infection reported higher use of hospital and emergency department services than did males with infection,20 suggesting that differential access to care cannot explain sex differences in ART use.

A limitation of our analysis is the inability to explore reasons for patient- and physician-specific barriers to ART use. It is possible that in the clinical judgment of the physician, prescribing ART would have been inappropriate in certain situations. Also, physicians may have prescribed treatment that was not taken. In subsequent analyses of 120 of the 177 subjects, 94 (78.3%) were given a prescription for ART and 48 (51.1%) had it filled. Although not necessarily generalizable, these figures support the findings reported herein. Since subjects were largely volunteers and tended to belong to the lowest socioeconomic strata, caution should be exercised in generalizing results. However, demographic characteristics of subjects did not differ from those of other IDUs in the drug treatment program. We may have overestimated the proportion of IDUs receiving ART, as some subjects may have been referred for therapy because of study participation. As this is a cross-sectional analysis, we cannot infer causal relationships. Although recall bias may have influenced self-reports, data pertaining to physician HIV experience and ART use were obtained independently from the drug treatment program.

Studies in the United States indicate that ART access may be limited by lack of third-party reimbursement.15,16,21 We found that barriers to ART use persist in IDUs with HIV infection, despite universal health care and free ART. Less experienced physicians and subgroups such as female and young IDUs may require targeted interventions to increase access to effective HIV treatment to enhance survival and possibly decrease risk of HIV transmission.

Patrick DM, Strathdee SA, Archibald CP.  et al.  Determinants of HIV seroconversion in injection drug users during a period of rising prevalence in Vancouver.  Int J STD AIDS.1997;8:437-445.
Strathdee SA, Patrick DM, Currie SL.  et al.  Needle exchange is not enough.  AIDS.1997;11:F59-F65.
Hogg RS, Heath KV, Yip B.  et al.  Improved survival among HIV-infected individuals.  JAMA.1998;279:450-454.
Hammer SM, Squires KE, Hughes MD.  et al.  A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less.  N Engl J Med.1997;337:725-733.
Palella Jr FJ, Delaney KM, Moorman AC.  et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.  N Engl J Med.1998;338:853-860.
Vernazza PL, Gilliam BL, Flepp M.  et al.  Effect of antiviral treatment on the shedding of HIV-1 in semen.  AIDS.1997;11:1249-1254.
Cardo DM, Culver DH, Ciesielski CA.  et al.  A case-control study of HIV seroconversion in health care workers after percutaneous exposure.  N Engl J Med.1997;337:1485-1490.
Bangsberg D, Tulsky JP, Hecht RM, Moss AR. Protease inhibitors in the homeless.  JAMA.1997;278:63-65.
Carpenter CCJ, Fischl MA, Hammer SM.  et al.  Antiretroviral therapy for HIV infection in 1997: updated recommendations of the International AIDS Society–USA Panel.  JAMA.1997;277:1962-1969.
Montaner JSG, O'Shaughnessy MV. Therapeutic Guidelines for the Treatment of HIV/AIDS and Related Conditions . Vancouver: British Columbia Centre for Excellence in HIV/AIDS; 1996.
Markson LE, Cosler LE, Turner BJ. Implications of generalists' slow adoption of zidovudine in clinical practice.  Arch Intern Med.1994;154:1497-1504.
Kitahata MM, Koepsell TD, Deyo RA, Maxwell CI, Dodge WT, Wagner EH. Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival.  N Engl J Med.1996;334:701-706.
Heath KV, Hogg RS, Singer J, Schechter MT, O'Shaughnessy MV, Montaner JS. Adherence to clinical guidelines for the therapeutic management of HIV disease.  Clin Invest Med.1997;20:381-387.
O'Connor PG, Molde S, Henry S, Schockcor WT, Schottenfeld RS. Human immunodeficiency virus infection in intravenous drug users: a model for primary care.  Am J Med.1992;93:382-386.
Celentano DD, Vlahov D, Cohn S, Shadle VM, Olugbenga O, Moore RD. Self-reported antiretroviral therapy in injection drug users.  JAMA.1998;280:544-546.
Moore RD, Stanton D, Gopalan R, Chaisson RE. Racial differences in the use of drug therapy for HIV disease in an urban community.  N Engl J Med.1994;330:763-768.
Stein MD, Piette J, Mor V.  et al.  Differences in access to zidovudine (AZT) among symptomatic HIV-infected persons.  J Gen Intern Med.1991;6:35-40.
Mor V, Fleishman JA, Dresser M, Piette J. Variation in health service use among HIV-infected patients.  Med Care.1992;30:17-29.
Hellinger FJ. The use of health services by women with HIV infection.  Health Serv Res.1993;28:543-561.
Palepu A, Strathdee SA, Anis AH.  et al.  Health services utilization in a cohort of injection drug users.  Can J Infect Dis.1997;8:27A.
Graham NM, Jacobson LP, Kuo V, Chmiel JS, Morgenstern H, Zucconi SL. Access to therapy in the Multicenter AIDS Cohort Study, 1989-1992.  J Clin Epidemiol.1994;47:1003-1012.

