Early Antiretroviral Treatment Reduces New HIV Infections, Says British Columbia Study

		SUMMARY: A study published in the July 18, 2010 advance online edition of the Lancet (free full text with registration) and discussed at the XVIII International AIDS Conference (AIDS 2010) this week in Vienna offers further evidence that widespread early antiretroviral therapy (ART) can reduce the spread of HIV at a population level. Universal early ART is not without controversy, however, due to concerns about side effects, drug resistance, and resource allocation.

Effective combination ART reduces HIV viral load to a very low or undetectable level and thereby dramatically decreases the likelihood of HIV transmission on an individual level.

Mathematical models developed over the past fefw years have suggested that expanded use of ART sooner after HIV diagnosis could lower HIV incidence within a population. A World Health Organization (WHO) model published in January 2009 found that HIV transmission could potentially be eliminated if universal testing were implemented and all people who test positive received prompt treatment.

More recently, Julio Montaner from the British Columbia Centre for Excellence in HIV/AIDS and colleagues last month reported findings from a model indicating that if all people with HIV in Vancouver were treated according to International AIDS Soceity-USA guidelines then in effect, the rate of new infections would decrease by almost half.

Now, the British Columbia researchers have shown that the outcomes predicted by modelling appear to be occurring in real life.

Montaner's group sought to estimate the association between plasma HIV viral load, highly active antiretroviral therapy (HAART) coverage, and number of newly identified HIV cases in the province of British Columbia. The epidemic there is concentrated in Vancouver and largely driven by injection drug use. Canada provides universal health care, including free HIV treatment, and the province has a centralized health system, making it possible to collect comprehensive data.

The investigators obtained data from the British Columbia Centre for Disease Control about the number of HIV tests performed and the number of people newly diagnosed. They also collected information about viral load, CD4 cell count, and ART use from population-based registries maintained by the BC Centre for Excellence in HIV/AIDS.

They then constructed linear regression models to estimate the association between new HIV diagnoses and viral load, calendar year, and number of individuals taking combination therapy.

Results

	Between 1996 and 2009, the number of individuals currently receiving combination ART increased from 837 to 5413, a significant increase of 547%.
	During the same period, the number of new HIV diagnoses fell from 702 to 338 per year, a 52% decrease.
	The overall correlation between the number of people on ART and the number newly testing HIV positive per year was -0.89, indicating a significant association (P < 0.0001).
	For every 100 additional people on combination ART, the number of new HIV cases decreased by a factor of 0.97, or by 3%.
	For each 1 log decrease in viral load, the number of newly diagnosed HIV cases decreased by a factor of 0.86.

Based on these findings, the study authors wrote, "We have shown a strong population-level association between increasing HAART coverage, decreased viral load, and decreased number of new HIV diagnoses per year."

These results, they added, "support the proposed secondary benefit of HAART used within existing medical guidelines to reduce HIV transmission.

Patterns of ART use during the study period "changed strikingly on the basis of contemporary therapeutic guidelines," the researchers elaborated in their discussion. In particular, there were 2 distinct phases of steady expansion of treatment coverage, separated by a stable period between 2000 and 2003. Community viral load -- or average viral load across a defined population -- and annual new HIV diagnoses decreased substantially during both phases of HAART expansion, while remaining stable during the intervening steady period.

Further analysis showed that the association between increased HAART coverage, decreased community viral load, and reduction in new HIV diagnoses was largely attributable to injection drug users.

After declining slowly for several years, there was a sharp decrease in new infections among current or former drug users during 2007-2008 -- and the number with undetectable viral load increased by 86% -- after a specific outreach effort was implemented. This is a promising finding since most previous research showing declines in community viral load and HIV incidence have focused on sexual transmission.

These results also offer evidence to refute the stereotype that active drug users are unable to adhere to and benefit from antiretroviral treatment.

In an accompanying Lancet editorial, Franco Maggiolo and Sebastiano Leone from Ospedali Riuniti in Bergamo, Italy, wrote, "While waiting for an effective vaccine, experiences such as those reported today should be strongly considered by clinicians, national and international agencies, policymakers, and all parties involved in the development of treatment guidelines, because the population-based dimension of HAART might play an important part in the future control of the HIV epidemic."

Investigator affiliations: British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, Vancouver, BC, Canada; Division of AIDS, University of British Columbia, Vancouver, BC, Canada; Department of Psychiatry, University of California, San Diego, CA; Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; Vancouver Coastal Health Authority, Vancouver, BC, Canada; Office of the Provincial Health Officer, Ministry of Healthy Living and Sport, Government of British Columbia, Victoria, BC, Canada.

7/23/10

References

JS Montaner, VD Lima, R Barrios, and others. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet (Free full text with registration). July 18, 2010 (Epub ahead of print).

Franco Maggiolo and Sebastiano Leone. Is HAART modifying the HIV epidemic? Lancet. July 18, 2010 (Epub ahead of print).