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Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia
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AIDS May 8 2018 - Carlander, Christinaa,b; Wagner, Philippeb; Beirs, Astrid, vanc; Yilmaz, Aylind; Elfgren, Kristinae; Dillner, Joakimf; Sonnerborg, Andersa; Sparen, Parg
In our comprehensive, population-based cohort study with essentially complete follow-up, women living with HIV had more treatment failure and recurrence, after treatment of CIN2+, than HIV-negative women. Suppressive ART and CD4 counts above 499 at time of treatment of CIN2+ were associated with effective treatment of CIN2+. Additionally, CD4 count at time of treatment of CIN2+ seems to be a better predictor of treatment success than nadir CD4 count.
To our knowledge, this is the first study showing an association between suppressive ART and successful treatment of CIN2+ in WLWH. In countries where the burden of HIV is high and access to regular cervical cancer screening, HPV vaccination and treatment of CIN2+ is poor it is especially important with early HIV diagnosis, access to ART, and continuum of care to reach successful CIN2+ treatment.
Suppressive ART was associated with effective treatment of CIN2+. A majority of studies using only self-reported use of ART as a measure of effective ART have not found an association between ART and successful treatment [9, 10, 12]. In an early smaller study, Robinson et al. found less recurrence (in our study defined as treatment failure) in WLWH on self-reported ART compared to those without, although there was no measure of effect analysis in that study [15]. Reimers et al. did not find an association between HIV-RNA levels and treatment failure [13]. Contrary to our study, both these studies included women treated for CIN1 despite the fact that this is usually a self-healing lesion.
Among all participants, 30 (21%) WLWH and 20 (7%) HNW had treatment failure (Table 1). WLWH were more than three times more likely to have a treatment failure (OR 3.7 [95% CI 2.0- 6.8], Table 2) than HNW. When restricting WLWH to those with suppressive ART at time of treatment of CIN2+ (n=75), the association decreased and was no longer statistically significant (OR 1.8, [95% CI 0.8-4.2]). Grade of lesion was significantly associated with treatment failure in
WLWH only (Table 2). Treatment modality and nativity was not significantly associated with treatment failure in logistic regression analysis (Table 2). We were not able to adjust for smoking due to lack of adequate registration in medical records of this variable. Positive surgical endo/exo-cervical margins at time of treatment were also inadequately registered in medical records.
There were only 9 cases of treatment failure among women with suppressive ART at time of treatment of CIN2+. Advanced immunosuppression (CD4 count <200 cells/μL) at time of treatment of CIN2+ was associated with more than eight times higher odds ratio of treatment failure than a CD4 count ≥500 cells/μL (OR 8.5 [95% CI 2.3-30.7], Table 2). Although treatment failure was associated with low median nadir CD4 count in univariate analysis (Table 3), CD4 nadir <200 was not significantly associated with higher odds ratio of treatment failure compared with nadir CD4 count ≥350 cells/μL (OR 6.5 [95% CI 0.8-53.6]) in multivariate analysis and the association decreased even more when adjusting for CD4 count at time of treatment in the same model (Table 2). Earlier decade of HIV-transmission was associated with treatment failure in univariate (Table 3) but not in multivariate analysis (Table 2). Mode of HIV transmission wasnot significantly associated with treatment failure (Table 2).
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