Promoting HIV care continuum outcomes among people who use drugs and alcohol: a systematic review of randomized trials evaluating behavioral HIV care interventions published from 2011 to 2023

Ten articles reflected studies wherein substance-using populations were intentionally targeted, while one reflected a study with a population that incidentally used substances. Of the former, four studies involved the use of at least one of several substances, including alcohol, opioids, stimulants, and/or marijuana, among others; four involved injection drug use only; one involved methamphetamine use only; one involved alcohol use only. The population that used substances incidentally used alcohol, injection drugs, and non-injection drugs. Eight studies utilized a two-arm RCT design, two used a three-arm RCT design, and one used a four-arm RCT design. Geographic settings for studies included the United States (US; n = 5), South Africa (n = 1), Estonia (n = 1), Vietnam (n = 1), and Russia (n = 2); one study spanned Indonesia, Vietnam, and Ukraine. Moreover, differences between experimental arms were sometimes present, which we note below, and studies often used both objective (e.g., blood testing, clinical records) and subjective measures (e.g., self-report) to assess outcomes (Table 2).

To provide a comprehensive overview of the findings from this systematic review, we first focus on describing each of the eleven studies in detail (organized by the primary substance used by the sample). For each study, we report the basic intervention components, sample, substance use-related characteristics, and significant intervention effects and other relevant findings, including outcomes that do not directly pertain to the HIV care continuum (e.g., reductions in substance use). Additional information for each study is described in Tables 1 and 2. At the end of this section we also describe overall findings of intervention effects on HIV care continuum outcomes. Results from the risk-of-bias assessment are described for each study and are summarized in Table 3. Overall risk-of-bias was deemed to be “low” across the studies, with the exception of three studies where there were “some concerns”.

Metsch et al. (2016) assessed the effect of a patient navigation intervention with and without financial incentives to promote ART uptake, ART adherence, and viral suppression among hospitalized PLHIV with elevated viral loads and past-year opioid, stimulant, or heavy alcohol use in 11 urban hospitals across the US [46]. An additional outcome involved outpatient care with an HIV specialist, which we considered retention in care [46]. At baseline, 59% of participants evidenced harmful/hazardous alcohol use; 97% had documented stimulant, opioid, or other drug use; 18% had injected drugs in the past year; and 70% evidenced severe substance use [46]. HIV care continuum outcomes. At six-month follow-up, more navigation-with-incentives participants were virally suppressed compared to control and navigation-only participants, and more navigation-with-incentives participants and navigation-only participants had attended HIV care visits and taken ART than control participants [46]. There was no intervention effect on viral suppression at 12 months [46]. Other outcomes. At six-month follow-up, more navigation-with-incentives and navigation-only participants received professional substance use disorder treatment than control participants [46]. There was no effect on other substance use outcomes at 12 months [46]. Risk-of-bias for this study was judged to be low (see Table 3).

Myers and colleagues (2018) assessed the effect of a patient navigation-enhanced HIV case management intervention to promote linkage to HIV care, retention in HIV care, and viral suppression, as well as reduce risky sex and drug use behavior among PLHIV reporting prior or current substance use and who were recently arrested and released from San Francisco County Jail [47]. At baseline, 94% of participants reported alcohol use in the 30 days prior to jail, 50% of whom reported alcohol use more than weekly before jail; 94% reported drug use in the 30 days prior to jail, 76% of whom reported weekly drug use before jail [47]. Methamphetamine use was the most reported drug used (63%; 40% used more than once per week), followed by crack-cocaine (57%; 37% used more than once per week) and heroin (30%; 13% used more than once per week) [47]. Thirty-three percent met criteria for alcohol abuse, 85% met criteria for substance abuse, with 8% meeting criteria for severe substance abuse [47]. Weekly drug use and using methamphetamines more than once per week in the 30 days before jail were significantly higher in the intervention group than in the control group [47]. HIV care continuum outcomes. Intervention participants were more likely to be linked to care within 30 days upon release and be retained in care over the subsequent 12 months [47]. Those who received substance dependence treatment in jail were more likely to be linked to care within 30 days upon release and be retained in care over the subsequent 12 months [47]. There was no effect on viral suppression [47]. Other outcomes. Intervention participants reported less risky sex at 12-month follow-up [47]. There was no intervention effect on alcohol or drug use behaviors [47]. Risk-of-bias for this study was judged to be low (see Table 3).

