Canadian researchers have published a large cohort study indicating that higher uptake of antiretroviral therapy might reduce HIV transmission considerably in some populations.
While there is widespread recognition that limiting HIV replication by taking ART makes HIV-positive people less infectious, evidence is still limited regrading the population-level HIV prevention impact of expanding ART coverage.
The Canadian team set out to assess the epidemiological dynamics of treatment and prevention by conducting a province-wide analysis of trends in antiretroviral usage, viral load levels and new HIV diagnoses in British Columbia from 1996 to 2009. They found notable associations between these three variables, and also found that ART usage among injecting drug users (IDUs) greatly influenced outcomes.
In their paper in the August 14, 2010 edition of The Lancet, the researchers refined conclusions announced at a conference in early 2010. The paper reports that during two periods of expanding ART coverage in British Columbia, new HIV infections declined by 40% in the period between 1996 and 1999, and then by 23% in the period 2004-2009.
In contrast the number of new diagnoses remianed stable during the period 2000-2003 when scepticism about early treatment was at its height and many patients previously taking treatment chose to interrupt treatment.
Study findings were grouped into three distinct ART treatment eras: 1996 to 1999, when the scale-up following the discovery of the first highly effective ART regimens was underway; 2000 to 2003, when the popularity of treatment interruptions led to a leveling-off of ART usage; and 2004 to 2009, when treatment interruptions became less common as a result of widespread agreement that they caused poorer long-term health outcomes.
During the first period, 1996 to 1999, the number of British Columbia residents receiving ART increased 258%, from 837 to 2994 (p=0.021). In the same period, annual diagnoses of new HIV cases dropped 40%, from 702 to 416 (p=0.003).
Between 2000 and 2003, there were only slight changes in both the number of people receiving ART and the number of people diagnosed with HIV.
More widespread use of ART was associated with a second major decline in new HIV cases from 2004 to 2009. The number of people taking ART rose from 3585 in 2004 to 5413 in 2009, a 51% increase (p<0.0001). Meanwhile, the number of annual HIV cases dropped 23%, from 441 to 338 (p<0.0001).
ART is available for free to all residents of British Columbia.
Information about injecting drug use among cohort members was available from 1999 onward. When researchers stratified data according to history of injecting drug use, they found different trends among IDUs and non-IDUs. The number of new HIV cases among IDUs decreased about 50% from 1999 to 2009, while the number of new HIV cases among non-IDUs remained about the same.
Viral load trends were found to be congruent with these findings.
In the full cohort, the proportion of people with plasma HIV RNA levels below 500 copies/mLincreased from less than 10% in 1996 to more than 50% in 2009 (p<0.0001). Between 2004 and 2009, the proportion of non-IDUs with plasma HIV RNA levels below 500 copies/mL increased by 36% (p<0.0002), while the proportion of IDUs with viral loads below that threshold increased by 82% (p=0.001).
Similar trends were observed in the proportions of non-IDUs and IDUs with viral load levels below 50 copies/mL.
Study data came from the British Columbia Centre for Disease Control and the British Columbia Centre for Excellence in HIV/AIDS, which maintain records on the vast majority of people undergoing HIV testing and seeking HIV-related medical care in the province.
New HIV diagnoses were used as a surrogate for new HIV infections in this study.
Researchers considered whether the observed declines in new HIV diagnoses might have resulted from fewer HIV tests being performed, but they found that testing in British Columbia actually increased during the study years. They note that when the numbers tested for HIV have increased in other studies, this has been associated with an increase in HIV diagnoses.
Researchers rejected the possibility that declines might reflect changes in sexual behaviour, pointing to the fact that increasingly more cases of sexually transmitted syphilis, gonorrhoea and chlamydia had been reported from 1996 to 2008.
The paper acknowledges that while there were clear associations between ART coverage, new HIV diagnoses and viral load levels, the design of the study makes it impossible to definitively attribute these findings to cause-and-effect relationships.
Still, it notes, “Ample supportive evidence exists regarding the preventive effect of [ART] on HIV transmission, derived from vertical transmission studies and from cohort studies of serodiscordant couples, IDU cohorts and population-based studies.”
Interest in the population-level impact of “treatment as prevention” has increased in recent months, partly because of debate about the conclusions that a team of World Health Organization researchers has drawn from mathematical modeling. In a late 2008 Lancet article, they proposed that universal HIV testing and immediate treatment for all HIV-positive people in the worst-off countries could greatly slow the spread of the epidemic.
Other researchers have criticised the WHO analysis, and a UK team recently published a modelling exercise that takes different factors into account. The team concluded that the impact of treating more HIV-positive people would vary in accordance with HIV risk behavior in different settings.
Montaner JSG et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet 376: 532 – 539, 2010. (Link to full text publication - may require registration and subscription)