Starting antiretroviral treatment does not reduce the incidence or prevalence of cervical infection with human papillomavirus

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Starting antiretroviral treatment does not reduce the incidence or prevalence of cervical infection with human papillomavirus, US investigators report in the online journal BMC Infectious Diseases. All types of the virus persisted, including those associated with a high risk of cervical cancer.

Nor did the investigators find any evidence that better increases in CD4 cell count after starting HIV treatment increased the chances of clearing cervical infection with human papillomavirus (HPV).

Moreover, many patients who were taking HIV therapy acquired infection with high-risk strains of human papillomavirus.

Glossary

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.

cervix

The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

strain

A variant characterised by a specific genotype.

 

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.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

“There is no immediate effect of HAART [highly active antiretroviral therapy] on HIV-infected adolescents, especially with regard to high-risk and vaccine-type HPV infection prevalence, persistence, or clearances,” comment the study’s authors. “Additionally, there is no clear pattern of HPV infection or clearance with respect to immune reconstitution (based on CD4 T-cell counts) from HAART.”

Antiretroviral therapy has been associated with remarkable improvements in the prognosis of many HIV-positive patients. Rates of AIDS-defining illnesses have fallen dramatically, including those of the HIV-related cancers Kaposi’s sarcoma and non-Hodgkin lymphoma.

Cervical cancer is also classified as an AIDS-defining cancer, and research suggests that diagnoses of this malignancy have increased since antiretroviral therapy was introduced.

Like anal cancer (rates of which have also increased), cervical cancer is associated with long-term infection with certain strains of human papillomavirus. This can cause cell changes that lead to cancer.

Information about the impact of HIV therapy on the clearance of cervical human papillomavirus is inconsistent. Some studies suggest that the immune restoration that results from antiretroviral therapy helps clear the infection, but other research has found no evidence of this.

Investigators from the US REACH (Reaching for Excellence in Adolescent Care and Health) cohort study wished to clarify this important question.

They therefore monitored the prevalence, persistence and incidence of cervical human papillomavirus infection in 373 adolescents with HIV (227) or at risk of HIV. All were aged between 12 and 19, and the HIV-infected patients acquired the infection through sex or drug use. 

These individuals were monitored for cervical human papillomavirus infection every six months, and the HIV-positive patients had their CD4 cell counts monitored at regular intervals.

The HIV-positive adolescents had a variety of antiretroviral treatment histories. A total of 100 had follow-up data before and after the initiation of HIV treatment; 57 started HIV therapy immediately they entered the cohort; and 70 never took anti-HIV drugs.

Overall, 70% of study participants had cervical human papillomavirus infection at baseline, and 70% of those who were uninfected at baseline acquired the infection during follow-up.

On average the patients were followed for a little over two years.

Individuals starting HIV treatment showed good increases in their CD4 cell counts from a baseline of 471 cells/mm3 to 525 cells/mm3.

Before they started antiretroviral therapy, the HIV-positive participants had a prevalence of between 1 – 17% of infection with a high-risk type of human papillomavirus.

Prevalence in the HIV-negative individuals was between 1% -10%.

Starting treatment with anti-HIV drugs had no impact on the prevalence of high-risk infections (1 – 18%).

There was a high incidence of infections in both the HIV-positive and HIV-negative patients, with a trend for higher incidence among those with HIV.

Although CD4 cell counts increased in patients starting HIV therapy, this did not affect human papillomavirus infections and clearance patterns.

 “Overall, the results suggest that HAART has no effect on high- or possible-carcinogenic HPV infections”, comment the investigators.

For example, incidence of HPV 16 was 6.54 per 100 person years before HIV treatment was started and 6.67 per 100 person years after.

Similarly, the incidence of HPV 18 was 4.66 per 100 person years in the period before antiretroviral therapy was started and increased to 6.26 per 100 person years after patients started taking anti-HIV drugs.

Incidence of some other high-risk strains of the virus was even higher. That of HPV 53/66 was 9.83 per 100 person years in the period before HIV therapy, but was 12.80 after treatment was started.

“We observed higher prevalence and incident of possible carcinogenic…HPV types in the after HAART initiation period. Thus prevention of HPV acquisition is important, especially in vulnerable populations such as sexually active adolescents.”

The investigators acknowledge that the study’s small sample size is a potential limitation. Nevertheless they conclude that starting HIV treatment “did not show immediate effect on high-risk and vaccine type HPV incidence, clearance, and persistence.”

References