BRIEF REPORT: Methadone Treatment of Injecting Opioid Users for
Prevention of HIV Infection
Linda R. Gowing, PhD,1Michael Farrell, MRCP, MRCPsych2
Reinhard Bornemann, MD, DrPH, PhD3Lynn E. Sullivan, MD4
Robert L. Ali, MBBS, FAFPHM, FAChAM, GDPH1
1University of Adelaide and Drug and Alcohol Services, South Australia, Australia;2National Addiction Centre, UK;
3Universitaet Bielefeld, Bielefeld, Germany;4Yale University School of Medicine, New Haven, CT, USA.
OBJECTIVE: To assess the effects of oral substitution treatment for op-
ioid-dependent injecting drug users on HIVrisk behaviors and infections.
DATA SOURCES: Multiple electronic databases were searched. Refer-
ence lists of retrieved articles were checked.
METHODS: Because of varying methodologies of available studies, this
systematic review was limited to a descriptive summary, looking at
consistency of outcomes across studies.
RESULTS: Twenty-eight studies involving methadone treatment were
included in the review. Methadone maintenance treatment is associat-
ed with statistically significant reductions in injecting use and sharing
of injecting equipment. It is also associated with reductions in numbers
of injecting drug users reporting multiple sex partners or exchanges of
sex for drugs or money, but has little effect on condom use. It appears
that the reductions in risk behaviors do translate into fewer cases of
CONCLUSIONS: Methadone maintenance treatment for injecting drug
users significantly reduces the risk of transmission of HIV and should
be provided as a component of a strategic approach to the prevention
and control of HIV infection. There is insufficient evidence to determine
whether other forms of oral substitution treatment also reduce the risk
of HIV transmission.
KEY WORDS: HIV infections: prevention and control; substance abuse,
intravenous: drug therapy; opioid-related disorders: drug therapy;
methadone: therapeutic use.
J GEN INTERN MED 2006; 21:193–195.
detail of the methods and results.
The goal of this review was to assess the effectiveness of
oral substitution treatment for opioid-dependent injecting
drug users (IDU) in preventing the spread of HIV.
In the United States, 22% of AIDS cases diagnosed in
2003 were attributed to injection drug use.2
his paper presents the main findings of a systematic (Co-
chrane) review. The full review1should be consulted for
Multiple electronic databases were searched from their date of
commencement (the latest was 1985) to July 2003 using a
strategy addressing opioid dependence, HIV transmission and
methadone, and other substitution treatment agents.
Eligible studies included opioid-dependent injecting drug
users; involved the oral administration of opioid agonists for
substitution treatment; and considered behaviors with a high
risk for HIV transmission, or the incidence of HIV infection.
The data from the studies varied in a number of aspects, in-
cluding the interval between baseline and follow-up inter-
views; the proportion of participants injecting at baseline; the
reporting period for assessment of HIV risk behaviors; and the
means of reporting frequency data. This variability reduced the
validity of any calculated combined effect. Consequently, this
review was limited to a descriptive summary of studies of var-
ying methodologies, which considers the consistency in out-
comes reported by the individual studies without metaanalysis
to quantify overall effect size.
Primary outcome measures were behaviors with a high
risk of transmission of HIV, including injecting drug use, shar-
ing of injecting equipment, unprotected sex, multiple sexual
partners, and providing sex in exchange for money or drugs.
The incidence of HIV was also assessed.
Description of Included Studies
Twenty-eight studies involving 7,900 participants were includ-
ed in the review. In all 28 studies, methadone was used for
substitution treatment. Only 2 studies3,4were randomized
controlled trials of oral substitution treatment.
The studies reported 4 types of data: HIV risk behavior at
baseline prior to treatment entry, and at follow-up, after a pe-
riod of methadone treatment (18 studies); HIVrisk behavior for
participants receiving methadone treatment at the time of as-
sessment compared with participants receiving no or limited
methadone treatment (4 studies); HIV risk behaviour in co-
horts of drug users either continuing in or ceasing methadone
treatment (3 studies); and exposure to methadone treatment
for cohorts who HIV seroconverted or remained HIV seroneg-
ative over a defined period (4 studies).
Manuscript received February 16, 2005
Initial editorial decision April 12, 2005
Final acceptance September 2, 2005
The authors have no conflicts of interest to report.
