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AIDS Patient Care and STDs
AIDS Patient Care STDS. 2012 January; 26(1): 36–52.
PMCID: PMC3248609

A Systematic Review of Behavioral and Treatment Outcome Studies Among HIV-Infected Men Who Have Sex with Men Who Abuse Crystal Methamphetamine

Radha Rajasingham, M.D.,corresponding author1 Matthew J. Mimiaga, Sc.D., M.P.H.,2,,3,,5 Jaclyn M. White, M.P.H.,5 Megan M. Pinkston, M.A., Ph.D.,4 Rachel P. Baden, M.D.,1 and Jennifer A. Mitty, M.D., M.P.H.1


Men who have sex with men (MSM) have the highest incidence of HIV infection in the United States. One of the contributing factors to HIV spread among this group is the use of crystal methamphetamine (“meth”). The objective was to review the behavioral impact of crystal meth use in HIV-infected MSM and potential treatment options. A systematic review of MEDLINE identified studies that evaluated the clinical effects of crystal meth on the HIV-infected MSM population. Search terms included HIV, methamphetamine, MSM, antiretroviral therapy, adherence, resistance, and treatment. U.S. citations in the English language in peer-reviewed journals until December 2010 were included. The primary author reviewed eligible articles, and relevant data including study design, sample, and outcomes were entered into an electronic data table. The 61 included studies highlight that HIV-infected MSM who use crystal meth are more likely to report high-risk sexual behaviors, incident sexually transmitted infections, and serodiscordant unprotected anal intercourse, compared to HIV-infected MSM who do not use crystal meth. Medication adherence in this population is notably low, which may contribute to transmission of resistant virus. No medications have proven effective in the treatment of crystal meth addiction, and the role of behavioral therapies, such as contingency management are still in question. HIV-infected MSM who abuse crystal meth have worse HIV-related health outcomes. Behavioral interventions have shown variable results in treating crystal meth addiction, and more investigation into rehabilitation options are needed. The results presented support efforts to develop and implement novel interventions to reduce crystal meth use in HIV-infected MSM.


Fifty-three percent of new HIV infections in the United States in 2006 were among men who have sex with men (MSM).1 The incidence of HIV has been climbing in this population since the 1990s, and MSM continue to bear a disproportionate burden of new HIV infections. Unprotected anal sex is a significant risk factor for HIV transmission and acquisition in this group of men, and is closely associated with substance use, particularly crystal methamphetamine (“meth”) use.2 In fact, the incidence of HIV in MSM who use crystal meth is more than double that of MSM who do not use crystal meth3 and a relationship between increased intensity of crystal meth use and HIV risk has been observed.4 While previous reviews have highlighted the growing problem of crystal meth use in HIV-uninfected MSM, the data on clinical outcomes and potential therapies among those who are infected with HIV are just emerging. HIV-infected MSM who use crystal meth can experience a broad range of destructive outcomes including failure to adhere to medications, decreased access to medical care, and increased sexual risk behavior.515 Being diagnosed with HIV may have an impact on motivations surrounding crystal meth use, and success with treatment, compared to the HIV-uninfected population. In this review, we systematically examine crystal meth use in HIV-infected MSM with a specific focus on HIV-related behavioral health outcomes and potential treatment options.


Data sources and searches

We conducted a systematic search of MEDLINE using combinations of the keywords HIV, methamphetamine, MSM, antiretroviral therapy, adherence, resistance, and treatment to identify studies that evaluated the clinical effects of crystal meth on the HIV-infected MSM population. Our search was limited to English-language, human, original research published in peer-reviewed journals until December 2010. Only U.S. citations were included as the limited literature from Western Europe and Australia only points toward the association of crystal meth with high-risk behavior, without particular attention to HIV-related outcomes in MSM. The bibliographies from included articles were manually reviewed for additional relevant studies.

Study selection

Our search yielded 376 citations, which were screened at the abstract level for relevance to the HIV-infected, MSM population using crystal meth. Twenty-four additional articles were obtained from the manual review of bibliographies. Included were qualitative and quantitative studies reporting original data on sexual risk behaviors, medication adherence, and treatment outcomes of HIV-infected MSM who use crystal meth. We excluded abstracts that were not original research in a peer-reviewed journal or did not study the HIV-infected MSM population in the United States. As this is a review of the behavioral and treatment outcomes, basic science literature was excluded. A total of 100 abstracts were eligible for full article review and an additional 39 were excluded based on the above criteria. Full articles were reviewed to ascertain whether or not they were applicable to the HIV-infected, MSM, crystal meth-using population. Notably, there were a small number of publications that addressed stimulant use, where data from crystal meth use were combined with cocaine use. These articles addressing stimulant use were included to broaden the number of studies available for review. When a study combined stimulants, this was noted in the text. There were also a small number of articles that were not exclusively focused on HIV-infected MSM. These were included because the studies revealed information about HIV seroconversion or patterns of behavior that may be relevant to HIV-infected MSM. Furthermore, articles were included that cited treatment options for crystal meth-dependence in non-MSM or HIV-uninfected persons, as only one study exclusively examined the population of interest, and research among mixed samples may be applicable to this group. Ultimately, 61 articles met our eligibility criteria (Fig. 1). Thirty-nine studies describe sexual risk behavior, 6 relate to antiretroviral therapy adherence and/or drug resistance, and 16 pertain to treatment options. The primary author reviewed eligible articles, and relevant data including study design, sample, and outcomes were entered into an electronic data table. Given the early stage of research in this field, all studies were included regardless of methodological rigor. Methodological limitations are reported in the text where relevant.

FIG. 1.
Summary of study selection.

Data synthesis

Results of the studies were synthesized qualitatively. Studies were grouped into 1 of 3 topics in electronic tables. Review topics include: sexual risk behavior, antiretroviral therapy adherence and/or drug resistance, and crystal meth treatment options. We also examined sexually transmitted infections (STI) and reasons for crystal meth use in HIV-infected MSM. Quantitative results were presented from each study, with specified odds ratios and 95% confidence intervals where available.


