Cervical Neoplasia and Highly Active Antiretroviral Therapy

Extract

Previous studies have clearly demonstrated that human immunodeficiency virus (HIV)-infected women, especially those with low CD4+ T-cell counts, are at increased risk for infection with human papillomaviruses (HPVs) ( 1 , 2 ), the etiologic agent for the development of cervical cancer. Furthermore, HIV infection has been shown to increase a woman's risk of cervical cancer and of cervical cancer precursor lesions ( 3 ), including high-, and especially, low-grade squamous intraepithelial lesions (SIL) ( 4 – 7 ). The mechanism by which HIV increases the risk of HPV infection and cervical neoplasia is believed to be related, in part, to HIV-induced immunodeficiency and the resulting inability to control HPV infection ( 8 ). Given this potential mechanism, it has been proposed that highly active antiretroviral therapy (HAART), which is known to lead to clinically significant immunologic reconstitution ( 9 , 10 ), might alter the course of HPV-related cervical lesions in HIV-infected women. At least seven studies ( 11 – 17 ) have examined the effects of HAART on the course of cervical lesions, but it is still unclear whether HAART substantially affects the natural history of SIL. Although some studies ( 11 – 14 ), including one by the Women's Interagency HIV Study (WIHS) Group ( 14 ), reported an association of HAART with regression of cervical lesions, others did not ( 15 – 17 ). Indeed, recent data from the HIV Epidemiology Research Study, a multicenter American study of HIV infection, failed to show any beneficial effect of HAART on regression of cervical lesions in 774 HIV-positive women followed at 6-month intervals for an average of 5.5 years ( 17 ). The inconsistent findings among studies likely reflect small numbers of study participants, different study outcome definitions, a focus on prevalent cervical lesions, and differences in the timing and duration of the therapy in each study.