An intervention designed to facilitate treatment for HIV and substance use was associated with a 50% reduction in mortality for people living with HIV who inject illicit drugs, a study has found. In addition, the people who received the intervention were nearly twice as likely to report being in treatment for HIV and substance use after one year as those who received their national standard of care. They also were about twice as likely to have suppressed their HIV to undetectable levels after one year.
The intervention consisted of psychosocial counselling along with guidance and support navigating the healthcare system.
People who inject drugs often have high rates of HIV infection, poor access to and use of treatment for HIV and substance use, and high mortality in the US and globally. Needle sharing among people who inject drugs is the main route of HIV transmission in some parts of the world.
"People living with HIV who inject drugs often encounter multiple obstacles to beginning and adhering to treatment for HIV infection and substance use," said Dr Anthony S Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. "This study demonstrates that providing guidance and counselling can help such individuals overcome barriers to starting and staying in care and treatment, leading to a significantly higher rate of HIV suppression and a much lower rate of death."
NIAID co-funded the study with the National Institute on Drug Abuse (NIDA), also part of NIH. The NIH-funded HIV Prevention Trials Network (HPTN) implemented the trial, called HPTN 074.
"People who inject drugs and are living with HIV have potentially fatal co-occurring conditions, yet they and their at-risk partners often face different and confusing care delivery systems," said NIDA director Dr Nora D Volkow. "This study shows that integrated interventions, including help from systems navigators, can dramatically reduce mortality for both conditions."
None of the few new HIV infections in the trial occurred among the injection partners of people living with HIV who received the study intervention. Scientists could not draw a firm conclusion about the impact of the intervention on HIV transmission through injection drug use, however, because the study was not statistically powered to measure that effect.
HPTN 074 took place in three countries with HIV epidemics driven by injection drug use: Indonesia, Ukraine and Vietnam. The study team enrolled 502 men and women ages 18-60 years who are living with HIV and inject drugs, and 806 HIV-uninfected men and women who inject drugs with them (injection partners). At least one injection partner of every person in the study living with HIV enrolled. The people living with HIV were assigned at random to receive either the national standard of care for HIV infection and substance use or the standard of care plus an integrated and flexible intervention designed to facilitate treatment. The study participants were followed for one to two years.
Study participants assigned to receive the intervention were immediately referred to local health-care providers for anti-HIV therapy to treat their infection, prevent sexual transmission of HIV, and potentially prevent HIV transmission via needle sharing. In addition, each participant who received the study intervention was assigned a systems navigator who helped the participant identify and overcome structural barriers to starting and staying in care and treatment for HIV and substance use. Such barriers could include unfamiliarity with how to enrol in medical care for HIV or difficulty keeping treatment-related appointments. Finally, psychosocial counsellors helped each study participant overcome their unique psychological obstacles to starting and staying in treatment, such as lack of interest in therapy, difficulty establishing a medication-taking routine, or stigma.
In addition, all study participants, including the HIV-uninfected injection partners, received their country's standard of care for people who inject drugs. This typically included referral for treatment of substance use; referral to needle/syringe exchange programs, if legal and available; injection risk reduction counselling; sexual risk reduction counselling; HIV counselling and testing; and referral for diagnosis and treatment of sexually transmitted infections, hepatitis B and C viruses, and tuberculosis, as appropriate. Those study participants living with HIV who received only the standard of care also were referred to local health-care providers for anti-HIV therapy according to national guidelines for when to start treatment.
At the end of the study, 15% of participants with HIV who had received the standard of care had died, compared to 7% of participants with HIV who had received the intervention, corresponding to a 53% reduction in mortality.
Some 26% of deaths among study participants who had HIV were considered clearly HIV-related, and 3% were due to drug overdose. Among the 42% of deaths with unknown cause, 24% occurred among people whose immune systems were in poor health. Non-HIV-related medical events caused 21% of deaths overall, and trauma and suicide accounted for the remaining eight percent.
After one year, 41% of study participants who received the intervention had undetectable levels of HIV in their blood, compared to 24% of participants who received only the standard of care. Also, 72% of study participants who received the intervention reported being in treatment for HIV at the end of one year, compared to 43% of those who received only the standard of care – 41% of study participants who received the intervention reported being in treatment for substance use at the end of one year, compared to 25% of those who received only the standard of care.
"The intervention in this study had a remarkably positive impact on people living with HIV who inject drugs," said protocol chair Dr William C Miller. "It was designed to be scalable to other settings, and we hope that it can help this important population worldwide." Miller is professor and chair of the division of epidemiology at The Ohio State University College of Public Health in Columbus.
Previous studies have demonstrated that when a person takes anti-HIV medication that suppresses the amount of virus in the blood to undetectable levels, it both protects the health of the individual and prevents sexual transmission of the virus. Whether viral suppression also prevents HIV transmission through needle sharing with injection partners remains unknown.
The HPTN 074 study was not designed to determine whether the intervention would reduce the rate of HIV infection among injection partners of the participants living with HIV, but rather to determine the feasibility of a larger study that could measure this effect.
In HPTN 074, seven injection partners of participants living with HIV who received only the standard of care became infected, while no injection partners of participants living with HIV who received the study intervention became infected. This result is promising, according to the investigators, but because the overall HIV incidence among injection partners was so low, a larger clinical trial to test the effect of the study intervention on HIV transmission among injection drug users would not be feasible.
Given the success of the study intervention at reducing mortality and increasing the rates of both participation in treatment and viral suppression, investigators have offered the intervention to all the HPTN 074 study participants living with HIV. In addition, all participants living with HIV are being followed for a second year to determine whether the positive effects of the intervention are maintained.
Background: People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use.
Methods: This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18–45 years (updated to 18–60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer-generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12–24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov,NCT02935296, and is active but not recruiting new participants.
Findings: Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4–1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3–2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3–2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0–1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4–2·1; incidence rate difference −1·0 per 100 person-years, 95% CI −2·1 to 1·1). No severe adverse events due to the intervention were recorded.
Interpretation: This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered.
William C Miller, Irving F Hoffman, Brett S Hanscom, Tran V Ha, Kostyantyn Dumchev, Zubairi Djoerban, Scott M Rose, Carl A Latkin, David S Metzger, Kathryn E Lancaster, Vivian F Go, Sergii Dvoriak, Katie R Mollan, Sarah A Reifeis, Estelle M Piwowar-Manning, Paul Richardson, Michael G Hudgens, Erica L Hamilton, Jeremy Sugarman, Susan H Eshleman, Hepa Susami, Viet Anh Chu, Samsuridjal Djauzi, Tetiana Kiriazova, Duong D Bui, Steffanie A Strathdee, David N Burns
[link url="https://www.niaid.nih.gov/news-events/novel-intervention-halves-rate-death-among-people-living-hiv-who-inject-drugs"]NIAID/NIH material[/link]
[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31487-9/fulltext"]The Lancet abstract summary[/link]