HIV risk behavior

HIV-infected MSM who use crystal meth are more likely to engage in unprotected anal intercourse (UAI),5,8,16,17 have group sex,18 have multiple sex partners,5,8,10,19 find sexual partners on the Internet,8 have sex with an injection drug user,5 and be high or intoxicated during sex5,8 compared to MSM who do not use crystal meth, regardless of HIV status (Table 1). Furthermore, qualitative research of HIV-infected, crystal meth-using MSM indicates that crystal meth use is associated with high rates of anal sex, low rates of condom use, sexual marathons (i.e., sexual activities lasting hours or days with one or more partner), and sex with anonymous partners.14 Another qualitative study of 27 HIV-infected MSM observed that UAI was related to substance use in general (8% used crystal meth), social environmental factors such as high-risk venues, engaging in sex work, and psychological factors such as increase in sexual drive, lack of inhibition, and a decrease in the desire for sexual intimacy.20 Characteristics of one's sexual partner and unspoken beliefs about the partner's HIV status also had a role in determining whether to engage in high-risk sexual behaviors.

Table 1.
Summary of Sexual Risk Behavior Associated with HIV-Infected, Meth-Dependent MSM

Compared to other drugs of abuse, crystal meth is a particularly strong predictor of UAI in this population.6,21 Moreover, among HIV-infected MSM with a serodiscordant (HIV-uninfected or unknown HIV status) sexual partner, crystal meth use is significantly associated with UAI (insertive: odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.3; receptive: OR 1.6, 95% CI 0.9–3.1).22 This has been corroborated by multiple studies.2325 There are subgroups within this community with variable patterns of crystal meth use that engage in behaviors that are at particularly high risk for HIV transmission and STI acquisition. These include crystal meth users who use sildenafil (Viagra®, Pfizer Inc., New York, NY)6,21,2527 or other illicit drugs during sex,28,29 those who trade crystal meth for sex,15 those who report high levels of sexual compulsivity,25,30 those who engage in sexual encounters in public venues,31,32 and those who report crystal meth binges.33 Additionally, crystal meth use in MSM has been associated with a recent diagnosis of HIV infection (OR 3.02, 95% CI 2.30–3.99),34 suggesting that new HIV infection may be the result of engaging in high-risk behaviors while under the influence of crystal meth.3,6,18,3544 A case-control study comparing 32 HIV-infected MSM cases to 110 HIV-uninfected MSM controls observed that crystal meth use during UAI was independently associated with recent HIV infection (adjusted odds ratio [aOR]=9.0, 95% CI 1.5–55.0).43 Another study found that of 20 HIV-infected, crystal meth-using MSM, 50% did not consistently disclose their HIV status to sexual partners.11 Together these findings highlight the strong association between crystal meth use, HIV risk behavior, and subsequent HIV infection.

Sexually transmitted infections

Given the increased frequency of high-risk sexual behavior associated with crystal meth use, it is not surprising that both HIV-infected and uninfected MSM who use crystal meth have a greater risk of STIs compared to MSM who do not use crystal meth.8,34 Studies have shown that HIV-infected MSM who use crystal meth are more likely to report a history of STI,6,41 specifically gonorrhea (59.5% versus 26.9%, p<0.01), compared to HIV-uninfected MSM who use crystal meth.45 Furthermore, HIV-infected MSM who have used crystal meth in the prior 3 months have a significantly higher odds of being diagnosed with an STI (gonorrhea, chlamydia, or syphilis) in the past year, compared to HIV-infected MSM who have not used crystal meth (OR=3.37, 95% CI 1.67–6.81).16

With regard to STIs, another area of public health concern is the combination of crystal meth with sildenafil during sex. The use of sildenafil in MSM irrespective of substance use has been associated with higher rates of UAI.46 With respect to crystal meth specifically, often crystal meth abusers use sildenafil to counteract the side effect of erectile dysfunction, a frequent side effect of stimulant use. One survey of 1318 MSM (both HIV-infected and uninfected) showed that risk factors for early syphilis included use of both crystal meth and sildenafil together (OR=6.2, 95% CI 2.6–14.9) and crystal meth use alone (OR=3.2, 95% CI 1.3–7.6), compared to MSM who had not used either drug.26 Another cross-sectional study of 1976 MSM found that of those who used crystal meth with sildenafil, 57% were HIV infected.22 Additionally, this group was significantly more likely to engage in serodiscordant UAI (OR=4.0, 95% CI 2.2–7.5) and be diagnosed with an STI (OR=3.0, 95% CI 1.6–5.5) compared to those who had not used crystal meth and sildenafil in the last year.

Reasons for crystal meth use

HIV-infected MSM are more likely to report crystal meth use compared to HIV-uninfected MSM.8,23,32 In a study of 340 HIV-infected crystal meth-using MSM participants were asked to cite the reasons why they used crystal meth. Explanations included to experiment, to party, to enhance sexual pleasure, to get more energy, to escape, to meet sex partners, to feel more self-confident, to deal with grief, to feel more attractive, and to cope with HIV-related symptoms.47 Another study of 48 crystal meth-using MSM (56% HIV infected) found that HIV-infected MSM were more likely to use crystal meth for sexual reasons compared to HIV-uninfected MSM (85.2% versus 50%, p=0.009).48 Participants described the sexual enhancement while using crystal meth as prolonging sexual encounters and enhancing sexual feelings and attitudes toward sex. Another study found that HIV-infected MSM not only used crystal meth for sexual reasons, but also to cope with their HIV diagnosis, either by making them feel more physically energetic, helping them to view their situation in a more positive light, or by providing an escape from social rejection and depression.14

