Akseptabilitet og gjennomførbarhet av kombinasjonsbehandling for cervical precancer blant sørafrikanske kvinner som lever med HIV (ACT 2)

Eksperimentell: 5 Fluorouracil (5FU) Cream

Participants self-administered 2 grams intravaginal 5FU cream at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).

Legemiddel: 5 Fluorouracil (5 FU) krem

Intravaginal lokal kjemoterapi, 5-fluorouracilkrem

Andre navn:

• Carac
• Efudex
• Fluoroplex

Placebo komparator: Placebo Cream

Participants self-administered intravaginal placebo cream (an inert emollient that mimics the 5FU cream) at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).

Legemiddel: Placebo

Intravaginal topisk placebokrem

Number of Participants Retained in the Study Through Week 24

Retention was defined as the number of participants who remained in follow-up and completed the Week 24 study visit. The number and percentage of participants retained at Week 24 were reported for each study arm.

Number of Participants With ≥80% Acceptability Summary Score at Week 10

Acceptability was defined as a summary score ≥80% on a 7-item questionnaire administered at Week 10. Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28. A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score. The number and percentage of participants meeting this definition were reported for each study arm.

Number of Participants With ≥80% Acceptability Summary Score by Week 24

Acceptability was defined as a summary score ≥80% on the same 7-item questionnaire administered at Week 24. Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28. A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score. The number and percentage of participants meeting this definition were reported for each study arm.

Number of Participants Experiencing a Treatment-Related Grade ≥2 Adverse Event or Grade 1 Genital Lesion

A safety event was defined as any Grade 2 or higher adverse event (AE), or any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to the study drug. Adverse events were assessed from Week 4 (randomization) through Week 24. The number and percentage of participants experiencing at least one such event were reported for each study arm.

Number of Participants Unable or Unwilling to Apply ≥50% of Study Cream Doses Due to Dose-Limiting Toxicity

A tolerability event was defined as inability or unwillingness to apply ≥4 of 8 planned doses of the study treatment due to a dose-limiting toxicity (DLT). A DLT was defined as (1) any Grade 2 or higher AE, or (2) any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to study drug and resulted in an investigator decision to reduce the number of doses or discontinue study treatment. Tolerability was assessed from randomization through the dosing period (Week 18), with follow-up censored at the last tolerability assessment for participants who exited early without experiencing an event. The number and percentage of participants experiencing a tolerability event were reported for each study arm.

Number of Participants Adherent to ≥75% of Study Cream Doses Based on Ultraviolet Inspection

Adherence was defined as administration of at ≥6 of 8 planned doses of study treatment, as determined by ultraviolet inspection of returned applicators. Applicator collection occurred through Week 24, including for participants who completed dosing earlier, to allow complete ascertainment of dose use. Each applicator was independently assessed by ≥2 reviewers; in cases of disagreement, a third reviewer adjudicated the result. Participants were classified as adherent if ≥6 applicators showed evidence of use. Participants who did not meet this threshold, including those with missing or incomplete applicator data, were classified as non-adherent. The number and percentage of participants meeting this definition were reported for each study arm.

Percent of Participants With CIN2/3 at Baseline Who Regressed to CIN1 or Normal Histology at Week 24

The analysis population included all randomized participants, all of whom had CIN2 or CIN3 at baseline (Week 0) confirmed by loop electrosurgical excision procedure (LEEP) histology. The analysis population was restricted to participants who completed the Week 24 visit and had cervical biopsy results available. This included 89 participants in the placebo arm and 81 participants in the 5FU arm. Regression was defined as improvement from CIN2 or CIN3 at baseline to CIN1 or normal histology at Week 24, as assessed by cervical biopsy. Participants missing Week 24 data were not included and not considered to have experienced CIN2/3 regression. The number and percentage of participants meeting this definition were reported for each study arm. The Wilson score method was used to estimate 95% confidence intervals around percentages.

Percent of Participants With Baseline High-Risk HPV Who Achieved Genotype-Specific Clearance at Week 24

The analysis population was restricted to participants with at least one high-risk HPV (hrHPV) genotype detected at baseline and with hrHPV results available at Week 24. A total of 69 participants in the 5FU arm and 80 participants in the placebo arm met these criteria. High-risk HPV clearance was defined as absence at Week 24 of all hrHPV genotypes detected at baseline. Participants without baseline hrHPV infection or without Week 24 hrHPV results were excluded from this analysis. The number and percentage of participants meeting this definition were reported for each study arm. The Wilson score method was used to estimate 95% confidence intervals around percentages.