Address correspondence and requests for reprints to Dr. Gowing: Ev-
idence-Based Practice Unit, Drug and Alcohol Services, South Australia,
161 Greenhill Road, Parkside SA 5063, Australia (e-mail: linda.gowing@
Effect of Methadone Treatment on
All 6 studies3,5–9that reported data on the proportion of par-
ticipants reporting injecting use before and after a period of
methadone treatment show a significant decrease in injecting
from baseline to follow-up.
Similarly 8 studies3,5,6,10–14that reported data on the fre-
quency of injecting use all show a significant decrease from
baseline to follow-up.
Four studies12,15,16that provided data on injecting use for
cohorts of drug users receiving or not receiving methadone
treatment at the time of a single interview indicate significantly
less injecting use for participants in methadone treatment.
All 7 studies3,5–8,17,18that reported data on the proportion
of participants sharing injecting equipment, before and after a
period of methadone treatment showed a reduction. The dif-
ference was significant for 6 of the 7 studies. The remaining
study8reported a nonsignificant reduction (risk ratio [RR]
0.54, 95% confidence interval [CI] 0.23, 1.27).
Four studies provided data on sharing of injecting equip-
ment for participants engaged in methadone treatment com-
pared with those receiving no or limited methadone treatment.
In 3 studies3,16,19those receiving methadone treatment were
significantly less likely to report sharing. In the fourth study,20
fewer participants in methadone treatment reported sharing
injecting equipment, but the difference did not achieve statis-
tical significance (RR 0.79, 95% CI 0.53, 1.19).
Three6,21,22of 4 studies that reported rating scale scores
of drug-related HIV risk behavior before and after a period of
methadone treatment found significant decreases. In the
fourth study4there was a nonsignificant reduction in the mean
score between intake and 6-month follow-up.
Another study23reported significantly lower drug risk
scores for a cohort of IDU in methadone maintenance with co-
horts not in treatment at the time of assessment.
Effect of Methadone Treatment on
In 35,6,17of 4 studies that reported data on the proportion of
participants reporting multiple sex partners or exchanges of
sex for drugs or money, significantly fewer participants report-
ed these behaviors following methadone treatment, compared
with baseline. Relatively few participants in the fourth study8
reported these behaviors either before (5 of 69) or after (7 of 69)
Two studies provided data on exchange of sex for drugs or
money for cohorts of drug users receiving or not receiving
methadone treatment at the time of interview. One study16
found that significantly fewer of the cohort in methadone treat-
ment reported exchanges; the other study15reported a signif-
icantly lower frequency of exchanges for the cohort in
Data on exposure to unprotected sex was reported in dif-
ferent ways. A statistic that could be extracted from most stud-
ies was the use of condoms on half or less of occasions. Hence
this was used as the definition of exposure to unprotected sex.
Four5–7,18of 6 studies reported statistically significant re-
ductions. Of the 2 studies with nonsignificant reductions, 117
found that fewer participants reported unprotected sex at fol-
low-up, and in the other8most participants reported unpro-
tected sex (84% at baseline, 88% at follow-up).
Two studies16,19comparing cohorts of IDU in or out of
methadone treatment found no significant difference in con-
dom use. A third study15reported a higher frequency of con-
dom use in the 30 days prior to interview for a cohort not in
methadone treatment, compared with those currently in meth-
adone treatment (standardized mean difference ?0.28, 95%
CI ?0.55, 0.00).
Two studies21,22reported scores of sex-related risk from
scales of HIV risk behaviors found a significant reduction in
the score from baseline to follow-up after 6 months of substi-
tution treatment. A third study4reported a nonstatistically
One study23found no difference in sex-related risk scores
for IDU currently in methadone maintenance treatment, com-
pared with those previously in, or with no prior history of
Effect of Methadone Treatment on Seroconversion
Metzger et al.16found that over a period of 18 months, the odds
of seroconversion among an untreated group, compared with a
group in methadone treatment, were 7.63 (CI 1.99, 29.27,
Moss et al.24reported that 11 of 145 (7.6%) with less than
12 lifetime months in methadone maintenance seroconverted,
compared with 11 of 536 (2.1%) with 12 or more lifetime
months of methadone maintenance (P=.002).
Williams et al.25reported a seroconversion rate of 0.7 per
100 person years for those in continuous methadone treat-
ment (mean 29 months), compared with 4.3 per 100 person
years for those with interrupted treatment (over a mean 53
Serpelloni et al.26found that the risk of HIV infection in-
creased 1.5 times for every 3 months out of methadone treat-
ment in the 12 months prior to seroconversion.