HIV medication adherence

Prior studies have clearly shown that active substance abuse is associated with significantly decreased medication adherence, higher viral loads, opportunistic infections, and increased mortality in HIV-infected persons.4952 However, these studies were primarily conducted in heterosexual users of cocaine, crack, or opiates. The literature specifically investigating medication adherence in HIV-infected MSM who use crystal meth is limited (Table 2). One cross-sectional study of HIV-infected patients (39% MSM) showed that crystal meth use in the prior 4 weeks was associated with poor antiretroviral therapy (ART) adherence (27% versus 13%, 95% CI: 1.3–3.5, p<0.05).10 Additionally, crystal meth users were less likely to be on ART than non-crystal meth users (57.5% versus 70%, 95% CI 0.6–0.9, p<0.02). In a prospective cohort of highly active antiretroviral therapy (HAART) adherence, 102-HIV-infected drug users (i.e., tested positive for opioids, crystal meth, benzoylecgonine, tetrahydrocannabinol, phencyclidine, and/or barbiturates) were compared to 48 HIV-infected drug-free participants.53 Investigators used medication event monitoring system (MEMS) caps to assess medication adherence. Poor adherence was defined as taking less than 90% of prescribed doses of HAART. Notably, more than half (65%) of the study population identified as MSM and 70% of drug-positive participants were stimulant users (27% tested positive for cocaine only; 70% tested positive for cocaine and crystal meth; and 3% tested positive for crystal meth only). The study observed that HAART adherence was poorest among active stimulant users compared to users of other drugs (p=0.001). Moreover, active stimulant users were 7 times more likely to have poor adherence compared to drug-free participants (OR 7.0, 95% CI 1.8–9.3, p<0.01). While the study did not include analyses for crystal meth users alone, researchers found that those who used crystal meth and cocaine together had a trend toward poorer adherence compared to those who used cocaine alone (54.5% versus 68.1%, p=0.06).

Table 2.
Summary of HIV Medication Adherence and HIV Resistance in the HIV-Infected MSM, Meth-Dependent Population

Few studies have investigated the reasons for poor adherence in HIV-infected MSM who use crystal meth. A qualitative study of 20 HIV-infected MSM who believed that they had seroconverted in the context of crystal meth use revealed that crystal meth intoxication compromised one's ability to care for one's self by eating correctly, sleeping regularly, taking medications as prescribed, visiting the doctor regularly, paying bills, and going to work.11 Many participants had lost jobs in the context of crystal meth abuse, had become socially estranged from family and friends, were homeless, and chronically depressed—outcomes that may have significant implications for HIV medication adherence. Moreover, some former users reported long-term cognitive impairment, where despite having ceased crystal meth use individuals were still unable to remember to take their HIV medications appropriately. In a different qualitative study of 23 HIV-infected, crystal meth-abusing MSM all participants acknowledged that crystal meth use interfered with HIV medication adherence.13 Nonadherence was divided into planned and unplanned adherence. Planned nonadherence was used by participants as a way to regain control over their lives after being diagnosed with HIV and included taking medication vacations and avoiding the mixing of drugs. Unplanned nonadherence was closely tied to crystal meth intoxication and included the inability to maintain a schedule, and difficulty with regular eating and sleeping patterns. A cross-sectional study of 122 HIV-infected, crystal meth-using MSM (94%) or transgendered individuals on ART found that positive affect was significantly associated with the increased likelihood of reporting perfect (aOR=1.79, 95% CI 1.06–3.02, p<0.05) or near perfect (≤90%; (aOR=1.63, 95% CI 1.00–2.65, p=0.05) ART adherence in the past month.7 Conversely, negative affect was associated with weekly crystal meth use (aOR=1.76, 95% CI 1.02–3.03). These findings suggest that both crystal meth use and medication adherence may be highly tied to mood, and crystal meth use may be a means of coping with negative affect relating to one's HIV diagnosis.

HIV resistance

Crystal meth use in HIV-infected individuals has been associated with significantly increased viral loads in the age of HAART.54 Antiretroviral medications suppress viral replication only when drug concentrations are maintained at specific levels. Thus, poor adherence to antiretroviral drugs is thought to contribute to drug resistance because of decreased inhibition of viral replication. Two studies specifically address HAART resistance in HIV-infected MSM who use crystal meth. A cross-sectional study of 300 recently HIV-infected MSM crystal meth users showed that weekly crystal meth use was associated with primary drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI; OR=3.5, 95% CI 1.2–10.8, p=0.03), even after controlling for multiple sex partners, race/ethnicity, other illicit drug use, and previous use of antiretroviral drugs.55 However, no association was found between frequent crystal meth use and resistance to NRTIs or protease inhibitors. A retrospective study of 117 MSM with recent HIV infection (diagnosed within the prior 12 months) who were HAART-naïve examined HAART resistance in the context of substance abuse.9 Overall, crystal meth was the most commonly used drug during sex with 34% of participants having used crystal meth during sexual activity with their last three sexual partners. Among crystal meth users specifically, more than half had evidence of resistant virus (57% genotypic; 56% phenotypic), compared to nonusers (30% genotypic; 31% phenotypic). Meth users were four times more likely to develop phenotypic resistance (aOR=4.00, 95% CI 1.19–13.38), compared to participants who did not use crystal meth. Given that the study population was HAART naïve, these findings suggests that phenotypic resistance may be transmitted through sexual contact, which may have implications on the choice of initial HAART regimen for this subpopulation.


Drawing on the success of pharmacologic treatments for other substance dependencies (e.g., cocaine and nicotine), researchers have increasingly studied the utility of medications in treating crystal meth dependence (Table 3). Galloway et al.56 conducted a randomized controlled trial testing the efficacy of Imipramine, a tricyclic antidepressant, in treating crystal meth dependence. The intervention (150 mg/day), which was conducted among 32 crystal meth users (31% MSM, 28% HIV-infected), was not successful in reducing crystal meth use, affective status, or cravings, and no differences were seen between the intervention group (150 mg/day) and the control group (10 mg/day). Similarly, Shoptaw et al.57,58 tested the effects of selective serotonin reuptake inhibitors (SSRI) antidepressants in treating crystal meth dependence. In two separate, randomized controlled trials bupropion and sertraline were found to be no more effective than placebo in treating crystal meth dependence. However, post hoc analyses indicated that bupropion was effective in reducing crystal meth use among light users (0–2 crystal meth-positive urine samples during the 2-week baseline phase) versus heavy users (3–6 crystal meth-positive urine samples during the 2-week baseline phase), warranting further evaluation of the drug in treating light crystal meth users. Modafinil, a wakefulness medication successfully used to treat cocaine dependence, was also evaluated for its efficacy in treating crystal meth dependence in a sample of HIV-infected MSM. In a small single blinded study, McElhiney and colleagues59 tested the efficacy of modafinil combined with cognitive behavioral therapy (CBT), a psychotherapy often used to prevent substance use relapse. Among the 10 who completed treatment, 6 reduced their crystal meth use by more than 50%; however, the study was underpowered to draw any meaningful conclusions. The trial also lacked a control group, so it is not possible to determine whether preliminary efficacy was the result of modafinil or the behavioral therapy.

