Undetectable viral load reduces the risk of HIV-associated anal cancer

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HIV therapy that effectively controls viral load reduces the risk of anal cancer, US research published in the online edition of the Journal of Acquired Immune Deficiency Syndromes shows. The retrospective study involved almost 29,000 men taking combination antiretroviral therapy. Men with viral suppression for at least 60% of the time while taking treatment were about 50% less likely to develop anal cancer than men with poor virological control.

“Our study now provides evidence that suppressing HIV viral load through effective cART [combination antiretroviral therapy] nearly halves the risk of SCCA [squamous cell cancer of the anus] compared to individuals with poor HIV viral load control”, write the authors. “Ensuring undetectable viral load control ensuring effective cART utilization may be an important aspect of SCCA prevention among HIV-infected individuals.”

Starting antiretroviral therapy at a higher CD4 cell count was also associated with a significant reduction in the risk of anal cancer.

Glossary

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

strain

A variant characterised by a specific genotype.

 

Rates of anal cancer are much higher in people with HIV than the general population. Although the cancer remains rare among people with HIV, several studies have shown that its incidence has increased since effective combination antiretroviral therapy became available. This is likely to be because people with pre-cancerous cell changes associated with high-risk strains of human papillomavirus (HPV) are living long enough for the cancer to develop.

Investigators from the US Department of Veterans Affairs wanted to see if an undetectable viral load during HIV therapy reduced the risk of anal cancer.

They therefore designed a retrospective study involving male patients who received care between 1985 to 2009. The investigators first compared the incidence of anal cancer between men who had taken HIV therapy and those who had never taken combinations of antiretroviral drugs. Analysis was then restricted to individuals with experience of combination HIV treatment to see which factors were associated with the risk of anal cancer.

A total of 45,231 men were included in the analysis. They provided a total of 307,495 person years of follow-up, and there were 377 cases of anal cancer.

Overall incidence of the cancer was 134 cases per 100,000 person years. It did not differ significantly between men with experience of combination antiretroviral therapy and those who were treatment-naive (147 vs 134 cases per 100,000 person years).

Approximately 29,000 men (63%) had received HIV therapy, and 302 of these individuals were diagnosed with anal cancer.

The first set of analysis showed that white men had a higher risk of the cancer compared to black men (p < 0.0001) and Hispanic men (p = 0.0009). Men with a higher CD4 cell count (500 cells/mm3 or above) had a lower risk of anal cancer compared to men with immune suppression (200 cells/mm3 or below, p < 0.0001). Having a higher nadir (lowest ever) CD4 cell count also reduced the risk of anal cancer (500 vs 200 cells/mm3, p = 0.0005).

Viral load during HIV therapy was also an important risk factor. Men with an undetectable viral load between 61 and 80% of the time, and those with an undetectable viral load between 81 and 100% of the time were less likely to develop the cancer (p = 0.001; p < 0.001) than men with ongoing HIV replication.

The investigators then performed another set of analysis, this time controlling for factors such as current CD4 cell count.

This confirmed that men with a viral load between 61 and 80% of the time (p = 0.004) and those with an undetectable viral load between 81 and 100% of the time (p = 0.0004) had a decreased risk of anal cancer. In each case the risk was approximately 50% lower compared to men whose viral load was undetectable for 20% of the time.

“This is the first large cohort study to demonstrate that maintaining undetectable viral load independently decreases the incidence of SCCA above and beyond other known SCCA risk factors,” comment the authors.

Men with a nadir CD4 cell count below 200 cells/mm3 had a higher risk of anal cancer compared to those with nadir CD4 cell counts between 200 to 350 cells/mm3 (p < 0.0001), and  also men with a nadir CD4 cell count above 350 cells/mm3 (p < 0.0001).

The authors acknowledge that the findings are limited by the retrospective design of the study. They also note that they were unable to supply data regarding gay men, the group of people living with HIV who have the highest rates of anal cancer.

Despite this, they believe their results provide “support for initiating cART at higher CD4 cell counts and maintaining suppressed HIV viral loads”.

References

Chiao EY et al. The impact of HIV viral control on the incidence of HIV-associated anal cancer. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0b013e3182968fa7, 2013.