The studies identified in this review, whether controlled trials
or other types of study, provide evidence that methadone treat-
ment in opioid-dependent IDU is associated with significant
reductions in HIV risk behaviors as well as rates of HIV sero-
The studies consistently revealed a decrease in the pro-
portion of participants reporting injecting use, the frequency of
injection, the sharing of injecting equipment, and drug-related
HIV risk scores.
The data suggest that methadone treatment is associated
with a lower likelihood of multiple sex partners or exchanges of
sex for drugs or money but no change, or only small decreases,
in unprotected sex. This indicates an effect on behaviors that
are probably directly related to obtaining drugs, but not on
behaviors that are influenced by other factors, such as capac-
ity and willingness to negotiate the use of condoms.
Importantly, the studies of seroconversion rates are con-
sistent in indicating lower rates of seroconversion associated
with methadone treatment. This suggests that reductions in
risk behavior do translate into actual reductions in cases of
Gowing et al., Methadone Treatment for Prevention of HIV
It is unclear to what extent continued injecting behavior Download full-text
during methadone treatment is related to the use of nonopioid
drugs. Assessing the extent of reduction of HIV risk behavior
associated with methadone treatment of injecting opioid users
will require further knowledge of the drugs being injected by
those who continue injecting after entry into methadone treat-
One recent study27reported a significant reduction in HIV
risk associated with buprenorphine maintenance treatment,
but in the absence of other studies, it is currently not possible
to compare methadone with other forms of substitution treat-
ment in terms of capacity to reduce HIV risk behavior. Simi-
larly, different types of psychosocial interventions should be
compared with methadone treatment on capacity to reduce
HIV risk behavior.
Most controlled trials comparing methadone with other
substitution pharmacotherapies rely on urine screening and
retention in treatment as primary outcome measures. Includ-
ing an assessment of HIV risk behavior as an outcome meas-
ure in controlled trials would add a further important
dimension to the assessment of effectiveness of substitution
The studies identified in this review add to the strong ev-
idence of effectiveness of methadone treatment on drug use,
and treatment retention outcomes shown by other systematic
reviews while providing important data on the efficacy of meth-
adone treatment in decreasing HIV risk behaviors.28,29The
provision of methadone treatment for injecting drug users sig-
nificantly reduces the risk of transmission of HIV and should
be provided as a component of a strategic approach to the pre-
vention and control of HIV infection.
Sources of support: Drug and Alcohol Services South Australia;
National Addiction Centre, UK; University of Adelaide, SA.
1. Gowing L, Farrell M, Bornemann R, Ali R. Substitution treatment of
injecting opioid users for prevention of HIV infection [Cochrane Review].
In: The Cochrane Library, Issue 4. Chichester, UK: John Wiley & Sons;
2. Centre for Disease Control and Prevention. HIV/AIDS Surveillance
Report, 2003. Atlanta: U.S. Department of Health and Human Services,
2004. Available from: http://www.cdc.gov/hiv/stats/hasrlink.htm
3. Dolan KA, Shearer J, MacDonald M, Mattick RP, Hall W, Wodak AD. A
randomised controlled trial of methadone maintenance treatment versus
wait list control in an Australian prison system. Drug Alcohol Depend.
4. Sees KL, Delucchi KL, Masson C, et al. Methadone maintenance vs
180-day psychosocially enriched detoxification for treatment of opioid
dependence: a randomized controlled trial. JAMA. 2000;283:1303–10.
5. Camacho LM, Bartholomew NG, Joe GW, Cloud MA, Simpson DD.
Gender, cocaine and during-treatment HIV risk reduction among injec-
tion opioid users in methadone maintenance. Drug Alcohol Depend.
6. Chatham LR, Hiller ML, Rowan-Szal GA, Joe GW, Simpson DD. Gen-
der differences at admission and follow-up in a sample of methadone
maintenance clients. Subst Use Misuse. 1999;34:1137–65.
7. Gossop M, Marsden J, Stewart D, Rolfe A. Patterns of improvement af-
ter methadone treatment: 1 year follow-up results from the National
Treatment Outcome Research Study (NTORS). Drug Alcohol Depend.
8. King VL, Kidorf MS, Stoller KB, Brooner RK. Influence of psychiatric
comorbidity on HIV risk behaviors: changes during drug abuse treat-
ment. J Addict Dis. 2000;19:65–83.