Table 3.
Summary of Studies on Treatment of Meth Dependence Among Mixed (e.g., HIV-Uninfected and/or Non-MSM) and HIV-Infected MSM Samples

Given the lack of effective pharmacologic treatments, researchers have studied the effects of behavioral interventions such as CBT in treating crystal meth dependence, yet minimal research has been conducted in HIV-infected MSM specifically. CBT approaches for substance dependence target the motivations for use, and aid dependent persons in developing behavioral and cognitive skills to abstain and prevent relapse. While many variations of CBT exist, the fundamental elements include understanding the internal triggers (e.g., cravings, depression, anxiety) and external triggers (e.g., exposure to drug using environment) of drug use, and developing coping skills to aid individuals in overcoming theses triggers.60 A randomized controlled trial of 978 crystal meth-dependent men and women in treatment tested the efficacy of the “Matrix Model” compared to treatment as usual (TAU; the treatment participants were already receiving) over the course of 16 weeks.61 The Matrix Model consisted of intensive CBT (36 sessions), social support groups (4 sessions), family education (12 sessions), and individual counseling (4 sessions). While both groups had more crystal meth-free urine samples at the end of treatment, at 6-month follow-up the Matrix group attended more clinical sessions, stayed in treatment longer, produced more drug-free urine samples, and had longer periods of abstinence during treatment than the TAU group. However, significant differences between the Matrix and the TAU groups were lost postintervention. Moreover, the study was conducted in a mixed sample of HIV-infected and uninfected crystal meth users and did not demonstrate efficacy in crystal meth-dependent MSM specifically.

Only one treatment study has focused on the HIV-infected crystal meth-dependent MSM population, and the outcome of this study was a reduction in high-risk behaviors, not a reduction in crystal meth use. This randomized controlled trial was conducted in a group of 341 HIV-infected MSM who had used crystal meth in the prior 2 months, and compared safe-sex behavioral counseling versus diet and exercise counseling as a control.62 Participants in both arms received eight 90-min sessions of individual therapy, during which time counseling took place. The intervention arm received training in condom use, safer sex practices in the context of crystal meth use, disclosure of HIV status to partners, and enhancement of positive social supports. The modes of education during these sessions included observation, role modeling, motivational interviewing, and rehearsing various scenarios. Primary outcomes included the total number of protected sex acts and the total number of unprotected sex acts. At 12-month follow-up those randomized to the safe-sex behavioral intervention reported significantly more protected sex acts compared to the control group (25.8% versus 18.7%, p=0.038).

Contingency management (CM) interventions have also been used to treat crystal meth abuse6369; however, there is conflicting evidence regarding CM's efficacy. CM is a psychotherapy that provides rewards (e.g., cash or vouchers exchangeable for goods) for the achievement of specific treatment goals (e.g., abstinence from drug use or treatment session attendance). CM is grounded on the principles of operant conditioning, which posits that individuals are more likely to repeat behaviors that are followed by positive outcomes. In response to increases in crystal meth-related STIs and HIV infection among MSM, the San Francisco Department of Public Health established a CM field program for crystal meth-using MSM.68 Of the 143 participants who enrolled at baseline, 77% were HIV-infected and 111 returned to participate in the 12-week CM treatment program. Participants were drug tested via urine samples 3 times per week. Participants with a crystal meth-free urine sample received a voucher that could be exchanged for goods and services that promoted a healthy, drug-free lifestyle. During the 12-week study period, 52% of participants had 12 crystal meth-free urine samples, 17% had 24 crystal meth-free samples, and only 8% had 36 crystal meth-free samples. On average, participants produced 15 of 36 (42%) crystal meth-free urine samples over the course of the study. In a similar study, CM was implemented in a community HIV prevention setting in a sample of 131 homeless, substance-dependent MSM (28% HIV-infected).66 Over the course of the 24-week intervention, both the control and the CM group received points for participating in HIV adherence activities. However, the CM arm also received points for crystal meth abstinence and health-promoting behaviors. Health-promoting behaviors included making appointments with health care providers and social workers, enrolling in educational programs, and getting and keeping a job. Points could be redeemed for goods at an onsite store. Goods most purchased were gift cards for grocery stores and restaurants. At the completion of the study, the CM group reported significantly more healthy behaviors and less crystal meth use (69% crystal meth-free urine versus 48%, p<0.05) compared to the control group. Reductions in substance use were maintained at 9- and 12-month postintervention follow-up.

Contrary to the efficacy seen in the previously reported studies, a recent randomized controlled trial of 127 crystal meth-dependent MSM (55% HIV-infected) in Seattle, WA did not show significant differences between the CM intervention and the control (referral to community resources) in reducing crystal meth use.63 The CM intervention was implemented over a 12-week period, and vouchers were provided for consecutive drug-free urine samples. Vouchers were redeemable for gift cards, goods, and services. The primary outcome was serodiscordant UAI in the prior 6 weeks. Secondary outcomes included crystal meth-free urine samples, self-reported crystal meth use, and number of serodiscordant partners. Comparing consecutive study visits, non-concordant UAI declined significantly in both study arms, with no significant differences seen between groups. Both groups were likely to provide crystal meth positive urine samples during the intervention. However, the CM group was slightly more likely to provide urine samples containing crystal meth post-intervention. Findings suggest that crystal meth dependent MSM may not benefit from stand alone CM interventions conducted outside of drug treatment.

