Early treatment to prevent anal HSIL
In the 2022 Conference on Retroviruses and Opportunistic Infections (CROI), Dr. Joel Palefsky from the University of California, the United States, presented the results of the ANCHOR study on the management of high-grade squamous intraepithelial lesions (HSIL) and its implications on clinical practice.1
Anal cancer is a common cancer among human immunodeficiency virus (HIV) patients compared with the general population and has been on the rise despite a lower incidence in the general population.1 Anal and cervical cancers are similar in the way that they are preceded by (HSIL).1 Studies have shown that treatment of cervical HSIL was proven to reduce the incidence of cervical cancer.1 However, routine screening and treatment of anal HSIL are not recommended due to the lack of supporting studies on their ability to prevent anal cancer.1 The limitations in preventing anal cancer may be due to the large and multifocal lesions found in many at-risk patients, missed lesion detection, or inadequate treatment of lesions.1
The aim of the ANCHOR study was to determine whether treating anal HSIL is effective and safe in reducing the incidence of anal cancer in people living with HIV, as well as to develop and implement an instrument for measuring its impact on quality of life, and identify host and viral biomarkers of progression to cancer.1
This multicenter study enrolled HIV patients of 35 years or older with anal HSIL and randomized (1:1) them to active monitoring (AM) or treatment.1 Randomization was stratified according to the study site, nadir CD4 count, and lesion size at randomization.1 Treatment arms included hyfrecation, infrared coagulation (IRC), fluorouracil (5-FU), or imiquimod and AM.1 In the AM arm, patients’ anal cytology, swabs, high-resolution anoscopy (HRA), and blood were monitored after 6 months, with annual biopsies or biopsies at any visit when there was a concern for cancer.1
A total of 4,446 individuals with a median age of 51 years and an HIV diagnosis of 17 years that was mostly well controlled (80%) were followed for 25-27 months. Of this population, 80% were males, 16% were females, and 4% were transgenders.1
Most patients were treated with office-based electrocautery ablation (92.9%) and 1 therapeutic modality (86%).1 Of the 32 diagnosed cancers, 9 patients were in the treatment arm compared with 21 patients in the AM arm.1 After a median follow-up of 25.8 months, anal cancer was reduced by 57% when patients were treated rather than actively monitored only (95% CI: 6%-80%, p=0.029).1 As a result, the Data and Safety Monitoring Board (DSMB) recommended the cessation of the study due to proven efficacy, and suggested treating all individuals in the AM arm.1
In terms of safety, 54 and 48 deaths were seen in the treatment arm and the AM arm, respectively, but none were related to the study.1 Overall, 43 study-related adverse events were seen in the treatment arm compared with 4 events in the AM arm.1
In conclusion, the treatment of anal HSIL was found to be effective in reducing the incidence of anal cancer.1 Therefore, the standard of care should include this study data when screening for and treating anal HSIL.1 However, a high number of cancer cases were detected in the treatment arm due to treatment failure, indicating a potential for treatment improvement.1 Also, screening optimization and the extrapolation of these results to other high-risk groups are needed.1
- Palefsky J. Treatment of Anal High-grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2022; February 12, 2022.
5-year outcomes of B/F/TAF in treatment-naïve adults
Bictegravir (B; BIC), emtricitabine (F; FTC), and tenofovir alafenamide (TAF) or B/F/TAF is a single-tablet coformulation that is recommended for people living with human immunodeficiency virus (HIV).1 It can be taken once daily without food restrictions, and has a high barrier to resistance with a favorable drug-drug interaction profile.1
This presentation reported the 5-year treatment outcomes of B/F/TAF in treatment-naïve adults. There were 2 randomized, double-blind phase 3 studies of B/F/TAF in treatment-naïve adults, namely study 1489 [B/F/TAF vs. dolutegravir/abacavir/lamivudine (DTG/ABC/3TC)] and study 1490 (B/F/TAF vs. DTG+F/TAF).1 After 144 weeks of blinded treatments, subjects were offered a continuation of B/F/TAF for 96 weeks as part of an open-label extension study.1 Efficacy was assessed as proportion with HIV-1 (ribonucleic acid) RNA <50 copies/mL at each visit after B/F/TAF using missing=excluded (M=E) analysis, safety and laboratory results.1
