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AIDS Care: Psychological and Sociomedical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20
Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users a
b
c
A. B. Williams , E. A. McNelly , A. E. Williams & R. T. D'Aquila a
Yale School of Nursing ,
b
APT Foundation, New Haven Connecticut
c
Jerome Holland Labs, American Red Cross ,
d
d
Infectious Disease Unit , Massachusetts General Hospital and Harvard Medical School , USA Published online: 25 Sep 2007.
To cite this article: A. B. Williams , E. A. McNelly , A. E. Williams & R. T. D'Aquila (1992) Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 4:1, 35-41, DOI: 10.1080/09540129208251618 To link to this article: http://dx.doi.org/10.1080/09540129208251618
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Downloaded by [University of Cambridge] at 18:44 25 December 2014
Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
AIDS CARE, VOL. 4, NO. 1, 1992
35
Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users
Downloaded by [University of Cambridge] at 18:44 25 December 2014
A. B. WILLIAMS, E. A. MCNELLY', A. E. WILLIAMS^ & R. T. D'AQUILA3 Yale School of Nursing, ' A P T Foundation, New Haven Connecticut, 2Jerome Holland Labs, American Red Cross G, 31nfectiousDisease Unit, Massachusetts General Hospital and Hamard Medical School, USA
Abstract This study examined whether methadone maintenance treatment decreases drug injection enough to significantly limit HIV-1 transmission among injection drug users (IDU). When HIV-1 seroconversion status among prospectively followed methadone maintenance clients was analyzed by treatment retention, 1/56 (2%) of those who remained continuously in treatment seroconverted while 8/42 (19%) of those whose methadone treatment was interrupted seroconverted. When controlled for length of follow up, the difference in seroconversion rate was not statistically significant. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years (95% Confidence Interval [CIJ = 0.1, 5.3) and those with interrupted treatment a rate of 4.3 per 100 person years (95% CI = 2.2, 8.6). Subjects in continuous treatment reported less needle sharing (p < 0.0002), fewer needle sharingpartners (p < 0.002), fewer sexual partners (p < 0.03), and were more likely to be women (p < 0.01). These data indicate the need for larger studies to evaluate both client and drug treatment program characteristics which might concomitantly increase treatment retention and decrease HIV-1 risk.
Introduction Human immunodeficiency virus-type 1 (HIV-1) infection is a growing problem among injection drug users (IDU), their sexual partners, and their children in many parts of the world. HIV-1 infection is well established in Italian and Spanish IDU and is spreading rapidly in Poland, where IDU represent 64% of seropositive individuals identified between 1986 and 1989 (Stapinski et al., 1990). In the United States seroprevalence rates among IDU range from 0-65% (Hahn et al., 1989); and transmission from IDU to their sexual partners is responsible for an alarming increase in HIV-1 infection among US woman and children.
Address for correspondence: Ann B. Williams, Adult Health Division, Yale School of Nursing, P.O. Box 9740, New Haven, CT 06536-0740, USA.
Downloaded by [University of Cambridge] at 18:44 25 December 2014
36
A. B. WILLIAMS ET AL.
HIV-1 infection in IDU is associated with both frequency of needle use (D’Aquila et el., 1989; Marmor et al., 1987; Schoenbaum et al., 1989; Williams, et al., 1987) and with number of needle sharing contacts (Chaisson et al., 1987; Schoenbaum et al., 1989). Many countries have sought to reduce the risk associated with needle sharing through the provision of needles, syringes and other injecting equipment to IDU (Hartgers et al., 1989; van den Hoek, 1989; Stimson, 1989). Methadone maintenance programs may also reduce the risk for HIV- 1 transmission through reducing the frequency of drug injection. Methadone maintenance programs can achieve substantial reductions in illicit drug consumption (Gerstein & Lewin, 1990; Hubbard et al., 1988; Hubbard et al., 1989) and decrease both injection drug use and needle sharing among participants (Ball et al., 1988; Robert et al., 1990). However, it is not clear that these accomplishments lead to a subsequent decrease in the risk of HIV-1 acquisition among IDU in methadone maintenance. Some patients on methadone maintenance persist in illicit drug use despite adequate serum methadone levels (Bell et al., 1990); and methadone maintenance programs may not decrease injection drug use to the extent necessary to make a significant impact on the HIV1 epidemic, since a single exposure to HIV-1 contaminated drug injection equipment can be sufficient to transmit infection. Cross-sectional studies in the United States have suggested a decreased risk for HIV-1 associated with methadone treatment (Chaisson et al., 1989; Marmor et al., 1987; Schoenbaum et al., 1989; Williams et al., 1990). Similarly, in northern Italy, the proportion of drug users attending methadone programs was inversely associated with cumulative AIDS incidence (Serraino & Francheschi, 1989). But in Rome no difference in the rate of HIV-1 seroprevalence was detected between IDUs in methadone treatment and those just entering treatment (Zaccarelli et al., 1990); and long term methadone users in Amsterdam had a similar risk for HIV-1 infection as other IDUs (Hartgers et al., 1990). More data are needed to determine if directing scarce public monies into methadone maintenance programs will limit the epidemic of HIV-1 among IDUs, their sexual partners and children. T o that end, we examined HIV-1 seroconversion rates among IDUs both in, and out of, methadone maintenance treatment. The study was approved by the institutional review board for the protection of human subjects at Yale School of Medicine.