Research comparing the efficacy of CM to CBT has been conducted among mixed samples of crystal meth users, although no trials to-date explore these interventions in an exclusively HIV-infected sample of MSM. In a randomized controlled trial of 113 crystal meth-abusing or crystal meth-dependent participants, Roll et al.67 compared the efficacy of treatment as usual (CBT control group) to treatment as usual plus CM (CM+CBT) over the course of 12 weeks. Participants were recruited from treatment clinics where participants were receiving some form of CBT therapy (e.g., the Matrix Model). The proportion of HIV-infected MSM in the sample was not commented on in this study. Those randomly assigned to the CM plus treatment as usual arm received plastic chips for every drug-free urine sample provided. These chips could be exchanged for goods and services. After 12 weeks of treatment, those in the CM+CBT group had significantly more drug free urine samples and a longer period of abstinence compared to the CBT (treatment as usual) group. Similarly, a randomized clinical trial comparing CM to CBT to CM+CBT combined was conducted in a sample of stimulant users (90% cocaine users; 10% crystal meth users) over the course of 16 weeks.70 The study did not report the number of HIV-infected or MSM participants in the sample. Stimulant use was tested three times per week via urine samples. The CM group could win vouchers for crystal meth-free urine samples worth up to $1200 over the course of the study. The CBT group received group sessions three times per week and the combined CM+CBT group received both the sessions and the vouchers. Reductions in stimulant use were observed for all groups. However, the CM groups (CM or CM+CBT) produced significantly greater retention and stimulant use reductions. At follow-up, reduced stimulant use was still observed, although differences between groups were lost. Another randomized controlled trial of 162 crystal meth-dependent MSM (60% HIV-infected), compared 4 combination treatments over the course of 16 weeks: (1) CBT alone, (2) CM alone, (3) CBT+CM, and (4) GCBT, a culturally tailored intervention for gay and bisexual crystal meth-dependent men.41,64,65,69,71 Those assigned to CBT Matrix Model met three times per week for a group session, which provided education on drug use triggers, stages of recovery, and coping strategies to avoid specific triggers. The CM group received vouchers for each drug-free urine sample, and could exchange these vouchers for goods and services. On average, participants earned $415. Participants in the CM+CBT arm received all elements of the CM and CBT interventions. The GCBT arm integrated core components of the CBT intervention with the goal of reducing HIV-related risk behaviors. Results from the study were provided across multiple articles.41,64,65,69,71 Shoptaw et al.69 reported on several crystal meth-specific outcomes and found that the groups containing the CM intervention (CM only and CM+CBT) demonstrated the most crystal meth-free urine samples, increased treatment retention, increased treatment effectiveness scores, and fewer missed urine screens. In addition, the GCBT group demonstrated the fastest reduction rate in reported unprotected receptive anal sex during treatment compared to the CBT only group. Reductions in crystal meth use and HIV risk behavior were sustained at 1-year postintervention follow-up. Jaffe et al.71 reported on crystal meth use reduction rates, indicating that the GCBT group showed the greatest rate of decline in crystal meth use compared to other groups.

New behavioral therapies, such as behavioral activation therapy (BAT) are also being explored in the treatment of crystal meth dependence. BAT is an evidence-based treatment for improving mood and increasing activity. BAT involves gradually learning how to reengage in life by identifying and actively engaging in pleasurable activities. A recent pilot study provided HIV-uninfected, crystal meth-using MSM with 10 sessions of BAT alongside HIV risk reduction counseling in order to reduce HIV-related risk behaviors and crystal meth.72 At 3-month follow-up there was significant reduction in UAI, crystal meth use, and depressive symptoms. While results are promising, this potential intervention requires more rigorous testing in the context of a randomized controlled trial.


HIV-infected, MSM who use crystal meth are a unique population. They are more likely to have high risk sexual behaviors, STIs, and serodiscordant UAI compared to HIV-infected MSM who do not use crystal meth, and also relative to HIV-uninfected, crystal meth-using MSM. Their reasons for use may in part relate to their HIV diagnosis, whether they use crystal meth for sexual enhancement, to escape social isolation, or to feel more physically energetic. Medication adherence in this population is also notably low, which may contribute to the transmission of resistant virus that has been seen in newly infected MSM who use crystal meth. Given the lack of effective treatment options, providers may not have the tools to adequately address this issue, especially in the primary care setting.

The treatment studies, although well-designed, have failed to show a sustained impact in decreasing crystal meth use; no medications have proven effective in this population. A phase 2 clinical trial is currently underway evaluating the role of extended release naltrexone (Vivitrol®, Alkermes, Waltham, MA) in crystal meth-dependent individuals.73 Early animal models suggest that there may be a role of varenicline (Chantix®, Pfizer, New York, NY) in the treatment of crystal meth abuse.74 Meanwhile, the role of behavioral therapies is still in question. Some studies have demonstrated the potential benefit of contingency management for the treatment of crystal meth dependence. However, key limitations of CM include failure of the intervention to adequately address participants' mental health needs or work with participants to develop relapse prevention plans postintervention. Interventions testing the efficacy of CM alongside other therapies such as CBT have proven modestly effective in reducing crystal meth dependence,61,6668 however, these have not been routinely adopted into clinical practice due to cost75 and required infrastructure. Some studies have focused on decreasing UAI as the primary outcome. Reducing UAI is not only meaningful in reducing transmission of resistant HIV, but also has been easier to achieve in prior studies as opposed to reductions in crystal meth use.

When looking at these treatment studies it is important to recognize that many behavioral therapy trials were not exclusively in an HIV-infected MSM population.5658,61,67,70 The HIV-infected population may have different relationships with medical providers and variable attitudes regarding adherence and healthy behaviors compared to the HIV-uninfected population. Thus, their response to behavioral counseling and treatment may be different than those that are uninfected. When focusing on HIV-infected individuals, poor health-related outcomes such as increased viral loads, increased transmission or resistant HIV, and decreased CD4 counts must be emphasized. Future studies that focus on behavioral interventions for HIV-infected individuals will need to explore these motivators in more detail.

The limitations of the current review mostly pertain to the methodological quality of the available studies. Many studies regarding risk behavior and adherence were cross-sectional or retrospective studies. Thus, causation cannot truly be determined. Furthermore, substance use, medication adherence, and sexual behaviors were often determined through self-report rather than more objective means such as toxicology screens and STI testing. Only one study used MEMS caps as a reliable marker of adherence.53 Given the sensitive nature of these behaviors, participants may have under-reported their sexual and crystal meth-using behaviors.

Finally, there is much geographic variation in patterns of crystal meth use. Many studies in this review were performed in California, although some in Seattle and other locations. As a result, it may be difficult to generalize or apply them to different geographic regions. We limited our search to English-language studies based in the United States to account for this geographic variation, which would likely have been even more prominent international studies were included.

