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Low CD4 Count, Suboptimal HIV Treatment Linked to Higher Anal Cancer Risk

People with HIV who experienced extensive immune deficiency or who used early antiretroviral drugs before the advent of combination highly-active antiretroviral therapy (HAART) in the mid-90s may be at greater risk for developing anal cancer, according to a retrospective analysis published in the January 28 edition of AIDS.

People living with HIV have a high prevalence of human papillomavirus (HPV) infection, which can cause abnormal cell changes (dysplasia or neoplasia) that can progress to anal, cervical, and other genital cancers.

Antiretroviral therapy (ART) does not prevent anal intraepithelial neoplasia. In fact, several observational studies have seen rising rates of anal neoplasia and cancer among men who have sex with men (MSM) since the arrival of effective combination ART, as HIV positive people live longer. It remains unclear whether extent of immune deficiency predicts anal neoplasia or cancer, as study findings are inconsistent.

Katrina Duncan and colleagues aimed to learn more about the impact of antiretroviral therapy on the time it takes to develop anal cancer. They performed a retrospective analysis of cases of anal cancer in a cohort of HIV positive gay and bisexual men receiving antiretrovirals between 1988 and 2008, comparing cases occurring in the pre-HAART era (before 1996) and HAART era (1996-2008). The researchers looked at 37 cases of anal cancer in a cohort of 1654 HIV positive men who have sex with men.

Results

• 70% of the men who developed anal cancer used early antiretrovirals prior to HAART, while 30% started HIV treatment in the HAART era.
• The median CD4 T-cell count among men with anal cancer was low, at 70 cells/mm³, with a range of 0 to 130 (200 is the cutoff for a diagnosis of AIDS).
• Men who started treatment pre-HAART had a significantly shorter average time to development of anal cancer than those who started in the HAART era (adjusted hazard ratio [HR] 3.04).
• Men treated pre-HAART were significantly more likely to have a nadir (lowest-ever) CD4 count below 100 cells/mm³ (adjusted HR 2.21), as well as a longer duration of time spent with a CD4 count that low (adjusted HR 1.33).

"Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer," the study authors summarized. "HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART."

"Our results suggest that early use of HAART may delay progression to anal cancer," they concluded.

1/21/15

Reference

KC Duncan, KJ Chan, CG Chiu, et al. HAART slows progression to anal cancer in HIV-infected MSM. AIDS 29(3):305-311. January 28, 2015.