Satre et al. (2019) assessed the effect of motivational interviewing intervention (vs. emailed feedback vs. usual care) to reduce unhealthy alcohol use, alcohol problems, and drug use, and promote ART-adherence and viral load control among PLHIV with past-year unhealthy alcohol use recruited from an HIV primary care clinic in San Francisco [48]. At baseline, roughly 57% of participants were at high risk for alcohol use problems, and roughly 25% met criteria for alcohol dependence (no cross-arm differences) [48]. HIV care continuum outcomes. There were no effects on ART adherence or viral load control [48]. Other outcomes. There were declines in alcohol misuse within each arm but not between arms [48]. At the six-month follow-up, motivationally interviewed participants reported lower drug use/prescription drug misuse (excluding marijuana) than those in other arms [48]. Among participants reporting low importance of reducing alcohol use at baseline, those receiving motivational interviewing reported lower alcohol use at 12 months compared to those in other arms [48]. Risk-of-bias for this study was judged to be low (see Table 3).

Wechsberg et al. (2019) assessed the effect of an intervention (risk reduction and gender power) to reduce drug and alcohol use, gender-based violence, and sexual risk, and to promote linkage to HIV care, ART uptake, viral suppression, and sexual negotiation among Black women living with HIV who used at least one substance weekly for the past three months in Pretoria, South Africa [49]. At baseline, 32% of participants reported frequent heavy drinking (with nine days of binge drinking during the prior 30 days) and daily drug use; 31% tested positive for marijuana, 18% tested positive for opiates, and 14% tested positive for cocaine [49]. Also, at baseline, fewer intervention participants reported frequent heavy drinking (including days of binge drinking) than control participants, and fewer control participants reported daily drug use and tested positive for marijuana, opiates, and cocaine than intervention participants [49]. HIV care continuum outcomes. At 12-month follow-up, more intervention participants had undetectable viral load compared to control participants; there was no intervention effect on linkage to HIV care (among newly diagnosed, not-yet-linked participants) or ART uptake [49]. Other outcomes. At six-month follow-up, intervention participants reported decreases in alcohol use and physical and sexual intimate partner violence, increases in condom use, more frequent condom negotiation, and sex refusal without a condom with a partner in the past three months [49]. At the 12-month follow-up, intervention participants reported decreased emotional intimate partner violence [49]. Risk-of-bias for this study was judged to be low (see Table 3).

Uuskula and colleagues (2018) was the one study identified in this review that incidentally targeted a substance-using sample (most of the participants reported substance use). The study assessed the effect of an education and strengths-based counseling intervention on ART adherence and viral suppression among PLHIV receiving routine HIV clinical care from two infectious disease clinics in Tallinn and Kohtla-Järve, Estonia [50]. Roughly 80% of participants had problematic alcohol use, 18% reported current injection drug use, 17% reported current non-injection drug use, and 15% reported being currently on opioid agonist therapy (with no cross-arm differences) [50]. HIV care continuum outcomes. At the 12-month follow-up, ART adherence (≥ 95%) was marginally higher for those in the intervention group relative to the control group [50]. Among those with suboptimal ART adherence at baseline, more intervention participants reported optimal adherence at 12 months than control participants [50]. There was no effect on viral load [50]. Other outcomes. At 12 months, intervention participants viewed ART more favorably than control participants [50]. Risk-of-bias for this study was judged to be low (see Table 3).

Go and colleagues (2017) assessed the effect of a multilevel stigma-reduction intervention on ART uptake and survival among men who inject drugs (had injected in the past six months) in Thai Nguyen, Vietnam [51]. At baseline, 54% reported daily injection drug use in the past three months, 18% reported prior overdosing, and 31% had previously received drug treatment (no cross-arm differences) [51]. HIV-care continuum outcomes. Participants in the community plus individual-level intervention were more likely to initiate ART than standard-of-care participants [51]. Other outcomes. Among participants with a CD4 cell count < 200 cells/mm³ (ART-eligible threshold at the time) and not on ART at baseline, those in the community plus individual-level intervention had lower mortality than standard-of-care participants [51]. There were some concerns around risk-of-bias for this study (only in the domain of selection of the reported result), as the outcome analyzed in this paper was not a pre-defined primary or secondary outcome.

Miller et al. (2018) assessed the effect of an integrated harm reduction, systems navigation, and psychosocial counseling intervention to promote uptake and use of ART and medication-assisted drug treatment, and improve viral load suppression among PLHIV who inject drugs with elevated viral load in Kyiv, Ukraine; Thai Nguyen, Vietnam; and Jakarta, Indonesia [52]. HIV care continuum outcomes. At 12-month follow-up, uptake and use of ART and viral suppression were all higher for intervention participants than control participants [52]. Other outcomes. At 12-month follow-up, medication-assisted drug treatment was higher, and mortality was lower for intervention participants relative to control participants [52]. Risk-of-bias for this study was judged to be low (see Table 3).

Samet and colleagues (2019) assessed the effect of a peer-led strengths-based case management intervention to promote linkage to care, retention in care, and CD4 cell count testing at 12 months among PLHIV who inject drugs hospitalized at City Addiction Hospital in St. Petersburg, Russia [53]. Other outcomes included appropriate HIV care (prescribed ART or a second CD4 cell count if CD4 > 350 cells/µL) and self-reported hospitalizations at 12 months [53]. HIV care continuum outcomes. At 6-month follow-up, more intervention participants had been linked to HIV care than control participants, and at 12-month follow-up, more intervention participants had received appropriate HIV care than control participants [53]. There was no effect on CD4 cell count or retention in care [53]. Other outcomes. There was no effect on self-reported hospitalizations at 12 months [53]. Risk-of-bias for this study was judged to be low (see Table 3).