Methods Setting
The study was conducted at a long term methadone maintenance program in New Haven, Connecticut, serving approximately 400 clients whose average duration of treatment is five years. Methadone maintenance program admission criteria include a one year history of narcotic use, evidence of current physiological dependence on opiates, and 18 years of age. Seventy percent of program clients are Caucasians; 29% are African-Americans; and 1% are other, including Hispanics. Two thirds of the program population are male and one third female. The methadone program offers a wide range of services; all participants receive frequent contact with mental health clinicians, monitoring of urine specimens for illicit substance use, mandatory weekly groups or individual therapy sessions, and primary health care services. AIDS related services available to all program members include pre- and posttest HIV counseling, confidential HIV test, AIDS risk reduction education, and HIV related health care. This methadone program imposes relatively strict guidelines for program participation and for client continuation in treatment. Compliance with clearly defined program rules is
METHADONE MAINTENANCE TREATMENT AND HIV
37
expected, and repeated infractions result in expulsion from the program. Methadone maintenance doses vary, but average 70 milligrams. During the course of this study, there was a waiting list of approximately 3-4 months for program admission.
Downloaded by [University of Cambridge] at 18:44 25 December 2014
Subjects Individuals who were past or current clients of the methadone maintenance program, were over 18 years of age, and had a personal history of injection drug use were invited to participate in this prospective study of HIV-1 seroconversion if they also met one of the following three criteria: (1) had participated in a 1982-83 study of hepatitis and had an identifiable serum sample from that study in our serum bank; (2) had been in the methadone program consistently since 1982; or (3) entered the methadone program between October, 1985, and July, 1988. Entry into the 1982-83 hepatitis study required mild transaminase elevations without serologic evidence of active hepatitis B infection at the time of that study (1982-83). Seventy seven percent (133/173) of the subjects in the 1982-83 study were located; 54% (56/104) of those who were eligible agreed to participate. The remaining 42 subjects met criteria (2) or (3). Subjects were excluded if they did not wish to be tested for HIV-1 and informed of the test results. Anonymous HIV-1 testing was available throughout the course of the study to all methadone clients, regardless of study participation.
Data collection HIV-1 serum antibody status was determined at enrollment and on follow-up visits. Positive enzyme-linked immunoassays (EIA) were confirmed by immuno-blot (IB) analysis. Reactivity to env and gag or pol proteins were the criteria for positivity. Stored sera specimens were also tested for those subjects who had participated in the earlier (1982-1983) hepatitis study. An interview questionnaire administered on enrollment collected demographic information and self-reported drug use and sexual behaviors. Methadone program treatment histories including duration and dates of treatment, were determined by review of program records. Subjects returned every six months for repeat HIV-1 testing and a brief follow up interview.
Data analysis The association of each variable with HIV-1 serologic status was examined and comparisons of demographic and behavioral variables were made between subjects grouped by treatment history. Univariate analysis was performed using unpaired t-tests for ordinal variables and contingency table analysis using chi-square with continuity correction or Fisher’s exact test for nominal and categorical variables in two by two tables. HIV-1 seroconversion rates per person year were calculated. Odds ratios and 95% confidence intervals were used to provide a measure of association between HIV-1 antibody status and specific variables.
Results Ninety-eight subjects were HIV-1 seronegative at baseline and completed at least one follow-up visit with repeat serologic testing. The follow-up period varied by subject and was defined as the time between study enrollment with a negative HIV-1 EIA and the first IB-
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38
A. B. WILLIAMS ET AL.
confirmed positive HIV-1 EIA or the final study visit if the subject continued to test negative. For those subjects who had stored sera available from the earlier hepatitis study, the follow-up period began with the date of the initial negative HIV-1 EIA in 1982-83. There were 62 (63%) men and 36 (37%) women. Eighty one (83%) were Caucasian Americans and 17 (1 7%) were African-Americans. There were no Hispanics in this study. The mean age was 35 years [Range (R) = 24-58]. All subjects reported only heterosexual activity. Mean age at first injection drug use was 19 years (R = 12-33). Length of injection drug use was obtained by subtracting age at first injection from current age; the mean length of injection drug use was 16 years (R = 3-38). Forty-seven (48%) reported that they shared drug injection equipment during the study period. Of those who had shared equipment, 36% (17147) had shared with only one person. Two subjects had shared injection equipment with more than 10 individuals. Twelve subjects reported that they used local shooting galleries during the study period; none reported using shooting galleries in New York or New Jersey. During the study period, subjects received a mean of 27 months of methadone maintenance treatment (R = 0-84). We also looked at whether or not subjects had left and then re-entered methadone maintenance treatment during the follow-up time. Fifty-six (57%) of the subjects received one uninterrupted treatment episode during the study period; we called this the Continuous Treatment Group. Forty-two (43%) subjects were not in treatment at all, left treatment, or left and returned to treatment during the study period; they made up the Interrupted Treatment Group.
