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Better CD4 Gains on Antiretrovirals Linked to Clearance of Cancer-Causing HPV
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9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow
Mark Mascolini
A significantly higher percentage of human papillomavirus (HPV)-infected women with higher CD4 counts during follow-up (usually on antiretroviral therapy) cleared their HPV infection, according to results of Belgian HPV screening study that involved a high proportion of women born in Africa [1]. As in earlier studies, younger age and a lower CD4 count correlated with higher HPV prevalence. HPV can cause cervical cancer, an AIDS-defining cancer. Women with HIV run a higher risk of cervical cancer despite the advent of potent antiretroviral [2].
Of 466 HIV-infected women screened for HPV since 2002 with the Hybrid Capture II amplification test, this analysis by investigators at Saint Pierre University in Brussels excluded 140 (30%) because they already had a record of high-grade cervical dysplasia or cervical cancer. Of the remaining 326 women, 267 (82%) were African, 303 (93%) acquired HIV during sex with men, 72 (22%) smoked, and only 10 (3%) already had an AIDS diagnosis.
A large majority of these 326 women, 280 (86%), were taking antiretrovirals when screened for HPV. And 93% of women were taking antiretrovirals when follow-up testing established HPV clearance or persistence. Prescribing clinicians did not know the women's HPV status when they started antiretroviral therapy. Median CD4 count when treatment began stood at 225, and viral load averaged 95,000 copies. More than 85% of women reached a viral load below 50 copies at least once during follow-up.
HPV screening detected the virus in 152 of 326 women (47%) at least once. Because 140 of the 466 women originally screened were eliminated from this analysis because they already had high-grade dysplasia or cancer, the investigators estimated the overall prevalence of HPV infection in this cohort as 63% (292 of 466 women). Among the 100 of 152 HPV-positive women who had a repeat test, 51 had persistent HPV infection and 49 cleared their HPV.
Comparing the 152 women with a positive HPV test with the 174 who had a negative test, the researchers found that the positive group was significantly younger (median 35 versus 39 years, P = 0.0002), had a lower median CD4 count (364 versus 468, P < 0.0001), had a shorter median duration of follow-up with HIV infection (median 45 versus 78 months, P = 0.0001), and had a shorter median duration of antiretroviral therapy (35 versus 64 months, P = 0.0004). They did not report how many women with and without HPV were sexually active.
Comparing the 51 women with persistent HPV and the 49 who cleared their HPV, the Saint Pierre team isolated only one factor that independently predicted persistent infection--a lower CD4 count at the first HPV screen (median 301 versus 411, P = 0.0252).
Next the researchers compared CD4 counts in women with persistent versus cleared HPV as percent of follow-up time spent in four CD4 brackets between the first HPV screen and the time of clearance or persistence: under 200 CD4s, 200 to 349, 350 to 499, and 500 or more CD4s:
Percentage of follow-up time, persistent versus cleared HPV (overall P < 0.0001):
· Under 200 CD4s: 5318 days (13%) versus 1486 days (4%)
· 200 to 349 CD4s: 10,118 days (24%) versus 8620 days (23%)
· 350 to 499 CD4s: 11,344 days (27%) versus 10,837 days (29%)
· 500 or more CD4s: 14,711 days (36%) versus 16,836 days (45%)
· Total days: 41,491 (100%) versus 37,779 days (100%)
The marked differences in the under-200 group and the over-500 group suggested to the Saint Pierre researchers that better immune reconstitution on antiretroviral therapy favors clearance of cancer-causing HPV in HIV-infected women.
This analysis is limited in that not all women were taking antiretrovirals, so the CD4 counts compared cannot be entirely attributed to antiretroviral therapy. The investigators did not report HPV genotype or classify identified viruses as high or low risk, though they confined the analysis to genotypes they classified as oncogenic (16, 18, 29, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 68). Nor did the Saint Pierre team distinguish between women who reported being sexually active and those who did not. In a US natural history study involving 1848 women with HIV and 514 women without HIV, a CD4 count below 200 or an HIV load above 100,000 strongly correlated with new diagnosis of HPV infection, but correlated less strongly with persistent HPV [3].
References
1. Konopnicki D, Manigart Y, Scheen R, et al. Impact of HIV treatment on clearance of human papillomavirus (HPV) infection in HIV-infected women. 9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow. Abstract P289.
2. Cervical cancer. aidsmap.com. December 21, 2005. Available at http://www.aidsmap.com/en/docs/B80BF36D-935D-490B-9A19-A4CDFA67B574.asp. Accessed November 15, 2008.
3. Strickler HD, Burk RD, Fazzari M, et al. Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst. 2005;97:577-586.
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