HIV therapy that achieves long-term
suppression of viral load and sustained immune reconstitution reduces the risk
of persistent cervical infection with high-risk strains of human papillomavirus
(HPV), research published in the online version of the Journal of Infectious Diseases shows.
Belgian researchers established that an
undetectable viral load and higher CD4 cell count were both associated with reduced
prevalence and incidence of high-risk cervical HPV infection. Suppression of
viral load with antiretroviral therapy for at least 24 months increased the chances
of clearing cervical HPV infection.
‘The risk of HRHPV [high-risk HPV] carriage
decreased in case of sustained immunological reconstitution…and long-lasting
HIV viral suppression,” write the authors. “These results were reproducible and
highly significant whether we considered only the first HRHPV screening or
persistent and cleared infections.”
Cervical cancer is an AIDS-defining
malignancy and rates of cervical infection with cancer-associated high-risk
strains of HPV are elevated in HIV-positive women. Modern antiretroviral
therapy can achieve sustained suppression of viral load and improvements in
immune function. Rates of AIDS-defining illnesses have fallen dramatically and
the prognosis of many HIV-positive people is now excellent. However, the impact of effective HIV therapy
on cervical HPV infection is still unclear.
Investigators in Brussels therefore
designed a prospective study involving 652 HIV-positive women who had regular
cervical screening (smear tests) between 2002 and 2011. They examined the
factors associated with prevalent, incident and persistent high-risk cervical
Most of the women were from sub-Saharan
Africa (84%) and their median age at the time of first HPV screening was 38
years. Median baseline CD4 cell count was 426 cells/mm3, over
three-quarters (79%) were taking HIV therapy and 56% had an undetectable viral
Baseline prevalence of high-risk cervical
HPV infection was 43%. Prevalence decreased significantly with age (30 years =
65% vs over 49 years = 32%; <
0.001). Prevalence also decreased at higher CD4 cell counts (below 200 cells/mm3
= 63% vs 350-499 cells/mm3 = 43% vs above 500 cells/mm3
= 28%; p < 0.001).
Statistical analysis that controlled for
potential confounders showed that a nadir CD4 cell count above 500 cells/mm3
and antiretroviral therapy for two or more years with an undetectable viral
load (p < 0.0001) were both associated with a reduced risk of baseline
high-risk HPV infection.
The participants were followed for a median
of 103 months. Some 54 women with a
negative baseline screen were subsequently infected with a high-risk HPV strain,
providing a cumulative prevalence of 51%.
Screening showed that overall 63 women
cleared the infection and that it persisted in 77 individuals.
After taking into account other factors,
the investigators found a significant and independent association between an
undetectable viral load for 24 or more months and clearance of the infection
(OR = 1.018; 95% CI, 1.001-10.35; p < 0.039).
Finally, the researchers examined the
factors associated with high-risk cervical HPV infection at any time during the
Their first analysis showed that older age
(p < 0.001), a longer period of time with a CD4 cell count above 500
cells/mm3 (p < 0.0001) and longer duration of viral suppression
(p < 0.0001) were all associated with lower risk of carrying high-risk
After taking into account possible
confounders, they established that age under 30 years was a risk factor for
infection at any point during the study (OR = 3.13; 95% CI, 1.8-5.6; p <
This risk was decreased significantly by
having a CD4 cell count above 500 cells/mm3 for at least 18 months
(OR = 0.88; 95% CI, 0.82-0.94; p = 0.0002) and by having a viral load below 50
copies/ml for 40 or more months (OR = 0.81; 95% CI; 95%, 0.76-0.86; p <
The authors believe there are biological explanations
for their findings, given that “uncontrolled HIV viral load is responsible not
only for CD4 cells destruction but also for decreasing other immune functions
not measurable in routine practice and that are correlated with HRHPV infection
control such as cytokines production”.
The authors call for further research to
see if early HIV therapy reduces the risk of high-risk HPV infection and