Figures

Tables

Table Graphic Jump LocationTable 1.—Characteristics of Injection Drug Users Receiving and Not Receiving Antiretroviral Therapy*
Table Graphic Jump LocationTable 2.—Multivariate Logistic Regression Analysis of Variables Asociated With Not Receiving Antiretroviral Therapy Among 177 Eligible HIV-Infected Injection Drug Users*

References

Patrick DM, Strathdee SA, Archibald CP.  et al.  Determinants of HIV seroconversion in injection drug users during a period of rising prevalence in Vancouver.  Int J STD AIDS.1997;8:437-445.
Strathdee SA, Patrick DM, Currie SL.  et al.  Needle exchange is not enough.  AIDS.1997;11:F59-F65.
Hogg RS, Heath KV, Yip B.  et al.  Improved survival among HIV-infected individuals.  JAMA.1998;279:450-454.
Hammer SM, Squires KE, Hughes MD.  et al.  A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less.  N Engl J Med.1997;337:725-733.
Palella Jr FJ, Delaney KM, Moorman AC.  et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.  N Engl J Med.1998;338:853-860.
Vernazza PL, Gilliam BL, Flepp M.  et al.  Effect of antiviral treatment on the shedding of HIV-1 in semen.  AIDS.1997;11:1249-1254.
Cardo DM, Culver DH, Ciesielski CA.  et al.  A case-control study of HIV seroconversion in health care workers after percutaneous exposure.  N Engl J Med.1997;337:1485-1490.
Bangsberg D, Tulsky JP, Hecht RM, Moss AR. Protease inhibitors in the homeless.  JAMA.1997;278:63-65.
Carpenter CCJ, Fischl MA, Hammer SM.  et al.  Antiretroviral therapy for HIV infection in 1997: updated recommendations of the International AIDS Society–USA Panel.  JAMA.1997;277:1962-1969.
Montaner JSG, O'Shaughnessy MV. Therapeutic Guidelines for the Treatment of HIV/AIDS and Related Conditions . Vancouver: British Columbia Centre for Excellence in HIV/AIDS; 1996.
Markson LE, Cosler LE, Turner BJ. Implications of generalists' slow adoption of zidovudine in clinical practice.  Arch Intern Med.1994;154:1497-1504.
Kitahata MM, Koepsell TD, Deyo RA, Maxwell CI, Dodge WT, Wagner EH. Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival.  N Engl J Med.1996;334:701-706.
Heath KV, Hogg RS, Singer J, Schechter MT, O'Shaughnessy MV, Montaner JS. Adherence to clinical guidelines for the therapeutic management of HIV disease.  Clin Invest Med.1997;20:381-387.
O'Connor PG, Molde S, Henry S, Schockcor WT, Schottenfeld RS. Human immunodeficiency virus infection in intravenous drug users: a model for primary care.  Am J Med.1992;93:382-386.
Celentano DD, Vlahov D, Cohn S, Shadle VM, Olugbenga O, Moore RD. Self-reported antiretroviral therapy in injection drug users.  JAMA.1998;280:544-546.
Moore RD, Stanton D, Gopalan R, Chaisson RE. Racial differences in the use of drug therapy for HIV disease in an urban community.  N Engl J Med.1994;330:763-768.
Stein MD, Piette J, Mor V.  et al.  Differences in access to zidovudine (AZT) among symptomatic HIV-infected persons.  J Gen Intern Med.1991;6:35-40.
Mor V, Fleishman JA, Dresser M, Piette J. Variation in health service use among HIV-infected patients.  Med Care.1992;30:17-29.
Hellinger FJ. The use of health services by women with HIV infection.  Health Serv Res.1993;28:543-561.
Palepu A, Strathdee SA, Anis AH.  et al.  Health services utilization in a cohort of injection drug users.  Can J Infect Dis.1997;8:27A.
Graham NM, Jacobson LP, Kuo V, Chmiel JS, Morgenstern H, Zucconi SL. Access to therapy in the Multicenter AIDS Cohort Study, 1989-1992.  J Clin Epidemiol.1994;47:1003-1012.
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