Over the past decade, evidence has been accumulating that starting potent combination anti-HIV therapy (commonly called ART) as early as possible in the course of HIV disease is beneficial. The evidence trend culminated in the summer of 2015 with the release of the results from the START clinical trial. In that large well-designed study, researchers were able to prove that starting ART early resulted in measureable benefit. Specifically, early initiation of ART reduced the risk of developing serious illness or death.
By initiating ART and taking it every day exactly as directed, the amount of HIV in a person’s blood eventually falls to very low levels (below a threshold at which it can be accurately counted). Once this happens, by keeping HIV at such a low level by continuing to use ART, a person’s risk of spreading HIV becomes extremely unlikely.
Given the health and prevention benefits of early ART, it is important to diagnose HIV infection as soon as possible and help get people into care. Using a database called CANOC, researchers at the B.C. Centre for Excellence in HIV/AIDS as well as other researchers across Canada collaborated in an analysis that sought to explore when in the course of HIV disease patients in Canada initiated ART. They found that in the year 2000, the average CD4+ cell count at which ART was initiated was 190 cells/mm3. By the end of the year 2012, the average starting point for ART had risen to 360 cells/mm3. Although in a broad sense this trend is moving in the right direction, over the course of the study, researchers found that nearly half of participants delayed initiating ART until their CD4+ count was less than 200 cells/mm3 or until they had an AIDS-related illness.
Study details
For this analysis the researchers made use of data accumulated by Canada’s national HIV observational database, called CANOC. This database collects health-related information from HIV-positive people from major clinics. The clinics remove any information that could be used to identify people from the data before it is sent to CANOC.
The researchers focused on data collected from three large provinces—British Columbia, Ontario and Québec—with a total of 8,942 participants. At the time they entered the study, their average profile was as follows:
- age – 40 years
- 82% men, 18% women
- CD4+ count – 220 cells/mm3
- viral load – 80,000 copies/mL
Results
In the year 2000, the average CD4+ count at which a person started ART was 190 cells/mm3. By the end of 2012, the starting point had moved to 360 cells/mm3.
Over the course of the study, researchers found that 48% of participants delayed initiating ART until their CD4+ count was less than 200 cells/mm3 or until they had an AIDS-related illness.
Focus on the last year
Researchers found that in 2012, the last year of the study, the people who had the highest CD4+ counts when initiating ART were from Québec (at 400 CD4+ cells/mm3), followed by B.C. (at 360 cells/mm3), followed by Ontario (at 329 cells/mm3).
The researchers analysed data from the final year of the study and found that 664 people initiated ART. Nearly half (48%) of these people delayed initiating ART until their CD4+ count was less than 350/mm3 cells or until they had an AIDS-related illness.
Who tends to initiate ART late?
In analysing data from the latter years of the study (2008 to the end of 2012), researchers found that late initiation of ART (starting when the cell count was less than 350 cells/mm3) was most likely in the following populations:
- women
- heterosexuals
- older people
- participants from Ontario
Bear in mind
It is possible that some of the conclusions drawn by the researchers may have inadvertently been biased because in Ontario and Québec participant data came only from selected HIV clinics, mostly in urban regions. However, most HIV-positive people in these two provinces live in such regions. Also, the researchers stated: “Significant improvements [in care and treatment] were documented in [all three provinces] over the study period.”
Moving forward
Ever since the first anti-HIV drug became available in the late 1980s there has been debate over the best point in the course of HIV disease at which to begin therapy. In the ensuing decades, the starting point for ART has moved back and forth, between early and late initiation. This was mainly due to the toxicity of first- and some second-generation treatments.
However, in the past 10 years the starting point for ART began to move only in one direction—earlier therapy—as the evidence for the benefits of this became overwhelming. Therapies for the initial treatment of HIV are now much safer and simpler than what was available 16 years ago. There are even entire regimens that can be taken in just one pill once daily. Leading HIV treatment guidelines and recommendations from international scientific organizations now recommend that ART be initiated as early as possible in the course of HIV infection.
Implications for Canada
The study authors encourage policy planners, health departments and ministries to consider making HIV testing more widely available. This is because the sooner a person knows their infection status, the sooner they can begin ART and preserve their immune system. The researchers would like to see HIV testing offered to people whom doctors and nurses might not usually consider at risk for HIV. For this to happen, they call for making the offer of an HIV test a routine event in hospitals and primary care centres. Furthermore, they would like to see a publicity campaign to encourage people to get tested.
Publicizing and broadening access to HIV testing is important because the Public Health Agency of Canada estimates that about 21% of people who have HIV today do not know their infection status. For comparison, the equivalent figures for three other high-income countries are as follows:
- France – 19%
- UK – 17%
- U.S. – 13%
The researchers also call for the development of “Canadian consensus guidelines…as a useful next step to provide uniform, evidence-based clinical directives for HIV management across Canada.”
Such guidelines, the researchers stated, should be based on the goals of the Joint United Nations Programme on HIV/AIDS (UNAIDS), which are simplified into the phrase “90-90-90.” This phrase summarizes key milestones that countries are encouraged to aspire to and achieve by the year 2020, as follows:
- 90% of people with HIV know their infection status
- 90% of people diagnosed with HIV are taking ART
- 90% of people taking ART have a viral load that is "undetectable" (generally less than 50 or 40 copies/mL in their blood).
As more of Canada’s provinces and territories move toward these outcomes, having a national public health strategy to improve engagement in care can help ensure that progress in reducing new HIV infections an dimproved health outcomes occur evenly across the country.
Since the study on initiation of ART was done, the CANOC database has accumulated data on about 10,300 HIV-positive patients. It would be useful if in a few years researchers repeat their analysis to see at what CD4+ counts people are initiating ART.
Resources
Detailed results from the START study – TreatmentUpdate 210
Changing the Narrative: Why HIV prevention work in Canada needs to embrace HIV treatment – Prevention in Focus
The Canadian HIV Observational Cohort (CANOC)
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents – U.S. Department of Health and Human Services
—Sean R. Hosein
REFERENCES:
- Cescon A, Patterson S, Davey C, et al. Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care. Journal of the International AIDS Society. 2015 Oct 5;18:20024.
- Supervie V, Lacombe JM, Marty L, et al. How far are we from early cART for all? A nationwide population-based study in France. Conference on Retroviruses and Opportunistic Infections, 22-25 February 2016, Boston, MA. Abstract 1043.
- Skingsley A, Yin Z, Kirwan P, et al. HIV in the UK—Situation report 2015: data to end 2014. November 2015. Public Health England, London.
- HIV in the United States: At a glance. Centers for Disease Control and Prevention. 29 September 2015.
- Sullivan PS, Jones JS, Baral SD. The global north: HIV epidemiology in high-income countries. Current Opinion in HIV/AIDS. 2014 Mar;9(2):199-205