HIV-1 seroconversion Ninety-eight subjects were followed for a mean of 39 months (R = 7-89). Nine subjects (10%) became IB-confirmed HIV-1 EIA positive during the study period, and 89 remained HIV-1 EIA negative. The seroconversion rate was 2.8 per 100 person years. On univariate analysis, HIV-1 seroconverters did not differ from those who remained HIV- 1 seronegative according to the demographic variables of age, sex, race or employment status. Nor were there significant differences in number of sexual partners during the study period, age at first drug use, length of injection drug use, use of shooting galleries, whether or not needles were shared in the past year, the number of individuals with whom needles were shared, or the total amount of time spent in the methadone program during the study period (Table 1). Subjects who remained on methadone maintenance without interruption during the follow-up period (Continuous Treatment Group) were less likely to seroconvert than those in the Interrupted Treatment Group. One of 56 (2%) subjects in the Continuous Treatment Group seroconverted during the follow-up period. Eight of 42 (19%) subjects in the Interrupted Treatment Group seroconverted [odds ratio (OR) = 12.9, 95% confidence interval (CI) = 1.6 and 584, p = 0.0045, Fisher’s Exact]. Total length of study follow-up differed for the two groups. Subjects in the Continuous Treatment Group were followed for a mean of 29 months (R = 7-84, Median = 17); while subjects in the Interrupted Group were followed for a mean of 53 months (R = 8-89, Median = 57). Therefore, the seroconversion rate per person year was computed for each of the two groups. For the Continuous Treatment Group, the HIV-1 seroconversion rate was 0.7 per 100 person years (95% CI = 0.1 and 5.3). For the Interrupted Treatment Group, the HIV-1 seroconversion rate was 4.3 per 100 person years (95% CI = 2.2 and 8.6). The difference between seroconversion rates for the two groups was not significant (Z = 1.65, p = 0.10, two-sided). Subjects in the Continuous Treatment Group were less likely to have
METHADONE MAINTENANCE TREATMENT AND HIV
39
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Table 1. Demographic and behavioral characteristics of subjects by HIV-1antibody status at conclusion of study n* Variable
HIV-positive
HIV-negative
p-value
98 Mean age 98 Sex Male Female 98 Race Caucasian African-American 85 Employment StaNS Employed Unemployed 95 Number of sexual partners during study 0 1 2-5 6+ 98 Mean age at first injection drug use 98 Mean years of injection drug use 97 Shooting gallery use Used galleries Did not use galleries 97 Needle sharing in past year Shared needles Did not share needles 88 Number of needle sharing partners in past year 0 1 2-5 6 f 98 Mean months of methadone during study period 98 Continuity of methadone treatment Continuous Interrupted
39 years
35 years
0.llt
6 3
56 33
0.894
6 3
75 14
0.39$
2 6
38 39
0.354
6 46 29 5 20 years 16
0.08t
1 8
11 77
0.684
6 3
41 47
0.45$
3 1 3 1 30
47 16 12 5 27
0.34$ 0.67t
1 8
55 34
0.01$
2 5 1 1 19 years 20
0.264 0.72t
* Number of subjects for whom data were available.
t Unpaired t-test, two-tailed.
$ Chi-square with continuity correction.