The treatment of HIV-infected MSM who use crystal meth must remain a priority among health care providers. By reducing crystal meth use, we can have an impact on individual HIV-related outcomes, and subsequently reduce HIV transmission rates on a population level. At this time, there is no clear treatment guidance regarding the best ways to reduce crystal meth use. As such, we must continue with research efforts that develop and test novel strategies. In the short term, however, the available data suggest that we continue to focus our efforts on decreasing high-risk behaviors in this population. Furthermore, among providers, it is critical that we continue to assess our patients' substance use. Even though there are no clear treatment options, adherence, risk reduction counseling, and linkage to care should remain an important focus in caring for this vulnerable population.

Author Disclosure Statement

No competing financial interests exist. This publication was made possible with help from the Harvard University Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NCCAM, and FIC. This publication was also supported in part by Award Number R34DA031028 (PI:Mimiaga) from the National Institute On Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Drug Abuse or the National Institutes of Health. MP was supported by National Institutes of Mental Health R01 (5R01MH084757-03) and TNC-CDAAR (P30DA013868).


1. CDC. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2008. [Dec 3;2009 ]. Estimates of New HIV Infections in the United States.
2. CDC. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2007. [Dec 3;2009 ]. Methamphetamine Use and Risk for HIV/AIDS.
3. Buchacz K. McFarland W. Kellogg T, et al. Amphetamine use is associated with increased HIV incidence among men who have sex with men in San Francisco. AIDS. 2005;19:1423–1424. [PubMed]
4. Shoptaw S. Reback C. Associations between methamphetamine use and hiv among men who have sex with men: A model for guiding public policy. J Urban Health. 2006;83:1151–1157. [PMC free article] [PubMed]
5. Bousman CA. Cherner M. Ake C, et al. Negative mood and sexual behavior among non-monogamous men who have sex with men in the context of methamphetamine and HIV. J Affect Disord. 2009;119:84–91. [PMC free article] [PubMed]
6. Carey J. Mejia R. Bingham T, et al. Drug use, high-risk sex behaviors, and increased risk for recent HIV infection among men who have sex with men in Chicago and Los Angeles. AIDS Behav. 2009;13:1084–1096. [PubMed]
7. Carrico A. Johnson M. Colfax G. Moskowitz J. Affective correlates of stimulant use and adherence to anti-retroviral therapy among HIV-positive methamphetamine users. AIDS Behav. 2010;14:769–777. [PMC free article] [PubMed]
8. Forrest D. Metsch L. LaLota M. Cardenas G. Beck D. Jeanty Y. Crystal Methamphetamine use and sexual risk behaviors among HIV-positive and HIV-negative men who have sex with men in South Florida. J Urban Health. 2010;87:480–485. [PMC free article] [PubMed]
9. Gorbach PM. Drumright LN. Javanbakht M, et al. Antiretroviral drug resistance and risk behavior among recently HIV-infected men who have sex with men. J Acquir Immune Defic Syndr. 2008;47:639–643. [PubMed]
10. Marquez C. Mitchell SJ. Hare CB. John M. Klausner JD. Methamphetamine use, sexual activity, patient–provider communication, and medication adherence among HIV-infected patients in care, San Francisco 2004–2006. AIDS Care. 2009;21:575–582. [PubMed]
11. Mimiaga MJ. Fair AD. Mayer KH, et al. Experiences and sexual behaviors of HIV-infected MSM who acquired HIV in the context of crystal methamphetamine use. AIDS Educ Prev. 2008;20:30–41. [PubMed]
12. Morin S. Myers J. Shade S. Koester K. Maiorana A. Rose C. Predicting HIV transmission risk among HIV-infected patients seen in clinical settings. AIDS Behav. 2007;11:6–16. [PubMed]
13. Reback CJ. Larkins S. Shoptaw S. Methamphetamine abuse as a barrier to HIV medication adherence among gay and bisexual men. AIDS Care. 2003;15:775–785. [PubMed]
14. Semple SJ. Patterson TL. Grant I. Motivations associated with methamphetamine use among HIV men who have sex with men. J Subst Abuse Treat. 2002;22:149–156. [PubMed]
15. Semple SJ. Strathdee SA. Zians J. Patterson TL. Social and behavioral characteristics of HIV-positive MSM who trade sex for methamphetamine. Am J Drug Alcohol Abuse. 2010;36:325–331. [PMC free article] [PubMed]
16. Mayer KH. O'Cleirigh C. Skeer M, et al. Which HIV-infected men who have sex with men in care are engaging in risky sex and acquiring sexually transmitted infections: Findings from a Boston community health centre. Sex Transm Infect. 2010;86:66–70. [PubMed]
17. Mansergh G. Shouse RL. Marks G, et al. Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive and insertive anal sex, respectively, in a sample of men who have sex with men. Sex Transm Infect. 2006;82:131–134. [PMC free article] [PubMed]
18. Halkitis P. Shrem M. Martin F. Sexual behavior patterns of methamphetamine-using gay and bisexual men. Subst Use Misuse. 2005;40:703–719. [PubMed]
19. Wohl A. Frye D. Johnson D. Demographic characteristics and sexual behaviors associated with methamphetamine use among MSM and non-MSM diagnosed with AIDS in Los Angeles County. AIDS Behav. 2008;12:705–712. [PubMed]
20. VanDevanter N. Duncan A. Burrell-Piggott T, et al. The influence of substance use, social sexual environment, psychosocial factors, and partner characteristics on high-risk sexual behavior among young black and latino men who have sex with men living with HIV: A qualitative study. AIDS Patient Care STDs. 2011;25:113–121. [PMC free article] [PubMed]
21. Halkitis P. Mukherjee P. Palamar J. Longitudinal modeling of methamphetamine use and sexual risk behaviors in gay and bisexual men. AIDS Behav. 2009;13:783–791. [PubMed]
