Chemtai Mungo

Feasibility of Intravaginal Artesunate as an Adjuvant HPV & Cervical Precancer Treatment Among Women Living With HIV in Kenya: Study Protocol for a Phase II Clinical Trial

Introduction Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), who account for 90% of deaths from the disease. Human papillomavirus (HPV) is responsible for 99% of cervical cancer cases. Women living with HIV (WLWH) have a higher risk of persistent HPV infection and a greater likelihood of developing cervical cancer. Prevention of cervical cancer requires effective screening and precancer treatment programs. In LMICs, the common treatment method for cervical precancer is thermal ablation. However, for WLWH, thermal ablation is associated with high rates of persistent HPV infection following treatment, a key risk factor for precancer recurrence. Adjuvant topical treatments with cytotoxic or antiviral properties may reduce HPV persistence following ablation. Preclinical and early-phase clinical trials indicate that topical artesunate is active against HPV-associated anogenital lesions, including cervical precancer, and can induce HPV clearance. Consequently, intravaginal artesunate may improve HPV clearance following thermal ablation, although no clinical trials have investigated this. Methods We are conducting a phase II, double-blind, randomized, placebo-controlled trial among 120 HIV seropositive women in Kenya to investigate the feasibility of self-administered intravaginal artesunate pessaries as adjuvant therapy following thermal ablation treatment for cervical precancer. The primary outcome is type-specific HPV clearance 6 months after randomization. Secondary outcomes are safety, adherence, acceptability, uptake, and retention. Participants will be enrolled at least 4 weeks after ablation and will self-administer pessaries on weeks 1, 3, and 5, with alternating drug-free weeks. Study follow-up will extend to 24 weeks after randomization. Conclusion High rates of persistent HPV infection in WLWH is a key limitation of thermal ablation, the most accessible cervical precancer treatment in LMICs. This trial will investigate the feasibility of repurposing topical artesunate as an adjuvant therapy to improve HPV clearance following thermal ablation in WLWH. Trial Registration ClinicalTrials.gov identifier: NCT06519994

Safety and adherence to self‐administered intravaginal 5‐fluorouracil cream following cervical intraepithelial neoplasia ( CIN ) 2/3 treatment among HIV ‐positive women in Kenya: A phase 1 clinical trial

Abstract Objective To determine the safety, tolerance, and adherence to self‐administered intravaginal 5% fluorouracil (5FU) cream as adjuvant therapy following cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) treatment among women living with HIV (WLWH) in Kenya. Methods A phase I pilot trial was performed among 12 WLWH in Kenya, aged 18–49 years between March 2023 and February 2024 ( ClinicalTrial.gov NCT05362955 ). Participants self‐administered 2 g of 5FU intravaginally every other week for eight applications. Safety was assessed using a standardized grading scale, and adherence was evaluated using self‐report, inspection of used applicators, and weighing of the study drug. Results The mean age and CD4 count were 43.9 years and 781 cells/mm 3 , respectively. Seven (58%) had an eighth‐grade education or less. All 12 reported at least one grade I adverse event (AE), one (8%) reported a grade 2 AE, no grade 3 or 4 AEs were reported. Increased vaginal discharge ( n  = 9, 75%) and irritation ( n  = 5, 42%), with a mean duration of 3.2 and 2.8 days, respectively, were the most commonly reported AEs. Provider‐observed AEs included grade 1 cervical erythema and superficial abrasions. All participants tolerated all eight 5FU doses, and 96% adherence was demonstrated. Conclusion Self‐administered 5FU following CIN2/3 treatment among WLWH in Kisumu, Kenya, was safe, tolerable, and associated with high adherence. Randomized trials are needed to investigate whether adjuvant 5FU can improve treatment outcomes or serve as primary cervical precancer treatment in sub‐Saharan Africa. A self‐administered therapy may be transformative in increasing access to treatment and, hence, secondary prevention of cervical cancer.

Real-World Cervical Cancer Screening Uptake and Predictors of Visual Inspection With Acetic Acid Positivity Among Women Living With HIV in Care Programs in Western Kenya

PURPOSE To achieve the WHO cervical cancer elimination targets, countries globally must achieve 70% cervical cancer screening (CCS) coverage. We evaluated CCS uptake and predictors of screening positive at two public HIV care programs in western Kenya. METHODS From October 2007 to February 2019, data from the Family AIDS Care and Education Services (FACES) and Academic Model Providing Access to Healthcare (AMPATH) programs in western Kenya were analyzed. The study population included women age 18-65 years enrolled in HIV care. Screening uptake was calculated annually and overall, determining the proportion of eligible women screened. Multivariate logistic regression assessed predictors of positive screening outcomes. RESULTS There were 57,298 women living with HIV (WLWHIV) eligible for CCS across both programs during the study period. The mean age was 31.4 years (IQR, 25.9-37.8), and 39% were on antiretroviral therapy (ART) at the first CCS-eligible visit. Of all eligible women, 29.4% (95% CI, 29.1 to 29.8) underwent CCS during the study period, 27.0% (95% CI, 26.5 to 27.4) in the AMPATH program, and 35.6% (95% CI, 34.9 to 36.4) in the FACES program. Annual screening uptake varied greatly in both programs, with coverage as low as 1% of eligible WLWHIV during specific years. Age at first screening, CD4 count within 90 days of screening, current use of ART, and program (AMPATH v FACES) were each statistically significant predictors of positive screening. CONCLUSION CCS uptake at two large HIV care programs in Kenya fell short of the WHO's 70% screening target. Screening rates varied significantly on the basis of the availability of funding specific to CCS, reflecting the limitations of vertical funding programs.

Efficacy of thermal ablation for treatment of biopsy‐confirmed high‐grade cervical precancer among women living with HIV in Kenya

AbstractThe World Health Organization recommends thermal ablation (TA) as an alternative to cryotherapy within “screen‐and‐treat” cervical cancer programs in low‐ and middle‐income countries (LMICs), including among women living with HIV (WLWH). Data on TA efficacy among WLWH are limited, however. We conducted a clinical trial to evaluate efficacy of TA for treatment of biopsy‐confirmed cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3) among WLWH in Kenya. Nonpregnant HPV‐positive WLWH age 25 to 65 years underwent colposcopy‐directed biopsy, and same‐day treatment with TA, if eligible. Women with biopsy‐confirmed CIN2/3 at baseline had colposcopy‐directed biopsies at 12 months to determine cure. A total of 376 participants underwent TA during the study period. At baseline, 238 (63.3%) had normal histology, 39 (10.4%) had CIN1, 15 (4.0%) had CIN2, 55 (14.6%) had CIN3, 7 (1.9%) had microinvasive cancer and 22 (5.6%) had indeterminate results. Twelve‐month follow‐up pathology results are available for 59 of 70 (84.3%) participants with CIN2/3 at baseline. Of these, 39 (66.1%, 95% CI 0.54‐0.99) had successful treatment, defined as biopsy‐confirmed CIN1 or normal findings, while 20 (33.9%, 95% CI 0.22‐0.46) had treatment failure, defined as persistent biopsy‐confirmed CIN2 or worse. Treatment failure was 23.1% (95% CI 0.17‐0.46) and 39.9% (95% CI 0.23‐0.51) among women with CIN2 and CIN3 at baseline, respectively. HIV‐positive women with CIN2/3 have high rates of treatment failure at 1‐year following thermal ablation. This highlights a significant limitation in the current WHO cervical cancer secondary‐prevention strategy and calls for strategies to optimize cervical precancer treatment in this population.