Samet et al. (2023) evaluated a multicomponent version [54] of the intervention tested in the RCT described above [53]. The 2023 RCT applied an intervention approach that combined peer-led strengths-based case management with rapid access to ART and receipt of naltrexone, a medication for opioid use disorder [54]. Like the prior study, the intervention was evaluated among PLHIV who inject drugs hospitalized at City Addiction Hospital in St. Petersburg, Russia. The primary outcome was viral suppression at the study endpoint (12-month follow-up). Secondary outcomes included ART initiation, change in CD4 cell count, and retention in HIV care. HIV care continuum outcomes. At study endpoint, a significantly larger proportion of participants in the intervention group relative to the control group had an undetectable viral load. Participants in the intervention group also had significantly higher odds of ART initiation and retention in HIV care. No changes were observed for CD4 cell count across follow-up [54]. Other outcomes. Clinically meaningful differences in opioid abstinence were observed between the two study arms at 6 and 12 months, but these differences were not statistically significant [54]. Risk-of-bias for this study was judged to be low (see Table 3).

Parsons et al. (2018) assessed the effect of motivational interviewing plus cognitive behavioral therapy intervention on reducing methamphetamine use, condomless anal sex, ART adherence, viral suppression, and immune function (increased CD4 cell count) among cisgender sexual minority men living with HIV who use methamphetamines with suboptimal ART-adherence in New York City [55]. At baseline, participants reported methamphetamine use an average of roughly six days in the past month (no cross-arm differences) [55]. HIV care continuum outcomes. At 3-, 6-, 9-, and 12-month follow-ups, intervention and control participants evidenced increased ART adherence and CD4 cell count (and lower viral load) compared to baseline, but there was no difference between arms [55]. Moderation by Information-Motivation-Behavior class (identified in a prior study) emerged: among participants in the “global barriers” class (i.e., those with global barriers to changing their methamphetamine use and medication adherence), those in the intervention had a greater improvement in ART adherence than those in the control condition [55]. Other outcomes. At 3-, 6-, 9-, and 12-month follow-ups, intervention and control participants evidenced reduced substance use and condomless anal sex, but there was no difference between arms [55]. There were some concerns around risk-of-bias for this study (only in the domain of selection of the reported result), as the study did not assess pre-defined primary or secondary outcomes.

Attonito and colleagues (2020) assessed the effect of a holistic health intervention to improve ART adherence and viral load among PLHIV reporting harmful/hazardous drinking recruited from substance abuse treatment facilities and HIV care and service organizations in Miami, Florida [56]. An additional outcome was HIV service utilization, which we considered retention in care [56]. Forty-six percent of participants reported prior treatment for alcohol use [56]. HIV care continuum outcomes. At six-month follow-up, intervention participants were more likely to report optimal ART adherence (≥ 95%) and undetectable viral load. HIV service utilization improved for both arms, but there was no difference between arms [56]. Other outcomes. At six-month follow-up, intervention participants were more likely to report greater social support than control participants [56]. There were some concerns around risk-of-bias for this study (in the domains of measurement of the outcome and selection of the reported result), as the HIV care outcomes analyzed in this paper relied solely on self-report, and the study did have pre-defined primary or secondary outcomes.

We examined the overall efficacy of the different studies in promoting HIV care continuum outcomes. All of the studies assessed at least two different HIV care outcomes (see Table 2). Of the eleven studies reviewed, only two found statistically significant intervention effects on all HIV care outcomes that were examined [51, 52]. These two studies were among the studies included in this review that focused on people who inject drugs and were conducted outside the US. The interventions in these two studies applied a multi-level approach. Specifically, Miller and colleagues applied harm reduction, systems navigation and psychosocial counseling to promote HIV care outcomes [52]; whereas Go and colleagues compared community- vs. -individual-level interventions [51]. Two studies did not find any significant effects on the HIV care outcomes that were examined [48, 55]. The interventions in these studies were applied solely at the individual level, and were the only studies in this review that relied mainly on motivational interviewing techniques as the intervention approach. The other seven studies found mixed effects, in that significant differences were observed between intervention and comparison arms for one or more HIV care outcomes, but not for others (e.g., for linkage to care but not CD4 cell count). The most commonly examined HIV care outcome was viral suppression, measured in nine (82%) of the eleven studies. Out of these nine studies, four (44%) found significant intervention effects on viral suppression at study endpoint [49, 52, 54, 56]. However, there were some concerns regarding risk-of-bias in one of the three studies [56].