22. Spindler HH. Scheer S. Chen SY, et al. Viagra, methamphetamine, and HIV risk: Results From a probability sample of MSM, San Francisco. Sex Transm Dis. 2007;34:586–591. [PubMed]
23. Schwarcz S. Scheer S. McFarland W, et al. Prevalence of HIV infection and predictors of high-transmission sexual risk behaviors among men who have sex with men. Am J Public Health. 2007;97:1067–1075. [PubMed]
24. Semple S. Zians J. Grant I. Patterson T. Sexual risk behavior of HIV-positive methamphetamine-using men who have sex with men: The role of partner serostatus and partner type. Arch Sex Behav. 2006;35:461–471. [PubMed]
25. Semple S. Zians J. Grant I. Patterson T. Sexual compulsivity in a sample of HIV-positive methamphetamine-using gay and bisexual men. AIDS Behav. 2006;10:587–598. [PubMed]
26. Wong W. Chaw JK. Kent CK. Klausner JD. Risk Factors for early syphilis among gay and bisexual men seen in an STD clinic: San Francisco, 2002–2003. Sex Transm Dis. 2005;32:458–463. [PubMed]
27. Hatfield LA. Horvath KJ. Jacoby SM. Simon Rosser BR. Comparison of substance use and risky sexual behavior among a diverse sample of urban, HIV-positive men who have sex with men. J Addict Dis. 2009;28:208–218. [PMC free article] [PubMed]
28. Patterson T. Semple S. Zians J. Strathdee S. Methamphetamine-using HIV-positive men who have sex with men: Correlates of polydrug use. J Urban Health. 2005;82:i120–i126. [PMC free article] [PubMed]
29. Semple SJ. Strathdee SA. Zians J. Patterson TL. Sexual risk behavior associated with co-administration of methamphetamine and other drugs in a sample of HIV-positive men who have sex with men. Am J Addict. 2009;18:65–72. [PMC free article] [PubMed]
30. Semple S. Zians J. Strathdee S. Patterson T. Sexual marathons and methamphetamine use among HIV-positive men who have sex with men. Arch Sex Behav. 2009;38:583–590. [PMC free article] [PubMed]
31. Semple S. Strathdee S. Zians J. Patterson T. Factors associated with sex in the context of methamphetamine use in different sexual venues among HIV-positive men who have sex with men. BMC Public Health. 2010;10:178. [PMC free article] [PubMed]
32. Whittington W. Collis T. Dithmer-Schreck D, et al. Sexually transmitted diseases and Human immunodeficiency virus–discordant partnerships among men who have sex with men. Clin Infect Dis. 2002;35:1010–1017. [PubMed]
33. Semple SJ. Patterson TL. Grant I. Binge use of methamphetamine among HIV-positive men who have sex with men: Pilot data and HIV prevention implications. AIDS Educ Prev. 2003;15:133. [PubMed]
34. Rudy ET. Shoptaw S. Lazzar M. Bolan RK. Tilekar SD. Kerndt PR. Methamphetamine use and other club drug use differ in relation to HIV status and risk behavior among gay and bisexual men. Sex Transm Dis. 2009;36:693–695. [PMC free article] [PubMed]
35. Molitor F. Truax SR. Ruiz JD. Sun RK. Association of methamphetamine use during sex with risky sexual behaviors and HIV infection among non-injection drug users. West J Med. 1998;168:93–97. [PMC free article] [PubMed]
36. Brewer DD. Golden MR. Handsfield HH. Unsafe sexual behavior and correlates of risk in a probability sample of men who have sex with men in the era of highly active antiretroviral therapy. Sex Transm Dis. 2006;33:250–255. [PubMed]
37. Drumright LN. Strathdee SA. Little SJ, et al. Unprotected anal intercourse and substance use before and after HIV diagnosis among recently HIV-infected men who have sex with men. Sex Transm Dis. 2007;34:401–407. [PubMed]
38. Frosch D. Shoptaw S. Huber A. Rawson RA. Ling W. Sexual HIV risk among gay and bisexual male methamphetamine abusers. J Subst Abuse Treat. 1996;13:483–486. [PubMed]
39. Menza TW. Hughes JP. Celum CL. Golden MR. Prediction of HIV acquisition among men who have sex with men. Sex Transm Dis. 2009;36:547–555. [PMC free article] [PubMed]
40. Morin SF. Steward WT. Charlebois ED, et al. Predicting HIV transmission risk among HIV-infected men who have sex with men: Findings from the Healthy Living Project. J Acquir Immune Defic. 2005;40:226–235. [PubMed]
41. Peck JA. Shoptaw S. Rotheram-Fuller E. Reback CJ. Bierman B. HIV-associated medical, behavioral, and psychiatric characteristics of treatment-seeking, methamphetamine-dependent men who have sex with men. J Addict Dis. 2005;24:115–132. [PubMed]
42. Plankey MW. Ostrow DG. Stall R, et al. The relationship between methamphetamine and popper use and risk of HIV seroconversion in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 2007;45:85–92. [PMC free article] [PubMed]
43. Thiede H. Jenkins RA. Carey JW, et al. Determinants of recent HIV infection among Seattle-area men who have sex with men. Am J Public Health. 2009;99:S157–164. [PubMed]
44. Taylor MM. Aynalem G. Smith LV. Montoya J. Kerndt P. Methamphetamine use and sexual risk behaviours among men who have sex with men diagnosed with early syphilis in Los Angeles County. Int J STD AIDS. 2007;18:93–97. [PubMed]
45. Shoptaw S. Reback CJ. Freese TE. Patient characteristics, HIV serostatus, and Risk behaviors among gay and bisexual males seeking treatment for methamphetamine abuse and dependence in Los Angeles. J Addict Dis. 2001;21:91–105. [PubMed]
46. Nettles CD. Bentosch EG. Uban KA. Sexual risk behaviors among men who have sex with men using erectile dysfunction medications. AIDS Patient Care STDs. 2009;23:1017–1023. [PubMed]
47. Nakamura N. Semple SJ. Strathdee SA. Patterson TL. Methamphetamine initiation among HIV-positive gay and bisexual men. AIDS Care. 2009;21:1176–1184. [PMC free article] [PubMed]
48. Halkitis PN. Fischgrund BN. Parsons JT. Explanations for methamphetamine use among gay and bisexual men in New York City. Subst Use Misuse. 2005;40:1331–1345. [PubMed]
