A target for harm reduction in HIV: reduced illicit drug use is associated with increased viral suppression.

By Lauren Strand

In the midst of a fatal drug epidemic and shifting drug policy in the United States, there is continued interest in the relationship between illicit drug use and negative health outcomes. Because substance use is difficult to characterize in individuals, studies often target sub-populations with more substantial and better-documented substance use profiles. One example is people living with HIV, in whom substance use has been associated with poor engagement in the HIV care continuum, lower likelihood of receiving antiretroviral therapy, reduced adherence to therapy, and increased disease-related mortality. Recently I collaborated on a study finding that reduction in frequency of illicit opioid and methamphetamine use is associated with viral suppression among people living with HIV. Since viral suppression is an important consideration for individual’s health as well as disease transmission, this finding has important policy implications for harm-reduction around substance use frequency.

This work was spearheaded by Robin Nance and Dr. Maria Esther Perez Trejo and advised by Dr. Heidi Crane and Dr. Chris Delaney, colleagues and mentors of mine during my time at the Collaborative Health Studies Coordinating Center (University of Washington). The publication in Clinical Infectious Diseases focuses on the longitudinal relationship between reducing illicit drug use frequency and a key biomarker in HIV, viral load (VL), among people living with HIV. This study used longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Sites (CNICS) cohort. CNICS is an ongoing observational study consisting of more than 35,000 people living with HIV receiving primary care at one of eight sites (Seattle, San Francisco, San Diego, Cleveland, Chapel Hill, Birmingham, Baltimore, and Boston). Importantly, CNICS provides peer-reviewed open access to patient data including clinical outcomes, biological data, and patient-reported outcomes. This study also used individual data in four studies from the Criminal Justice Seek, Test, Treat, and Retain (STTR) collaboration. STTR is an effort to combines data from involved observational studies and trials to improve outcomes along the HIV care continuum for people involved in some part of the criminal justice system. One example is individuals recently released from jail who have struggled in the past with substance use disorders.

Within CNICS, substance use was collected at clinical assessment via tablets approximately every six months with instruments including the modified Alcohol, Smoking, and Substance Involvement Screening Test and the Alcohol Use Disorders Identification Test. Drug use was defined as frequency of use in the last 30 days and was further categorized according to longitudinal trends from baseline: abstinence (no use at baseline or follow-up), reduction in use without abstinence (use at baseline that has declined at follow-up), and non-decreasing (similar or increased use). Drug categories were marijuana, cocaine/crack, methamphetamine, and heroin/other illicit opioids.  Viral suppression was defined as an undetectable VL (<=400 copies/mL). Analytic models for each individual drug were joint longitudinal and survival models with time-varying substance use and adjustment for demographics, follow-up time, cohort entry year, and other concomitant drugs including alcohol and binge alcohol. These longitudinal models account for repeated measures and differential loss to follow-up (unbalanced panels).

Analyses (mean follow-up of 3.9 years) included approximately 12,000 people living with HIV with a mean age if 44 and of whom 47% were white. Marijuana was widely used at baseline, though methamphetamine was also common. Relative to non-decreasing use, abstinence was associated with an increase in odds of viral suppression ranging from 42% for marijuana to 118% for opioids (all four substance groups statistically significant). Reduction in use was associated with an increase of 65% for methamphetamine and 172% for opioids. The directionality and statistical significance of these results were maintained in sensitivity analyses with pooled fixed effects meta-analysis using both CNICS and STTR studies.

Ultimately, findings from this large-sample longitudinal analysis suggest that abstinence of all drug groups increases the likelihood of viral suppression and, more interestingly, reducing frequency without abstinence may also increase the likelihood of viral suppression for illicit opioids and methamphetamine. This finding may support the use of medication-assisted treatments (MAT) to reduce substance use, which could have the potential to improve disease-related outcomes for people living with HIV. However, this study did not evaluate why individuals may have increased or decreased use of illicit substances (e.g. MAT, or other treatment programs). In any case, reduction of illicit substance like opioids and meth (even when abstinence is not achieved) seems like a logical target for harm reduction interventions in people living with HIV and likely, in the broader population, to improve overall health outcomes.

One extension of this work would be to evaluate the relative value of programs targeting abstinence and substance use reduction among individuals with HIV compared with other programs. This, of course, requires a true causal relationship between substance use and viral load, which is likely mediated through ART adherence. A simple Markov model could include states for suppressed and not suppressed; however, because suppression reduces the risk of transmission, we might also incorporate shifting dynamics of the population of people living with HIV. Both transmission and individual outcomes were considered in a recent cost-effectiveness analysis of financial incentives for viral suppression authored by CHOICE Alumna Dr. Blythe Adamson and Professors, Dr. Josh Carlson and Dr. Lou Garrison. The main study finding was that paying individuals to take HIV medications was associated with health improvement, reduced transmission, and reduced healthcare costs. While this finding is fascinating, substance use may be an important contextual consideration. One previous study found that financial incentives did not improve viral suppression among substance users and it is unclear how financial incentives may impact drug use and addiction. This is an active area of research and debate. Our study did not look at increases in substance use and viral suppression because we wanted to address the question around reduction and abstinence. Regardless, additional research on strategies to improve viral suppression are needed as well as a better understanding of the interplay between substance use behavior, other risk behaviors, adherence, and viral suppression among people living with HIV.