Tentative evidence of treatment-as-prevention efficacy in northern France

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Physicians at seven HIV clinics in north-eastern France have provided evidence of an association between a decrease in the so-called 'community viral load' (CVL) in diagnosed patients between 2005 and 2010 and the number of new diagnoses of HIV.

However, the association is weaker than expected, and the study has been taken into account by the country’s health ministry as part of the evidence suggesting the necessity of expanding HIV screening.

The decline in CVL, and the correlation between it and a decline in new diagnoses in any one year, were both statistically significant. The decline in the number of new diagnoses over the five years, on the other hand, was not statistically significant in itself. The researchers comment that the effect observed is unlikely to be due to chance, but that more people with HIV would need to be diagnosed and put on treatment to make a large difference to infections.

The study

Between 2005 and 2010 seven clinics in the towns of Nancy, Reims, Tourcoing, Besançon, Strasbourg, Amiens and Dijon collected 24,747 patient-years of data on viral load and CD4 count. This represented 60% of the diagnosed people with HIV in the area, which covers five of France’s 22 administrative regions. The number of people providing data increased every year – from 3573 in 2005 to 4631 in 2010. Almost exactly the same number of people had acquired HIV via gay and via heterosexual sex (42% each), 6% acquired HIV through injecting drugs, and the other 10% via other or unknown routes.

Glossary

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

log

Short for logarithm, a scale of measurement often used when describing viral load. A one log change is a ten-fold change, such as from 100 to 10. A two-log change is a one hundred-fold change, such as from 1,000 to 10.

The average CD4 count at diagnosis increased from 395 cells/mm3 in 2005 to 404 cells/mm3 in 2010. Although this increase was slight, it was statistically significant (p=<0.001). The proportion of patients who had been on antiretroviral therapy (ART) for at least three months at the time their viral load was measured rose from 70% in 2005 to 85% in 2010, representing a 57% increase in the number of people on ART over the five years.

'Community viral load' was defined as the sum of the viral load values from the most recent test in each person in any one year, with 100 copies/ml as the lowest value, as this was the highest criterion for undetectability. This total declined from 79.5 million (7.90 log) in 2005 to 57.5 million (7.76 log) in 2010, and this decline was significant (p=0.005).

Diagnoses declined from 256 in 2005 to 246 in 2010 but this small decrease disguises a peak of 265 cases in 2006 and a trough of 233 in 2008. Although there was no significant decline in diagnoses (p=0.067) there was a significant correlation between the year-on-year decrease in CVL in any one year and the decline in diagnoses for that same year (p=0.01).

The researchers comment that the association between community viral load and diagnoses was probably only “moderate” because this part of the country represents France’s industrial heartland, with wide ethnic diversity, pockets of deprivation, and many individuals being infected outside the area.

The decline in CVL was a modest 28%, despite a nearly 60% increase in the absolute number of people on ART in the five years. This is probably, the researchers comment, because many infections are arising from the estimated 30% of people with HIV in France who are undiagnosed. Without taking the viral load of these invisible individuals into account, a true estimate of any correlation between the proportion undetectable on ART and the annual number of diagnoses cannot be made, the researchers comment.

As is the case with many other countries, France’s latest national plan for HIV recommends an expansion of HIV screening, partly because of the very modest effect seen in this study, which was included in the evidence used to write the latest plan.

References

Henard S et al. Is total community viral load a robust predictive marker of the efficacy of the TasP strategy? JAIDS, e-publication ahead of print, doi: 10.1097/QAI.0b013e318263a111, 2012.