HIV treatment as prevention scale-up linked to reduced mortality among people who inject drugs in Vancouver

HIV-related and all-cause death decreased significantly among people who inject drugs – with similar declines for both women and men – since the introduction of expanded access to antiretroviral therapy (ART) as part of a 'treatment as prevention' initiative in Vancouver, Canada, researchers reported last month at the Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. These findings support recommendations to treat everyone with HIV, both to benefit their own health and to reduce transmission.

Early HIV treatment and biomedical prevention were key themes of the IAS conference. Data from the START trial showed that starting ART immediately after HIV diagnosis, rather than waiting for the CD4 cell count to drop, was associated with a 57% lower risk of AIDS-related and non-AIDS illness and death. Final results from HPTN 052 showed no evidence of transmission from HIV-positive people on ART with full viral suppression to their partners – a concept dubbed treatment as prevention.

Kanna Hayashi of the British Columbia Centre for Excellence in HIV/AIDS reported findings from an analysis of rates and predictors of death among HIV-positive people who inject drugs in Vancouver since the advent of effective combination ART in the late 1990s.

In 2010 the city began an initiative to increase access and improve adherence to ART in an effort to stem the on-going epidemic among drug injectors. HIV/AIDS remains a major cause of death among people who inject drugs, but it is not clear how efforts to expand HIV treatment access have affected mortality in this population, the researchers noted as background.

The study team looked at longitudinal data from ACCESS (AIDS Care Cohort to Evaluate Exposure to Survival Services), a prospective cohort study of nearly 1,000 HIV-positive injection drug users. Every six months participants completed a questionnaire about drug use and other risk factors and were tested for HIV and hepatitis C virus (HCV). These data were confidentially linked to a province-wide ART dispensing database and the British Columbia vital statistics database to determine mortality rates and causes of death between May 1996 and May 2013.

The analysis included 961 participants, of whom 353 (37%) were women. About half were white and the median age was 35 for women and 31 for men. Most participants – 94% of men and 89% of women – were coinfected with HCV.

Participants had been injecting drugs for a median of about 15 years; 39% of women and 19% of men reported daily heroin injection, while 35% and 27%, respectively, reported daily cocaine injection. More than 70% had unstable housing, about a quarter of both men and women had been incarcerated and half the women and 8% of the men reported doing sex work. Nearly a third were enrolled in methadone maintenance therapy and nearly 40% were enrolled in other types of addiction treatment.

Most participants had recently started combination ART; 16% had started treatment with a CD4 cell count above 200 cells/mm³ and had at least 95% adherence, while two-thirds had either started with a lower CD4 count or had poorer adherence, and 16% had never accessed ART.

A total of 264 deaths due to any cause were recorded during the study period. Overall mortality rates were 4.64 per 100 person-years among men and 4.41 per 100 person-years among women. Over the entire study period, the greatest proportion of deaths were HIV-related (44%), followed by overdose (19%), other non-accidental causes (18%), other accidental causes (6%) and liver-related deaths (5%).

HIV-related mortality declined slowly in the late 1990s and early 2000s, but overall mortality remained high. HIV-related deaths decreased significantly for both men and women since 2010, coinciding with the start of the treatment as prevention ART expansion (adjusted rate ratio 0.11 for men and 0.20 for women). Rates of all-cause mortality and deaths due to drug overdose also declined for both men and women during this period.

There was no gender-based difference in age-adjusted all-cause mortality rates. The only significant gender difference was a 10-fold higher rate of liver-related death among men.

In a multivariable survival analysis, people who started ART with a CD4 count above 200 cells/mm³ and had at least 95% adherence during the first year on treatment had a significantly lower risk of death than those who never started ART (adjusted hazard ratio [HR] 0.18 for men and 0.35 for women). Daily illicit use of prescription opioids was independently associated with increased mortality, but only among men (adjusted HR 2.07).

"In this 18-year cohort study of community-recruited HIV-positive people who inject drugs, mortality rates were similar between male and female participants," the researchers concluded. "HIV-related mortality rates have significantly declined since the beginning of efforts to expand access and adherence to ART, suggesting that treatment-as-prevention-based efforts to scale-up ART among people who inject drugs have been associated with sharp declines in HIV/AIDS-related mortality among this population."

However, they added, "High-intensity prescription opioid use independently predicted mortality among men, indicating a need to identify factors shaping harms from illicit prescription opioid use among this population."