Table 1.
Characteristics of included studies of opiate substitution treatment (OST) and impact on HIV transmission
| Study | Follow-up | Study type | Recruitment site/method | Inclusion criteria | Sample size* | HIV incidence (95% CI)† | Intervention | Impact of treatment on HIV seroconversion | Confounders included in adjusted analyses | |
|---|---|---|---|---|---|---|---|---|---|---|
| Effect measure | Effect estimate (95% CI) | |||||||||
| Studies included in meta-analysis | ||||||||||
| Bruneau, 2012 (unpublished)‡ Montreal Canada | 1992-2008 | Cohort | Street, word of mouth, community programmes | Age >18; injected for past 6 months | 1374 | 2.57 (2.0 to 3.2) | MMT in previous 6 months (yes/no) | HR | 0.2 (0.0 to 0.7), adjusted 0.3 (0.1 to 1.3) | Age, sex, housing, cocaine use, heroin use, sharing, booting, having sex with person known to be HIV positive, period of recruitment |
| Chitwood, 1995, Miami, US39 | 1988-91 | Nested case-control | Drug treatment programme; street | Cases: participants testing positive for HIV infection 1988-1991. Control: participants testing negative for HIV infection within 2 week period before date of first positive test of case | 97 | 2.1 | Methadone treatment in year before seroconversion or last negative test date (yes/no) | OR | 0.3 (0.1 to 0.9), adjusted 0.7 (0.2 to 2.8) | Age, sex, ethnicity |
| Deren, 2012 (unpublished), Bayamon, Puerto Rico | 1998-2002 | Cohort | Targeted sampling based on ethnographic mapping | Age ≥18, injected drugs in previous 30 days, use of heroin in previous 48 hours, self identification as Puerto Rican | 143 | 3.7 (2.3 to 6.1) | MMT at baseline (yes/no) | IRR | 0.2 (0.0 to 3.5) | |
| Deren, 2012 (unpublished), New York City, US | As above | As above | As above | 154 | 0.83 (0.3 to 2.2) | MMT at baseline (yes/no) | IRR | 0.3 (0.0 to 2.4) | ||
| Judd, 2012 (unpublished), London, UK | 2001-02 | Cohort | Community, such as needle and syringe exchange programmes or street settings | Age <30; injecting ≤6 years; injected previous 4 weeks; address for follow-up | 272 | 2.9 | OST for ≥6 months in last year (yes/no) | IRR | 0.8 (0.2 to 3.2), adjusted 0.8 (0.2 to 3.2) | Crack injection, homelessness |
| Kerr, 2006, Vancouver, Canada37 | 1996-2002 | Cohort | Street outreach; self referral | Injected drugs in past month; resident in Vancouver region | 1013 | 3.2 (2.6 to 3.7) | Methadone treatment in previous 6 months (yes/no) | RH | 0.7 (0.4 to 1.1), adjusted 0.8 (0.5 to 1.4) | Sex, aboriginal ethnicity, frequent cocaine injection, frequent heroin injection, requiring help injecting, binge drug use, having HIV positive sexual partner‡ |
| Metzger, 1993, Philadelphia44 | 1989-91 | Cohort | Outpatient methadone programme; community outreach | MMT: methadone programme participation; no MMT: >18 years; history of intravenous opiate use (≥3/week); no drug treatment in previous 10 months | 185 | 3.0 in treatment; 10.7 out of treatment | MMT over 18 month period (yes/no) | OR | 0.1 (0.0 to 0.5), adjusted 0.2 (0.1 to 0.6) | Age, sex, ethnicity, needle sharing |
| Nelson, 2002, Baltimore, US8 | 1988-98 | Cohort | Community outreach | Αge ≥18; free from AIDS at baseline; injected drugs in past 10 years | 1846 | 3.1 (2.8 to 3.5) | MMT in previous 6 mo (yes/no) | IRR | 0.6 (0.3 to 0.9) | |
| Suntharasamai, 2009, Bangkok, Thailand17 | 1999-2003 | Nested cohort in RCT | Drug treatment clinics and community | HIV negative; history of injected drug use in previous year; age 20-60; informed consent | 2546 | 3.4 (3.0 to 3.9) | MMT in previous 6 months (yes/no) | HR | 0.8 (0.6 to 1.0), adjusted 0.60 (0.4 to 0.8) | Incarceration, injecting drugs, injecting daily, sharing injecting equipment, participation in methadone detoxification programme§ |