shared needles in the past year (p = 0.0002, chi-square), reported fewer needle sharing partners (p = 0.002, chi-square) and fewer sexual partners (p = 0.03, chi-square), and were more likely to be women (p = 0.01) (Table 2). Discussion
In this study, subjects in continuous methadone treatment had a non-significant trend toward a lower HIV- 1 seroconversion rate than subjects whose treatment was interrupted. Subjects in continuous treatment were significantly more likely to be women and reported significantly fewer needle sharing and sexual partners than subjects with interrupted treatment. However, HIV- 1 seroconversion was not associated with gender or with reported number of sexual partners or needle sharing partners (Table 1). Therefore, it seems unlikely that the trend seen here toward fewer HIV-1 seroconversions in the continuous treatment group was due to confounding by these factors. However, the small number of subjects as
40
A. B. WILLIAMS ETAL. Table 2. Demographic and behavioral characteristics of subjects by continuity of treatment experience
n* Variable
Continuous
Interrupted
Mean age Sex Male Female 98 Race Caucasian African-American 85 Employment status Emp 1oy ed U nemp 1oy ed 95 Number of sexual partners during study
36 years
35 years
0.60t
29 27
33 9
0.01*
48 8
33 9
0.35$
26 27
14 18
0.80f
4 36 11 3 19 years 16
4 15 19 3 19 years 16
0.03$ 0.71t 0.79t
4 51
8 34
0.154
17 38
30 12
0.0002$
38 9 4
12 8 11 4 42
0.002* 0.55t
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98 98
0 1 2-5 6+
Mean age at first injection drug use Mean years of injection drug use Shooting gallery use Used galleries Did not use galleries 97 Needle sharing in past year Shared needles Did not share needles 88 Number of needle sharing partners in past year 98 98 97
0 1 2-5 6-t 98
*
Mean months of methadone during study period
2 56
p-value
Number of subjects for whom data were available. two-tailed. Chi-square with continuity correction.
t Unpaired t-test,
well as the relatively shorter length of follow up for those in continuous treatment limits the analysis. Larger studies with longer duration of follow up are needed to determine if the suggestion in these data that methadone maintenance treatment lowers HIV- 1 seroconversion risk is true. Such studies should also address the possibility that the same factors which enabled subjects to remain in methadone treatment also enabled them to better protect themselves from HIV- 1 infection. Identification of specific client-associated or programassociated factors affecting both methadone treatment retention and HIV- 1 risk could guide program planners in targeting scarce resources. The data presented here indicate the need for further study and suggest that clients with interrupted treatment histories should be among the priority targets for HIV-1 risk reduction education while we continue the search for more effective treatment for both drug addiction and HIV-1 infection.
Acknowledgements This work was supported by Grant DAO 330-02 from the National Institute on Drug Abuse. We thank the clients and staff of the APT Foundation Methadone Programs for their
METHADONE MAINTENANCE TREATMENT AND HIV
41
participation in this study, Mark Hayes and Martin Waugh for enthusiastic help with data collection, and Dr Peter Bacchetti for statistical consultation.
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References BALL,J.C., LANGE,W.R., MYERS,C.P. & FRIEDMAN, S. (1988) Reducing the risk of AIDS through methadone maintenance treatment, Journal of Health and Social Behaaior, 29, pp. 214-226. BELL,J., BOWRON, P., LEWIS,J. & BATEY,R. (1990) Serum levels of methadone in maintenance clients who persist in illicit drug use, British Journal of Addiction, 85, pp. 1599-1602. CHAISSON, R.E., BACCHETTI, P., OSMOND,D., BRODIE,B., SANDE,M. & MOSS,A.R. (1989) Cocaine use and HIV infection in intravenous drug users in San Francisco, JAMA, 261, pp. 561-565. CHAISSON,R.E., MOSS, A.R., ONISHI, R., OSMOND,D. & CARLSON,J. (1987) Human immunodeficiency virus infection in heterosexual intravenous drug users in San Francisco, American Journal of Public Health, 77, pp. 169-1 72. D’AQUILA,R.T., PETERSON,L.R., WILLIAMS, A.B. & WILLIAMS,A.E. (1989) Racelethnicity as a risk factor for HIV-1 infection among Connecticut intravenous drug users, ’Journal of Acquired Immune Deficiency Syndmrnes, 2, pp. 503-513. GERSTEIN,D.R. & LEWIN,L.S. (1990) Treating drug problems, New England ’Journal of Medicine, 323, pp. 844-848. HAHN,R.A., ONORATO, I.M., JONES,T.S. & DOUGHERY, J. (1989) Prevalence of HIV infection among intravenous drug users in the United States, J A M , 261, pp. 2677-2684. HARTGERS, C., BUNING,E.C., VAN SANTEN,G.W., VERSTER,A.D. & COUTINHO,R.A. (1989) The impact of the needle and syringe-exchange programme in Amsterdam on injecting risk behavior, AIDS, 3, pp. 571-576. HARTGERS, C., VAN DEN HOEK,J., KRIJNEN,P. & COUTINHO,R. (1990) Risk factors and heroin and cocaine use trends among injecting drug users (IDU) in low threshold methadone programs, Amsterdam, 