49. Arnsten JH. Demas PA. Grant RW, et al. Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. J Gen Intern Med. 2002;17:377–381. [PMC free article] [PubMed]
50. Lucas GM. Cheever LW. Chaisson RE. Moore RD. Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection. J Acquir Immune Defic Syndr. 2001;27:251–259. [PubMed]
51. Lucas GM. Griswold M. Gebo KA. Keruly J. Chaisson RE. Moore RD. Illicit drug use and HIV-1 disease progression: A longitudinal study in the era of highly active antiretroviral therapy. Am J Epidemiol. 2006;163:412–420. [PubMed]
52. Robison LS. Westfall AO. Mugavero MJ, et al. Short-term discontinuation of HAART regimens more common in vulnerable patient populations. AIDS Res Human Retroviruses. 2008;24:1347–1355. [PMC free article] [PubMed]
53. Hinkin C. Barclay T. Castellon S, et al. Drug use and medication adherence among HIV-1 infected individuals. AIDS Behav. 2007;11:185–194. [PMC free article] [PubMed]
54. Ellis RJ. Childers ME. Cherner M. Lazzaretto D. Letendre S. Grant I. Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy. J Infect Dis. 2003;188:1820–1826. [PubMed]
55. Colfax GN. Vittinghoff E. Grant R. Lum P. Spotts G. Hecht FM. Frequent methamphetamine use is associated with primary non-nucleoside reverse transcriptase inhibitor resistance. AIDS. 2007;21:239–241. [PubMed]
56. Galloway GP. Newmeyer J. Knapp T. Stalcup SA. Smith D. A controlled trial of imipramine for the treatment of methamphetamine dependence. J Subst Abuse Treat. 1996;13:493–497. [PubMed]
57. Shoptaw S. Heinzerling KG. Rotheram-Fuller E, et al. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug Alcohol Depend. 2008;96:222–232. [PubMed]
58. Shoptaw S. Huber A. Peck J, et al. Randomized, placebo-controlled trial of sertraline and contingency management for the treatment of methamphetamine dependence. Drug Alcohol Depend. 2006;85:12–18. [PubMed]
59. McElhiney MC. Rabkin JG. Rabkin R. Nunes EV. Provigil (Modafinil) Plus cognitive behavioral therapy for methamphetamine use in HIV+ gay men: A pilot study. Am J Drug Alcohol Abuse. 2009;35:34–37. [PubMed]
60. Drumright LN. Colfax GN. HIV risk and prevention for non-injection substance users. In: Mayer KH, editor. HIV Prevention: A Comprehensive Approach. London; Elsevier: 2009. pp. 342–344.
61. Rawson RA. Marinelli-Casey P. Anglin MD, et al. A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence. Addiction. 2004;99:708–717. [PubMed]
62. Mausbach BT. Semple SJ. Strathdee SA. Zians J. Patterson TL. Efficacy of a behavioral intervention for increasing safer sex behaviors in HIV-positive MSM methamphetamine users: Results from the EDGE study. Drug Alcohol Depend. 2007;87:249–257. [PMC free article] [PubMed]
63. Menza T. Jameson D. Hughes J. Colfax G. Shoptaw S. Golden M. Contingency management to reduce methamphetamine use and sexual risk among men who have sex with men: A randomized controlled trial. BMC Public Health. 2010;10:774. [PMC free article] [PubMed]
64. Peck J. Reback C. Yang X. Rotheram-Fuller E. Shoptaw S. Sustained reductions in drug use and depression symptoms from treatment for drug abuse in methamphetamine-dependent gay and bisexual men. J Urban Health. 2005;82:i100–i108. [PMC free article] [PubMed]
65. Reback CJ. Larkins S. Shoptaw S. Changes in the meaning of sexual risk behaviors among gay and bisexual male methamphetamine abusers before and after drug treatment. AIDS Behav. 2004;8:87–98. [PubMed]
66. Reback CJ. Peck JA. Dierst-Davies R. Nuno M. Kamien JB. Amass L. Contingency management among homeless, out-of-treatment men who have sex with men. J Subst Abuse Treat. 2010;39:255–263. [PMC free article] [PubMed]
67. Roll JM. Petry NM. Stitzer ML, et al. Contingency Management for the treatment of methamphetamine use disorders. Am J Psychiatry. 2006;163:1993–1999. [PubMed]
68. Shoptaw S. Klausner J. Reback C, et al. A public health response to the methamphetamine epidemic: The implementation of contingency management to treat methamphetamine dependence. BMC Public Health. 2006;6:214. [PMC free article] [PubMed]
69. Shoptaw S. Reback CJ. Peck JA, et al. Behavioral treatment approaches for methamphetamine dependence and HIV-related sexual risk behaviors among urban gay and bisexual men. Drug Alcohol Depend. 2005;78:125–134. [PubMed]
70. Rawson RA. McCann MJ. Flammino F, et al. A comparison of contingency management and cognitive-behavioral approaches for stimulant-dependent individuals. Addiction. 2006;101:267–274. [PubMed]
71. Jaffe A. Shoptaw S. Stein J. Reback CJ. Rotheram-Fuller E. Depression ratings, reported sexual risk behaviors, and methamphetamine use: Latent growth curve models of positive change among gay and bisexual men in an outpatient treatment program. Exp Clin Psychopharmacol. 2007;15:301–307. [PubMed]
72. In: Mimiaga MJ, editor; Reisner SL, editor; Pantalone DW, editor; O'Cleirigh C, editor; Mayer KH, editor; Safren SA, editor. An Open Phase Pilot of Behavioral Activation Therapy and Risk Reduction Counseling for MSM with Crystal Methamphetamine Abuse at Risk for HIV Infection; Seattle, WA. Society of Behavioral Medicine 2010 Annual Meeting;
73. California Pacific Medical Center Research Institute. Study of Naltrexone for Methamphetamine Addicition. National Library of Medicine (US) 2009. [Jun 15;2011 ]. ClinicalTrials.gov [Internet]
74. Desai RI. Bergman J. Drug discrimination in methamphetamine-traine rat: Effects of cholinergic nicotinic compounds. J Pharmacol Exp Ther. 2010;335:807–816. [PubMed]
75. Kirby KC. Benishek LA. Dugosh KL. Kerwin ME. Substance abuse treatment providers' beliefs and objections regarding contingency management: Implications for dissemination. Drug Alcohol Depend. 2006;85:19–27. [PubMed]

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