| Van den Berg, 2007 Amsterdam, Netherlands45 | 1985-2005 | Cohort | Drug treatment clinics and self referral | History of ever injecting drugs; negative for HIV and/or HCV negative at study entry or at start of injecting drug use | 710 | 1.65 | Any dose of MMT daily in previous 6mo (yes/no) | IRR | 0.4 (0.2 to 0.5) | |
| Vanichseni, 2001, Bangkok, Thailand11 | 1995-98 | Cohort | Drug treatment clinic | History of injected drug use; age 18-50; attendance at Bangkok Metropolitan Administration drug treatment clinics; not known to be HIV seropositive | 1124 | 5.8 (4.8 to 6.8) | MMT or detoxification in previous 4 months (yes/no) | IRR | 0.8 (0.5 to 1.3) | |
| Williams, 1992, New Haven, US46 | 1992-98 | Cohort | Methadone maintenance programme | History of injected drug use; past/current client of MMT programme; age ≥18 and one of three additional criteria** | 98 | 2.8 | Continuous MMT v interrupted MMT during follow-up | IRR | 0.2 (0.0 to 1.3) | |
| Studies not included in meta-analysis | ||||||||||
| Moss, 1994 San Francisco, US43 | 1985-90 | Cohort | Methadone maintenance/ detoxification programmes; hospital | HIV negative heterosexual people who inject drugs tested at least twice | 681 | 1.9 | ≤12 lifetime months in MMT (yes/no) | HR | 5.1, adjusted 4.0 | Age, sex, ethnicity |
| Ruan, 2007, Xichang City, China38 | 2002-05 | Cohort | Community outreach and peer referral | HIV seronegative; age ≥18; injected of drugs in previous 3 months; willing to provide informed consent | 229 | 2.3 (1.1 to 3.5) | MMT in previous 6 months (yes/no) | — | MMT: 0 sc No MMT: incidence 2.9/100 person years | |
| Serpelloni, 1994, Verona, Italy48 | 1985-91 | Nested case-control | Drug dependency unit | HIV seronegative injecting drug users | 80 | — | No of cycles of MMT; daily dose; time out of treatment (previous 12 months) | — | See footnote†† | |
| Zangerle, 1992, Innsbruck, Austria47 | 1985-90 | Cohort | Drug dependency or AIDS clinic | Injecting drug users attending drug dependency or AIDS clinic of University of Innsbruck | 102 | 5.8 | MMT for ≥2 months duration (yes/no) | — | MMT: 0/43 sc over mean 1.6 year; No MMT: 10/59 sc over mean 1.76 years (incidence 9.6/100 person years) | |
sc=seroconversions; MMT=methadone maintenance treatment; IRR=incidence rate ratio; RH=relative hazard; HR=hazard ratio; OR=odds ratio.
*Size of sample of HIV negative participants in analysis of impact of opiate substitution treatment on HIV incidence.
†As rate per 100 person years. Incidence relates to entire study period when such an estimate was provided in study.
‡Effect estimate adjusted for all variables significantly associated with time to HIV infection in univariate analyses at P≤0.1, as listed. Variables refer to preceding 6 months
§Effect estimate adjusted for all variables significantly associated with incident HIV infection at P≤0.1 in bivariate analysis, as listed.Variables refer to preceding 6 months.
¶Study participants with “no dependence” were excluded from analysis to calculate this estimate from reported data.
**Additional criteria for study entry included: had participated in 1982-83 study of hepatitis and had identifiable serum sample from that study in serum bank of researchers; had been in methadone programme consistently since 1982; or entered methadone programme between October 1985, and July 1988. Entry into 1982-83 hepatitis study required mild increases in transaminase activity without serological evidence of active hepatitis B infection at time of study (1982-83).
††Lower dose and more time out of treatment associated with increased risk of HIV infection in univariate but not multivariate analyses. Number of cycles of MMT not significantly associated with risk of HIV infection.