1985-1989, Abstracts of the Sixth International Conference on AIDS, Book 2 (pp. 240) (San Francisco, University of California). HUBBARD, R.L., MARSDEN,M.E., CAVANAUGH, E., RACHEL,J.V. & GINZBURG, H.M. (1988) Role of drug-abuse treatment in limiting the spread of AIDS, Rewiews OfInfectious Diseases, 10, pp. 377-384. HUBBARD,R.L., MARSDEN,M.E., RACHAL,J.V., HARWOOD, H.J., CAVANAUGH, E.R. & GINZBURG,H.M. (1989) Drug Abuse Treatment: A National Study of Effectiaeness (Chapel Hill, University of North Carolina Press). MARMOR,M., DISJARLAIS, D.C., COHEN,H., FRIEDMAN, S.R., BEATRICE,S.T., DUBIN,N. et al. (1987) Risk Factors for infection with human immunodeficiency virus among intravenous drug abusers in New York City, AIDS, 1, pp, 39-44. ROBERT,C.F., D’EGLON,J.J., WINTSCH,J., MARTIN,J.L., PERRIN, L., BOURQUIN,M. et al. (1990) Behavioural changes in intravenous drug users in Geneva: rise and fall of HIV infection, 1980-1989, AIDS, 4, pp. 657-660. SCHOENBAUM, E.E., HARTEL,D., SELWYN,P., KLEIN,R.S., DAVENNY, K., ROGERS,M. et al. (1989) Risk factors for human immunodeficiency virus infection in intravenous drug users, New England Journal of Medicine, 321, pp. 874-879. SERRAINO, D. & FRANCHESCHI, S. (1989) Methadone maintenance programs and AIDS, Lancet, ii, pp. 1522-1523. STAPINSKI,A,, MAZURKIEWICZ, W. & OCHELSKA,B. (1990) HIV infection in intravenous drug users in Poland, Abstracts of the Sixth International Conference on AIDS, Book 2 (p. 241) (San Francisco, University of California). STIMSON,G. (1989) Syringe-exchange programmes for injecting drug users, AIDS, 3, pp. 253-260. VANDEN HOEK,J.A.R., VAN HAASTRECHT, M.S. & COUTINHO, R.A. (1989) Risk reduction among intravenous drug users in Amsterdam under the influence of AIDS, American Journal of Public Health, 79, pp. 1355-1357. WILLIAMS,A.B., D’AQUILA,R.T. & WILLIAMS,A.E. (1987) HIV infection in intravenous drug users, IMAGE, 19, pp. 179-183. WILLIAMS,A.B., VRANIZAN,K., GORTER,R., BRODIE,B., MEAKIN, R. & Moss, A.R. (1990) Methadone maintenance, HIV serostatus and race in injection drug users in San Francisco, California, Abstracts of the Sixth International Conference on AIDS, Book 3 (p. 276) (San Francisco, University of California). ZACCARELLI, M., REZZA,G., GIRARDI,E., PURO, V., GATTARI, P., PEZZOTTI,P. et al. (1990) Using different indicators in assessing HIV trends in injecting drug users, Abstracts of the Sixth International Conference on AIDS, Book 2 (pp. 238) (San Francisco, University of California).
AIDS Care: Psychological and Sociomedical Aspects of AIDS/HIV Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/caic20
Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users a
b
c
A. B. Williams , E. A. McNelly , A. E. Williams & R. T. D'Aquila a
Yale School of Nursing ,
b
APT Foundation, New Haven Connecticut
c
Jerome Holland Labs, American Red Cross ,
d
d
Infectious Disease Unit , Massachusetts General Hospital and Harvard Medical School , USA Published online: 25 Sep 2007.
To cite this article: A. B. Williams , E. A. McNelly , A. E. Williams & R. T. D'Aquila (1992) Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users, AIDS Care: Psychological and Socio-medical Aspects of AIDS/HIV, 4:1, 35-41, DOI: 10.1080/09540129208251618 To link to this article: http://dx.doi.org/10.1080/09540129208251618
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Downloaded by [University of Cambridge] at 18:44 25 December 2014
Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
AIDS CARE, VOL. 4, NO. 1, 1992
35
Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users
Downloaded by [University of Cambridge] at 18:44 25 December 2014
A. B. WILLIAMS, E. A. MCNELLY', A. E. WILLIAMS^ & R. T. D'AQUILA3 Yale School of Nursing, ' A P T Foundation, New Haven Connecticut, 2Jerome Holland Labs, American Red Cross G, 31nfectiousDisease Unit, Massachusetts General Hospital and Hamard Medical School, USA
Abstract This study examined whether methadone maintenance treatment decreases drug injection enough to significantly limit HIV-1 transmission among injection drug users (IDU). When HIV-1 seroconversion status among prospectively followed methadone maintenance clients was analyzed by treatment retention, 1/56 (2%) of those who remained continuously in treatment seroconverted while 8/42 (19%) of those whose methadone treatment was interrupted seroconverted. When controlled for length of follow up, the difference in seroconversion rate was not statistically significant. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years (95% Confidence Interval [CIJ = 0.1, 5.3) and those with interrupted treatment a rate of 4.3 per 100 person years (95% CI = 2.2, 8.6). Subjects in continuous treatment reported less needle sharing (p < 0.0002), fewer needle sharingpartners (p < 0.002), fewer sexual partners (p < 0.03), and were more likely to be women (p < 0.01). These data indicate the need for larger studies to evaluate both client and drug treatment program characteristics which might concomitantly increase treatment retention and decrease HIV-1 risk.
