The use of highly active antiretroviral therapy (HAART) has greatly improved survival rates among people with HIV/AIDS (PHAs). This occurs because HAART suppresses production of HIV, which allows the immune system to begin repairing itself. Unfortunately, the immune system does not become fully restored, perhaps because a low level of viral activity occurs even though HAART is used. As a result, the immune system is not 100% effective and some complications can still occur. This means that although the level of restored immunity may be enough to help PHAs resist many AIDS-related infections, it does not appear to be sufficient to prevent the development of some cancers.
A virus called HPV (human papilloma virus) causes cervical and anal lesions and, in some cases, those lesions can turn into tumours. Because of their weakened immune systems, PHAs co-infected with HIV and HPV are at increased risk for HPV-related cancers. In the time before HAART, one study found that HIV positive women were five times more likely than HIV negative women to develop abnormal growths on the cervix.
To understand the impact of HAART on HPV infection and cervical growth, researchers in Milan, Italy, recruited 163 HIV positive women between 1995 and 1997 and monitored their health. The average age of the women was 34 years. Researchers divided the women into three groups based on their use of anti-HIV therapy. Their profile at the start of the study was as follows:
Group 1 – no therapy
Group 2 – one or two nucleoside analogues (nukes)
Group 3 – HAART
All subjects received regular Pap smears along with gynecologic exams. Abnormal growths were removed for analysis. Those women who had pre-cancerous cervical lesions had them zapped with a mild electric current. On average, researchers monitored subjects for about 1½ years.
There are many strains of HPV, only some of which — such as HPV-16, HPV-18, HPV-31 and HPV-33 — are considered to place women at high risk for developing pre-cancerous cervical growths. Researchers found that only 65% of the women had detectable HPV. In these women, the following proportion had the following types of HPV:
At the start of the study, results of Pap smears were as follows:
In general, women with low CD4+ cell counts were more likely to have cervical growths than women with higher cell counts. The proportion of women who had pre-cancerous growths in different CD4+ cell count ranges were as follows:
Not surprisingly, the researchers observed that only those women who used HAART had significantly increased CD4+ cell counts during the study.
A total of 53 women had colposcopies during which abnormal cervical growths were removed for analysis. Pre-cancerous cells were detected in only seven of these 53 women.
According to the data analysis, the researchers found the following:
Despite the findings above, pre-cancerous cervical growths were not more likely to shrink in women receiving HAART or nukes alone compared to women receiving no anti-HIV treatment.
During the study, no cases of invasive cervical cancer were detected. The researchers did point out that two women using HAART who were not in the study but who sought medical care from their clinic while the study was ongoing, did develop this form of cancer. This anecdote underscores the fact that cervical cancer can occur in women using HAART.
The results of this study suggest that despite the use of HAART, HPV cervical infection and related disease continue in women who receive HAART. The study doctors emphasize the need for HIV positive women to receive regular gynecologic monitoring as part of their overall care.
REFERENCES
1. Wallin K-L, Wiklund F, Ångström T, et al. Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. New England Journal of Medicine 1999;341(22):1633-1638.
2. Lillo FB, Ferrari D, Veglia F, et al. Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: effect of highly active antiretroviral therapy. Journal of Infectious Diseases 2001;184:547-551.
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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