Anal HSIL is common in HIV-infected women. Substantial numbers of HSIL would have been missed by strictly adhering to existing AC screening guidelines. These results support routine screening of all HIV-infected women regardless of human papillomavirus history or sexual practices.
Background
Despite pre-exposure prophylaxis (PrEP) being highly effective at preventing HIV, HIV infections among individuals prescribed PrEP continue to occur. The vast majority of these new infections occur among individuals with sub-optimal adherence. One factor that is likely to decrease HIV incidence among PrEP users is a real-time, objective measurement of adherence. Monitoring adherence to PrEP can identify those at risk of becoming lost to follow-up and therefore at greater risk of HIV infection, those in need of additional layers of support to overcome barriers to PrEP, and individuals who need enhanced adherence support.
Objective
This paper reviews subjective and objective methods for monitoring PrEP including self-report, drug level monitoring (including serum, plasma, peripheral blood mononuclear cells [PBMC], red blood cell dried blood spots [DBS], hair, and urine) and by measuring participant interaction with the study drug (pill counts, medication event monitoring systems [MEMS] caps).
Clinical Use
A multitude of methods exist for monitoring and supporting adherence. Objective monitoring using DBS and urine will provide a more accurate picture of adherence compared to subjective and non-biomarker objective methods. Preliminary data show that detection of non-adherence using biomarkers, followed by augmented adherence support and counseling, is associated with improved adherence, although more research is needed. PrEP providers will need knowledge of and access to these various strategies, which will require investment and resource allocation from clinics and other PrEP care sites to provide these tools.
BACKGROUND:
The progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines.
OBJECTIVE:
This study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons.
DESIGN:
Using the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer.
SETTINGS:
This is a population-based study.
PATIENTS:
Included were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III.
MAIN OUTCOME MEASURES:
The primary outcome measured was incident squamous cell carcinoma of the anus.
RESULTS:
Study subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%–2.5%) and 5.7% (95% CI, 4.0%–8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04).
LIMITATIONS:
The identification of some incident cancer episodes used surrogate measures.
CONCLUSIONS:
In our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.
Human immunodeficiency virus is associated with alterations of the immune microenvironment of anal HSILs manifested by increased local lymphocytic infiltrates, predominately CD8+. Human immunodeficiency virus seropositivity and excess mucosa-infiltrating CD8+ cells may be associated with ablation resistance.
Lone radiation may be associated with adequate oncologic outcomes when used to treat older and sicker patients with stage I anal cancer. Physicians should discuss the potential benefits and harms of adding chemotherapy for the treatment of these patients. See Video Abstract at http://links.lww.com/DCR/A628.
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