Introduction Human immunodeficiency virus-type 1 (HIV-1) infection is a growing problem among injection drug users (IDU), their sexual partners, and their children in many parts of the world. HIV-1 infection is well established in Italian and Spanish IDU and is spreading rapidly in Poland, where IDU represent 64% of seropositive individuals identified between 1986 and 1989 (Stapinski et al., 1990). In the United States seroprevalence rates among IDU range from 0-65% (Hahn et al., 1989); and transmission from IDU to their sexual partners is responsible for an alarming increase in HIV-1 infection among US woman and children.
Address for correspondence: Ann B. Williams, Adult Health Division, Yale School of Nursing, P.O. Box 9740, New Haven, CT 06536-0740, USA.
Downloaded by [University of Cambridge] at 18:44 25 December 2014
36
A. B. WILLIAMS ET AL.
HIV-1 infection in IDU is associated with both frequency of needle use (D’Aquila et el., 1989; Marmor et al., 1987; Schoenbaum et al., 1989; Williams, et al., 1987) and with number of needle sharing contacts (Chaisson et al., 1987; Schoenbaum et al., 1989). Many countries have sought to reduce the risk associated with needle sharing through the provision of needles, syringes and other injecting equipment to IDU (Hartgers et al., 1989; van den Hoek, 1989; Stimson, 1989). Methadone maintenance programs may also reduce the risk for HIV- 1 transmission through reducing the frequency of drug injection. Methadone maintenance programs can achieve substantial reductions in illicit drug consumption (Gerstein & Lewin, 1990; Hubbard et al., 1988; Hubbard et al., 1989) and decrease both injection drug use and needle sharing among participants (Ball et al., 1988; Robert et al., 1990). However, it is not clear that these accomplishments lead to a subsequent decrease in the risk of HIV-1 acquisition among IDU in methadone maintenance. Some patients on methadone maintenance persist in illicit drug use despite adequate serum methadone levels (Bell et al., 1990); and methadone maintenance programs may not decrease injection drug use to the extent necessary to make a significant impact on the HIV1 epidemic, since a single exposure to HIV-1 contaminated drug injection equipment can be sufficient to transmit infection. Cross-sectional studies in the United States have suggested a decreased risk for HIV-1 associated with methadone treatment (Chaisson et al., 1989; Marmor et al., 1987; Schoenbaum et al., 1989; Williams et al., 1990). Similarly, in northern Italy, the proportion of drug users attending methadone programs was inversely associated with cumulative AIDS incidence (Serraino & Francheschi, 1989). But in Rome no difference in the rate of HIV-1 seroprevalence was detected between IDUs in methadone treatment and those just entering treatment (Zaccarelli et al., 1990); and long term methadone users in Amsterdam had a similar risk for HIV-1 infection as other IDUs (Hartgers et al., 1990). More data are needed to determine if directing scarce public monies into methadone maintenance programs will limit the epidemic of HIV-1 among IDUs, their sexual partners and children. T o that end, we examined HIV-1 seroconversion rates among IDUs both in, and out of, methadone maintenance treatment. The study was approved by the institutional review board for the protection of human subjects at Yale School of Medicine.
Methods Setting
The study was conducted at a long term methadone maintenance program in New Haven, Connecticut, serving approximately 400 clients whose average duration of treatment is five years. Methadone maintenance program admission criteria include a one year history of narcotic use, evidence of current physiological dependence on opiates, and 18 years of age. Seventy percent of program clients are Caucasians; 29% are African-Americans; and 1% are other, including Hispanics. Two thirds of the program population are male and one third female. The methadone program offers a wide range of services; all participants receive frequent contact with mental health clinicians, monitoring of urine specimens for illicit substance use, mandatory weekly groups or individual therapy sessions, and primary health care services. AIDS related services available to all program members include pre- and posttest HIV counseling, confidential HIV test, AIDS risk reduction education, and HIV related health care. This methadone program imposes relatively strict guidelines for program participation and for client continuation in treatment. Compliance with clearly defined program rules is
METHADONE MAINTENANCE TREATMENT AND HIV
37
expected, and repeated infractions result in expulsion from the program. Methadone maintenance doses vary, but average 70 milligrams. During the course of this study, there was a waiting list of approximately 3-4 months for program admission.