9. Magura S, Siddiqi Q, Freeman RC, Lipton DS. Changes in cocaine use
after entry to methadone treatment. J Addict Dis. 1991;10:31–45.
10. Batki SL, Sorensen JL, Gibson DR, Maude-Griffin P. HIV-infected i.v.
drug users in methadone treatment: outcome and psychological corre-
lates—a preliminary report. NIDA Res Monogr. 1989;95:405–6.
11. Brooner R, Kidorf M, King V, Beilenson P, Svikis D, Vlahov D. Drug
abuse treatment success among needle exchange participants. Public
Health Rep. 1998;113:129–39.
12. Kwiatkowski CF, Booth RE. Methadone maintenance as HIV risk re-
duction with street-recruited injecting drug users. J Acquir Immune De-
fic Syndr. 2001;26:483–9.
13. Simpson DD, Joe GW, Rowan-Szal G, Greener J. Client engagement
and change during drug abuse treatment. J Subst Abuse. 1995;7:117–
14. Strang J, Marsden J, Cummins M, et al. Randomized trial of supervised
injectable versus oral methadone maintenance: report of feasibility and
6-month outcome. Addiction. 2000;95:1631–45.
15. Meandzija B, O’Connor PG, Fitzgerald B, Rounsaville BJ, Kosten TR.
HIV infection and cocaine use in methadone maintained and untreated
intravenous drug users. Drug Alcohol Depend. 1994;36:109–13.
16. Metzger DS, Woody GE, McLellan AT, et al. Human immunodeficiency
virus seroconversion among intravenous drug users in- and out-of-treat-
ment: an 18-month prospective follow-up. J Acquir Immune Defic Syndr.
17. Grella CE, Anglin D, Rawson R, Crowley R, Hasson A. What happens
when a demonstration project ends. Consequences for a clinic and its
clients. J Subst Abuse Treat. 1996;13:249–56.
18. Margolin A, Avants SK, Warburton LA, Hawkins KA, Shi J. A
randomized clinical trial of a manual-guided risk reduction inter-
vention for HIV-positive injection drug users. Health Psychol. 2003;22:
19. Stark K, Muller R, Bienzle U, Guggenmoos-Holzmann I. Methadone
injecting drug users in Berlin. J Epidemiol Community Health. 1996;50:
20. Thiede H, Hagan H, Murrill CS. Methadone treatment and HIV and
hepatitis B and C risk reduction among injectors in the Seattle area. J
Urban Health. 2000;77:331–45.
21. Abbott PJ, Weller SB, Delaney HD, Moore BA. Community reinforce-
ment approach in the treatment of opiate addicts. Am J Drug Alcohol
22. Avants SK, Margolin A, Sindelar JL, et al. Day treatment versus en-
hanced standard methadone services for opioid-dependent patients: a
comparison of clinical efficacy and cost. Am J Psychiatry. 1999;156:27–
23. Baker A, Kochan N, Dixon J, Wodak A, Heather N. HIV risk-taking be-
haviour among injecting drug users currently, previously and never en-
rolled in methadone treatment. Addiction. 1995;90:545–54.
24. Moss AR, Vranizan K, Gorter R, Bacchetti P, Watters J, Osmond D.
HIV seroconversion in intravenous drug users in San Francisco, 1985–
1990. AIDS. 1994;8:223–31.
25. Williams AB, McNelly EA, Williams AE, D’Aquila RT. Methadone main-
tenance treatment and HIV type 1 seroconversion among injecting drug
users. AIDS Care. 1992;4:35–41.
26. Serpelloni G, Carrieri MP, Rezza G, Morganti S, Gomma M, Binkin N.
Methadone treatment as a determinant of HIV risk reduction among in-
jecting drug users: a nested case-control study. AIDS Care. 1994;6:215–
27. Marsch LA, Bickel WK, Badger GJ, Jacobs EA. Buprenorphine treat-
ment for opioid dependence: the relative efficacy of daily, twice and thrice
weekly dosing. Drug Alcohol Depend. 2005;77:195–204.
28. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance
therapy versus no opioid replacement therapy for opioid dependence.
Cochrane Library; 2002.
29. Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance
versus placebo or methadone maintenance for opioid dependence. Co-
chrane Database Syst Rev. 2003;CD002207.
Gowing et al., Methadone Treatment for Prevention of HIV