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
“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
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
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
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
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”.