CATIE News

27 August 2014 

Swiss researchers investigate drug use and its impact on health and survival

As mentioned in the previous CATIE News bulletin, researchers in Switzerland have been studying the impact of drug use on the health and survival of HIV-positive people. Their findings suggest that people who use drugs have a greater chance of unfortunate events and poorer survival compared to people who do not use drugs. If the full benefit of combination anti-HIV therapy (commonly called ART or HAART) is to be extended to more people, then interventions designed to help drug users break free of addiction need to be made available.

Study details

Researchers collected data from 6,529 HIV-positive participants between April 2007 and May 2013.

The average profile of participants when they entered the study was as follows:

  • gender – 69% men, 31% women
  • age – 44 years
  • CD4+ count – 478 cells/mm3
  • 82% were taking ART; of these, 87% had a viral load less than 50 copies/ml
  • current or former smokers – 70%
  • commonly injected street drugs were cocaine (3%) and heroin (2%) 
  • commonly used street drugs that were not injected were marijuana (15%), cocaine (15%), heroin or other opioids (2%), amphetamines (2%)
  • heavy alcohol use – 2%

On average, participants were monitored for about five years.

Results—An important difference

Although overall rates of drug use may seem low, among participants who became HIV-positive from sharing equipment for injecting, rates of drug use were at least twice as great.

Results—Survival

During the study, 334 participants (slightly more than 5%) died.

The risk of death was not increased among people who used to inject drugs or among people who were in a methadone program and also not using street drugs, injected or taken otherwise.

This contrasts with a greater risk of death among people who used to inject drugs but who now took street drugs in other ways, even if they were also in a methadone program. People who had not stopped injecting street drugs were also at increased risk of dying.

Participants who took street drugs were generally at an increased risk for death. Specifically, researchers found that participants who used non-injecting street drugs daily or weekly had a two-fold increased risk for death. Also, weekly or daily use of marijuana was linked to a two-fold increased risk of death. Later in this bulletin we discuss the meaning of this finding with marijuana.

Results—Causes of death

Here are some of the leading causes of death among participants:

  • 25% – cancers unrelated to AIDS
  • 10% – cardiovascular disease
  • 9% – infections unrelated to AIDS
  • 8% – AIDS-related infections
  • 8% – liver disease
  • 6% – suicide

In a large proportion (nearly 20%) of other deaths in this study, researchers were not sure about the cause of death, as some participants died outside of a major hospital or clinic.

Disconnected

Overall, about 11% of participants stopped attending HIV clinic appointments. Among participants who injected street drugs, about 30% stopped attending clinic appointments.

Issues with ART

At the start of the study, the distribution of participants exposed to ART was as follows:

  • 10% of participants had never used ART
  • 81% of participants were taking ART
  • 9% of participants interrupted ART

However, over the course of the study, rates of ART use had increased. Researchers noted that nearly 100% of participants who were supposed to be receiving ART according to local treatment guidelines were doing so by the end of the study.

Researchers found that the risk of treatment interruption, loss of contact with hospital clinics and changes to treatment regimens were greatest among participants who were currently engaged in injecting street drugs or who had injected previously.

Depression

Mental health and emotional issues likely underpin drug use and addiction. Not surprisingly, the likelihood of participants who disclosed to their healthcare providers that they felt depressed was relatively high among people who took street drugs in ways other than by injection (16%) compared to people who did not disclose any substance use (10%).

Among people who injected street drugs, rates of depression were even higher, ranging between 16% and 26%. Furthermore, in this population, the researchers found that “rates of depression were particularly high among [participants who were in a methadone program or who were currently injecting street drugs].”

Contributors to poor survival

Researchers were not able to extract from their data the precise role that non-injecting drug use played in the demise of some participants. Specifically, they were unable to separate the biological effects of drug use from related behavioural and structural factors (access to stable housing, food and employment) or any combination of these factors. Below are several factors linked to poorer health and reduced survival in the present Swiss study that we briefly explore:

Depression

Researchers suspected that factors such as depression probably played a role in reducing adherence to ART, in treatment interruptions and in changing regimens. All of these impacts of depression could ultimately have affected the survival of people who engaged in drug use.

Smoking

The researchers stated that rates of current or past tobacco smoking were “remarkably high” among all participants but particularly high among people who became HIV positive from sharing drug injecting equipment. For example, among the entire study population, 70% of participants were past or current smokers. In contrast, among participants who used to or who currently injected street drugs, rates of smoking were greater than 95%. Smoking tobacco increases the risk for a range of health problems, including cardiovascular disease, lung disease, diabetes and cancers that affect different organ systems.

Liver injury

If left untreated, hepatitis C virus can injure increasing proportions of the liver and heighten the risk for liver cancer. Among people who were injecting street drugs or who had a history of doing so in the present study, researchers found “a substantially higher proportion of liver-associated deaths as a consequence of hepatitis virus co-infection.”

Drug-related deaths

Researchers stated that a “substantial number" of drug-related deaths occurred among people who formerly injected street drugs but who now used other routes of administering such drugs. Researchers were unable to find out if these drug-related deaths were due to overdoses or harmful interactions between street drugs and prescribed medicines.

Marijuana

Historically, HIV-positive adults have used marijuana to mainly relieve nausea and to increase appetite and weight. These issues can arise because of drug side effects; unintentional weight loss can be a consequence of HIV infection.

In the present study, the finding of an association between weekly or daily marijuana use and an increased risk of death is intriguing. However, note that the present study was observational in nature. Such studies are good at finding associations; however, observational studies have built-in limitations due to their design that prevent them from drawing firm conclusions about cause and effect. In this case, the Swiss study could not prove that daily or weekly use of marijuana was indeed a cause of death. It is possible that the association with marijuana arose for this reason: Some participants who used other street drugs and who were already at an elevated risk of death from substance use or its consequences also used marijuana.