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Subjects Individuals who were past or current clients of the methadone maintenance program, were over 18 years of age, and had a personal history of injection drug use were invited to participate in this prospective study of HIV-1 seroconversion if they also met one of the following three criteria: (1) had participated in a 1982-83 study of hepatitis and had an identifiable serum sample from that study in our serum bank; (2) had been in the methadone program consistently since 1982; or (3) entered the methadone program between October, 1985, and July, 1988. Entry into the 1982-83 hepatitis study required mild transaminase elevations without serologic evidence of active hepatitis B infection at the time of that study (1982-83). Seventy seven percent (133/173) of the subjects in the 1982-83 study were located; 54% (56/104) of those who were eligible agreed to participate. The remaining 42 subjects met criteria (2) or (3). Subjects were excluded if they did not wish to be tested for HIV-1 and informed of the test results. Anonymous HIV-1 testing was available throughout the course of the study to all methadone clients, regardless of study participation.
Data collection HIV-1 serum antibody status was determined at enrollment and on follow-up visits. Positive enzyme-linked immunoassays (EIA) were confirmed by immuno-blot (IB) analysis. Reactivity to env and gag or pol proteins were the criteria for positivity. Stored sera specimens were also tested for those subjects who had participated in the earlier (1982-1983) hepatitis study. An interview questionnaire administered on enrollment collected demographic information and self-reported drug use and sexual behaviors. Methadone program treatment histories including duration and dates of treatment, were determined by review of program records. Subjects returned every six months for repeat HIV-1 testing and a brief follow up interview.
Data analysis The association of each variable with HIV-1 serologic status was examined and comparisons of demographic and behavioral variables were made between subjects grouped by treatment history. Univariate analysis was performed using unpaired t-tests for ordinal variables and contingency table analysis using chi-square with continuity correction or Fisher’s exact test for nominal and categorical variables in two by two tables. HIV-1 seroconversion rates per person year were calculated. Odds ratios and 95% confidence intervals were used to provide a measure of association between HIV-1 antibody status and specific variables.
Results Ninety-eight subjects were HIV-1 seronegative at baseline and completed at least one follow-up visit with repeat serologic testing. The follow-up period varied by subject and was defined as the time between study enrollment with a negative HIV-1 EIA and the first IB-
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A. B. WILLIAMS ET AL.
confirmed positive HIV-1 EIA or the final study visit if the subject continued to test negative. For those subjects who had stored sera available from the earlier hepatitis study, the follow-up period began with the date of the initial negative HIV-1 EIA in 1982-83. There were 62 (63%) men and 36 (37%) women. Eighty one (83%) were Caucasian Americans and 17 (1 7%) were African-Americans. There were no Hispanics in this study. The mean age was 35 years [Range (R) = 24-58]. All subjects reported only heterosexual activity. Mean age at first injection drug use was 19 years (R = 12-33). Length of injection drug use was obtained by subtracting age at first injection from current age; the mean length of injection drug use was 16 years (R = 3-38). Forty-seven (48%) reported that they shared drug injection equipment during the study period. Of those who had shared equipment, 36% (17147) had shared with only one person. Two subjects had shared injection equipment with more than 10 individuals. Twelve subjects reported that they used local shooting galleries during the study period; none reported using shooting galleries in New York or New Jersey. During the study period, subjects received a mean of 27 months of methadone maintenance treatment (R = 0-84). We also looked at whether or not subjects had left and then re-entered methadone maintenance treatment during the follow-up time. Fifty-six (57%) of the subjects received one uninterrupted treatment episode during the study period; we called this the Continuous Treatment Group. Forty-two (43%) subjects were not in treatment at all, left treatment, or left and returned to treatment during the study period; they made up the Interrupted Treatment Group.
