Long-term suppression of viral load and sustained CD4 cell increase reduce risk of cervical HPV infection for HIV-positive women

Michael Carter
Published: 01 April 2013

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 HPV infections.

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 load.

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 study.

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 strains.

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 < 0.001).

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 < 0.001).

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 cervical cancer.

Reference

Konopnicki D et al. Sustained viral suppression and higher CD4 cell count reduces the risk of cervical persistent infection with high risk human papillomavirus in HIV-positive women. J Infect Dis, online edition, 2013.