Other researchers in South Africa who have reviewed the effect of marijuana on the overall health of HIV-positive people have found that the available published evidence is not sufficiently robust to draw firm conclusions.

Researchers in Vancouver have assessed the impact of high-intensity marijuana use among 523 HIV-positive ART users and found that this street drug did not affect the ability to take ART every day exactly as directed.

Robustly designed long-term clinical trials with marijuana are needed to better define potential benefits and side effects.

Similarities

The finding of the Swiss study—that HIV-positive people who use drugs, particularly people who inject drugs, are at increased risk for death—is not surprising. It has also been found in studies of HIV-negative people who inject drugs. In a recent analysis of nearly 50,000 HIV-positive participants (the DAD cohort) from Australia, the European Union and the U.S., researchers found that people who injected street drugs had approximately double the risk of death compared to gay and bisexual men who did not inject drugs; and triple the risk of death of heterosexual people who did not inject drugs.

What is needed

Based on their findings, the Swiss researchers stated that “comprehensive HIV care needs to incorporate interdisciplinary strategies to integrate prevention and treatment of [injecting and non-injecting drug use as well as smoking tobacco],” as these are all factors that impair survival which can be changed.

A snapshot of Canadian research

Scientists in Canada, particularly in British Columbia, have established links to communities of people who inject drugs, some of whom are HIV positive. As a result, Canada has an enormous body of research on addition and drug-related issues. Below are results from just a few Canadian studies:

Adherence – In a study with more than 400 participants, researchers found that, overall, people who inject drugs are just as able to take ART as people who do not inject drugs and as a result can achieve improved health. However, among participants who injected drugs publicly, adherence to ART was not optimal.

Depression – In one study of nearly 2,000 participants, researchers found that people who overdose tended to have depression. Furthermore, among women with few friends and therefore little social support, overdoses were likely to be fatal. Depression is relatively common among people who use drugs. Helping them to receive screening and treatment for depression is therefore likely to relieve distress and provides an opportunity for healthcare providers to discuss recovery from addiction.

Hunger – In a study with 1,053 participants who used drugs, 65% disclosed being hungry and not being able to afford sufficient food. Not surprisingly, hungry people in this study were also likely to have unstable housing and to experience depression. The researchers recommended improving access to food and social services, including addiction treatment programs.

Opioid substitution therapy and supportive housing – Substituting prescribed methadone or buprenorphine (these are called opioid substitution therapy) for some street drugs can help people recover from addiction. In one study of 545 HIV-positive participants, researchers found that those who were in a methadone treatment program or who were in supportive housing were more likely to be adherent to ART. The researchers recommended that these two factors (methadone programs and supportive housing) be considered as part of strategies to improve adherence to ART.

These are just a few issues that if properly addressed are likely to help people break free from addiction and begin to experience the many benefits of ART.

—Sean R. Hosein

REFERENCES:

  1. Weber R, Huber M, Battegay M, et al. Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study. HIV Medicine. 2014; in press.
  2. Slawson G, Milloy MJ, Balneaves L, et al. High-intensity cannabis use and adherence to antiretroviral therapy among people who use illicit drugs in a Canadian setting. AIDS and Behavior. 2014; in press.
  3. Lutge EE, Gray A, Siegfried N. The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS. The Cochrane Database of Systematic Reviews. 2013 Apr 30;4:CD005175.
  4. Anema A, Kerr T, Milloy MJ, et al. Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting. Substance Abuse Treatment, Prevention, and Policy. 2010 Aug 26;5:20.
  5. Kerr T, Marshall BD, Milloy MJ, et al. Patterns of heroin and cocaine injection and plasma HIV-1 RNA suppression among a long-term cohort of injection drug users. Drug and Alcohol Dependence. 2012 Jul 1;124(1-2):108-12.
  6. Pabayo R, Alcantara C, Kawachi I, et al. The role of depression and social support in non-fatal drug overdose among a cohort of injection drug users in a Canadian setting. Drug and Alcohol Dependence. 2013 Oct 1;132(3):603-9.
  7. Palepu A, Milloy MJ, Kerr T, et al. Homelessness and adherence to antiretroviral therapy among a cohort of HIV-infected injection drug users. Journal of Urban Health. 2011 Jun;88(3):545-55.
  8. Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8.
  9. Volkow ND, Baler RD, Compton WM, et al. Adverse health effects of marijuana use. New England Journal of Medicine. 2014 Jun 5;370(23):2219-27.
  10. Bostwick JM, Reisfield GM, DuPont RL. Clinical decisions. Medicinal use of marijuana. New England Journal of Medicine. 2013 Feb 28;368(9):866-8.
  11. El-Guebaly N. The meanings of recovery from addiction: evolution and promises. Journal of Addiction Medicine. 2012 Mar;6(1):1-9.
  12. Gradin VB, Baldacchino A, Balfour D, et al. Abnormal brain activity during a reward and loss task in opiate-dependent patients receiving methadone maintenance therapy. Neuropsychopharmacology. 2014 Mar;39(4):885-94.
  13. Veldhuizen S, Callaghan RC. Cause-specific mortality among people previously hospitalized with opioid-related conditions: a retrospective cohort study. Annals of Epidemiology. 2014 Aug;24(8):620-4.
  14. Mackesy-Amiti ME, Donenberg GR, Ouellet LJ. Psychiatric correlates of injection risk behavior among young people who inject drugs. Psychology of Addictive Behaviors. 2014; in press.
  15. Stein MD, Anderson BJ, Thurmond P, et al. Comparing the life concerns of prescription opioid and heroin users. Journal of Substance Abuse Treatment. 2014; in press.