HIV-1 seroconversion Ninety-eight subjects were followed for a mean of 39 months (R = 7-89). Nine subjects (10%) became IB-confirmed HIV-1 EIA positive during the study period, and 89 remained HIV-1 EIA negative. The seroconversion rate was 2.8 per 100 person years. On univariate analysis, HIV-1 seroconverters did not differ from those who remained HIV- 1 seronegative according to the demographic variables of age, sex, race or employment status. Nor were there significant differences in number of sexual partners during the study period, age at first drug use, length of injection drug use, use of shooting galleries, whether or not needles were shared in the past year, the number of individuals with whom needles were shared, or the total amount of time spent in the methadone program during the study period (Table 1). Subjects who remained on methadone maintenance without interruption during the follow-up period (Continuous Treatment Group) were less likely to seroconvert than those in the Interrupted Treatment Group. One of 56 (2%) subjects in the Continuous Treatment Group seroconverted during the follow-up period. Eight of 42 (19%) subjects in the Interrupted Treatment Group seroconverted [odds ratio (OR) = 12.9, 95% confidence interval (CI) = 1.6 and 584, p = 0.0045, Fisher’s Exact]. Total length of study follow-up differed for the two groups. Subjects in the Continuous Treatment Group were followed for a mean of 29 months (R = 7-84, Median = 17); while subjects in the Interrupted Group were followed for a mean of 53 months (R = 8-89, Median = 57). Therefore, the seroconversion rate per person year was computed for each of the two groups. For the Continuous Treatment Group, the HIV-1 seroconversion rate was 0.7 per 100 person years (95% CI = 0.1 and 5.3). For the Interrupted Treatment Group, the HIV-1 seroconversion rate was 4.3 per 100 person years (95% CI = 2.2 and 8.6). The difference between seroconversion rates for the two groups was not significant (Z = 1.65, p = 0.10, two-sided). Subjects in the Continuous Treatment Group were less likely to have
METHADONE MAINTENANCE TREATMENT AND HIV
39
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Table 1. Demographic and behavioral characteristics of subjects by HIV-1antibody status at conclusion of study n* Variable
HIV-positive
HIV-negative
p-value
98 Mean age 98 Sex Male Female 98 Race Caucasian African-American 85 Employment StaNS Employed Unemployed 95 Number of sexual partners during study 0 1 2-5 6+ 98 Mean age at first injection drug use 98 Mean years of injection drug use 97 Shooting gallery use Used galleries Did not use galleries 97 Needle sharing in past year Shared needles Did not share needles 88 Number of needle sharing partners in past year 0 1 2-5 6 f 98 Mean months of methadone during study period 98 Continuity of methadone treatment Continuous Interrupted
39 years
35 years
0.llt
6 3
56 33
0.894
6 3
75 14
0.39$
2 6
38 39
0.354
6 46 29 5 20 years 16
0.08t
1 8
11 77
0.684
6 3
41 47
0.45$
3 1 3 1 30
47 16 12 5 27
0.34$ 0.67t
1 8
55 34
0.01$
2 5 1 1 19 years 20
0.264 0.72t
* Number of subjects for whom data were available.
t Unpaired t-test, two-tailed.
$ Chi-square with continuity correction.
shared needles in the past year (p = 0.0002, chi-square), reported fewer needle sharing partners (p = 0.002, chi-square) and fewer sexual partners (p = 0.03, chi-square), and were more likely to be women (p = 0.01) (Table 2). Discussion
In this study, subjects in continuous methadone treatment had a non-significant trend toward a lower HIV- 1 seroconversion rate than subjects whose treatment was interrupted. Subjects in continuous treatment were significantly more likely to be women and reported significantly fewer needle sharing and sexual partners than subjects with interrupted treatment. However, HIV- 1 seroconversion was not associated with gender or with reported number of sexual partners or needle sharing partners (Table 1). Therefore, it seems unlikely that the trend seen here toward fewer HIV-1 seroconversions in the continuous treatment group was due to confounding by these factors. However, the small number of subjects as
40
A. B. WILLIAMS ETAL. Table 2. Demographic and behavioral characteristics of subjects by continuity of treatment experience
n* Variable
Continuous
Interrupted
Mean age Sex Male Female 98 Race Caucasian African-American 85 Employment status Emp 1oy ed U nemp 1oy ed 95 Number of sexual partners during study
36 years
35 years
0.60t
29 27
33 9
0.01*
48 8
33 9
0.35$
26 27
14 18
0.80f
4 36 11 3 19 years 16
4 15 19 3 19 years 16
0.03$ 0.71t 0.79t
4 51
8 34
0.154
17 38
30 12
0.0002$
38 9 4
12 8 11 4 42
0.002* 0.55t
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98 98
0 1 2-5 6+
Mean age at first injection drug use Mean years of injection drug use Shooting gallery use Used galleries Did not use galleries 97 Needle sharing in past year Shared needles Did not share needles 88 Number of needle sharing partners in past year 98 98 97
0 1 2-5 6-t 98
*
Mean months of methadone during study period
2 56
p-value
Number of subjects for whom data were available. two-tailed. Chi-square with continuity correction.
t Unpaired t-test,
well as the relatively shorter length of follow up for those in continuous treatment limits the analysis. Larger studies with longer duration of follow up are needed to determine if the suggestion in these data that methadone maintenance treatment lowers HIV- 1 seroconversion risk is true. Such studies should also address the possibility that the same factors which enabled subjects to remain in methadone treatment also enabled them to better protect themselves from HIV- 1 infection. Identification of specific client-associated or programassociated factors affecting both methadone treatment retention and HIV- 1 risk could guide program planners in targeting scarce resources. The data presented here indicate the need for further study and suggest that clients with interrupted treatment histories should be among the priority targets for HIV-1 risk reduction education while we continue the search for more effective treatment for both drug addiction and HIV-1 infection.
Acknowledgements This work was supported by Grant DAO 330-02 from the National Institute on Drug Abuse. We thank the clients and staff of the APT Foundation Methadone Programs for their
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41
participation in this study, Mark Hayes and Martin Waugh for enthusiastic help with data collection, and Dr Peter Bacchetti for statistical consultation.
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