| |
HAART slows progression to anal cancer in HIV-infected MSM
|
| |
| |
Download the PDF here
"This is the first Canadian study to evaluate a cohort of HIV-positive MSM enrolled in a population-based free ART programme to assess the impact of antiretrovirals on the development of anal cancer. Similar to other cohort studies, we found immunosuppression (CD4+ cell count nadir <100 cells/ml, duration of CD4+ cell count <100 cells/ml) to be an important risk factor for development of anal cancer [2-5]. However, unlike other studies, we found that individuals treated during the HAART era (1996-2008) had a longer time to the development of invasive anal cancer than those treated in the pre-HAARTera (before 1996)."
"Our study shows that starting antiretrovirals in the pre-HAART era was associated with an increased risk of anal cancer versus high-grade AIN. This raises the question of whether antiretrovirals in the HAART era are somehow protective in preventing progression of dysplasia to cancer."
"Overall, the current study raises the interesting possibility that HAART may prolong time to development of invasive anal cancer in HIV-positive MSM. If externally validated, this would support more widespread testing policies to identify HIV-positive individuals earlier in the course of infection, so that they can be offered early initiation of antiretrovirals, thereby preventing immunosuppression, and potentially decreasing the burden of anal cancer."
"The incidence rate of anal cancer in the pre-HAARTera was much higher in our study (370 per 100 000 person years) than in other studies (10-20 per 100 000 person years) [1-4,11,12]. The reason for this discrepancy may be due to a difference in cohorts, and our inability to determine whether some men in our registry were MSM.
The proportion of anal cancer in our cohort (2.2%) is much larger than any other cohort (<1%). However, the rate of anal cancer in the general population in British Columbia is similar to rates reported elsewhere (men 1.1/100 000 person-years) [13]. Our cohort consists of only HIV-positive MSM receiving antiretrovirals, whereas other cohorts have included non-MSM, and likely had fewer individuals receiving antiretrovirals during the pre-HAARTera. Having a cohort with HIV-positive MSM who are at a higher risk for anal cancer than other HIV-positive populations, and receiving antiretrovirals, which may prolong survival, and therefore the exposure period of developing anal cancer, may explain the difference in anal cancer rates when comparing our cohort with others."
HAART slows progression to anal cancer in HIV-infected MSM.
AIDS Dec 3 2014
Duncan, Katrina C.; Chan, Keith J.; Chiu, Connie G.; Montaner, Julio S.G.; Coldman, Andy J.; Cescon, Angela; Au-Yeung, Christopher G.; Wiseman, Sam M.; Hogg, Robert S.; Press, Natasha M.
Abstract
Objective: Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM.
Design: A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008.
Methods: Time from first CD4+ cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008).
Results: Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4+ cell count nadir was 70 cells/[mu]l (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [AHR 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4+ cell count nadir less than 100 cells/[mu]l (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4+ cell count less than 100 cells/[mu]l (AHR 1.33, 95% CI 1.11-1.58, P = 0.002).
Conclusion: Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. 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.
EXCERPTS
Cohort studies have shown that rates of anal cancer have increased in HIV-positive MSM over the past 10-20 years. However, the impact of ARTs on the development of anal cancer is less clear than their role in precursor lesions [2,5,9]. The purpose of this study is to investigate the role of ARTs in the development of invasive anal cancer in a cohort of HIV-positive MSM receiving ARTs. A second purpose was to determine risk factors for high-grade AIN lesions compared with invasive anal cancer in this group.
Of the 37 cancer cases, 26 initiated antiretrovirals in the pre-HAART era (prior to 1996) compared with 11 cases that started therapy during the HAART era (1996-2008). Incidence rates per 100 000 person-years were 370 in the pre-HAARTera versus 93 in the HAARTera (P<0.001). The overall incidence ratewas 196 per 100 000 person-years.
The Kaplan-Meier plot shows that time from first CD4 cell count/viral load to anal cancer diagnosis was shorter in the pre-HAARTera (log rank P<0.001) (Fig. 1). Cox regression analysis for time to anal cancer also identified CD4 cell count nadir less than 100 cells/ml [AHR 2.21 (1.06-4.62), P=0.035] and duration of time with CD4
cell count less than 100 cells/ml [AHR 1.33 (1.11-1.58), P=0.002] as risk factors for shorter duration to development of anal cancer (Table 2). However, less severe immunosuppression, including CD4 cell count nadir between 100 and 200 cells/ml, and duration of time with a CD4 cell count between 100 and 200 cells/ml, did not
achieve significance. Adherence to antiretrovirals, or resistance to antiretroviral classes, also did not reach significance. HIV viral load testing was not available earlier in the study period, and, therefore,was not used as a variable.
To determine which HIV-positive MSM receiving antiretrovirals would be at the highest risk for development of anal cancer, we compared the 33 anal cancer cases with HIV-positive MSM on antiretrovirals with biopsy-proven high-gradeAIN (n1/4144) identified through our screening programme at the Anal Dysplasia Clinic (four anal cancer cases were excluded because they overlapped with the high-grade AIN group) (Table 3). Logistic regression identified CD4 cell count nadir less than 100 cells/ml [AOR 3.08 (1.30-7.32), P1/40.011] as a risk factor for the development of anal cancer.Receiving antiretrovirals in the pre-HAART era was also a risk factor for the development of anal cancer [AOR 2.67 (1.09-6.55)] (Table 4). High-grade AIN cases were not significantly different from anal cancer cases with respect to time from first CD4 cell count/viral load to cancer or censor (13 versus 10 years), or duration of immunosuppression with CD4? cell count less than 200 cells/ml or less than 100 cells/ml.
|
|
| |
| |
|
|
|
