Adults 45 to 70, female only, with HIV Infection or Vaginal Atrophy. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Change in Most Bothersome Symptom (MBS) of Vaginal AtrophyPrimary· Between baseline (Visit 2) and 12 weeks (Visit 5)
Change in the severity of MBS of vaginal atrophy as reported during the baseline visit was assessed at 12 weeks (Visit 5). During the baseline visit, participants were asked to identify their MBS and assess the severity of the MBS on an ordinal scale of "None," "Mild," "Moderate," or "Severe." During the follow-up visit at 12 weeks participants were again asked to identify and assess the severity of their MBS. The degree of severity of the MBS reported at baseline was then compared to the severity of the MBS reported at 12 weeks and categorically summarized and reported as either "Severity Inc
Itching
Group
Value
95% CI
Estradiol Vaginal Insert
0
No Treatment
1
Estradiol Vaginal Insert
8
No Treatment
4
Estradiol Vaginal Insert
0
No Treatment
1
Dryness
Group
Value
95% CI
Estradiol Vaginal Insert
0
No Treatment
1
Estradiol Vaginal Insert
9
No Treatment
3
Estradiol Vaginal Insert
1
No Treatment
6
Soreness
Group
Value
95% CI
Estradiol Vaginal Insert
0
No Treatment
0
Estradiol Vaginal Insert
1
No Treatment
0
Estradiol Vaginal Insert
0
No Treatment
0
Irritation
Group
Value
95% CI
Estradiol Vaginal Insert
0
No Treatment
0
Estradiol Vaginal Insert
0
No Treatment
0
Estradiol Vaginal Insert
0
No Treatment
0
Dyspareunia
Group
Value
95% CI
Estradiol Vaginal Insert
0
No Treatment
0
Estradiol Vaginal Insert
2
No Treatment
0
Estradiol Vaginal Insert
0
No Treatment
0
Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus)Primary· Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
The relative abundance of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing will be calculated by dividing the total number of L crispatus sequences detected in a sample by the total number of sequences from all bacterial species detected in the same sample. This proportion will be expressed as a percentage. The change in relative abundance between baseline (visit 2) and 12 weeks (visit 5) will be summarized by study arm.
Group
Value
95% CI
Estradiol Vaginal Insert
-1.37
± 4.25
No Treatment
-6.9
± 25.14
Vaginal Microbiome - Relative Abundance of Bacterial Vaginosis Associated SpeciesSecondary· Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
The relative abundance of bacterial vaginosis (BV) associated bacterial species as quantified by lllumina MiSeq sequencing, will be calculated by dividing the total number of the individual BV-associated species sequences in a sample by the total number of sequences from all bacterial species detected in the same sample. This proportion will be expressed as a percentage. The change in relative abundance between baseline (visit 2) and 12 weeks (visit 5) will be summarized by study arm for the 3 most common BV-associated species; Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vagi
G. vaginalis
Group
Value
95% CI
Estradiol Vaginal Insert
3.15
± 27.69
No Treatment
-1.22
± 17.03
F. vaginae
Group
Value
95% CI
Estradiol Vaginal Insert
-5.17
± 7.49
No Treatment
-1.14
± 8.72
P. bivia
Group
Value
95% CI
Estradiol Vaginal Insert
-0.82
± 1.79
No Treatment
-1.09
± 2.75
Change in Vaginal Cytokine and Chemokine ConcentrationsSecondary· Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Change in concentrations from baseline of vaginal cytokines and chemokines in cervicovaginal lavage (CVL) was determined. Following assay, concentrations for the following cytokines and chemokines, as individually expressed, were reported in picograms per milliliter (pg/mL): IL-1A, Interleukin-8 (IL8); Interferon-gamma inducible protein 10 (IP-10); Monocyte Chemoattractant Protein-1 (MCP-1); and Secretory Leukocyte Protease Inhibitor (SLPI). Change in concentrations for the respective cytokines and chemokines from baseline are summarized by study arm using basic descriptive statistics.
IL-1A
Group
Value
95% CI
Estradiol Vaginal Insert
0.17
± 0.53
No Treatment
-0.07
± 0.14
IL-8
Group
Value
95% CI
Estradiol Vaginal Insert
-0.07
± 0.28
No Treatment
0.11
± 0.07
IP-10
Group
Value
95% CI
Estradiol Vaginal Insert
-0.04
± 0.23
No Treatment
0.02
± 0.06
MCP-1
Group
Value
95% CI
Estradiol Vaginal Insert
-0.13
± 0.02
No Treatment
0.04
± 0.21
SLPI
Group
Value
95% CI
Estradiol Vaginal Insert
0.18
± 0.03
No Treatment
-0.07
± 0.00
Change in Vaginal Symptom Index (VSI)Secondary· Between Baseline (Visit 2) and 12 weeks (Visit 5)
Change in VSI was determined between Visit 2 and Visit 5. The VSI is a composite measure, calculated as the mean of 5 vaginal symptoms: dryness, itching, irritation, soreness, dyspareunia. Each symptom was given a score of 0-3 corresponding to either no symptoms, mild, moderate, or severe symptoms.
The number/percentage of participants with detectable concentrations of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing, is summarized by study arm.
The number/percentage of participants with detectable concentrations of the three most common Bacterial Vaginosis-associated species: Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vaginae); and Prevotella bivia (P. bivia), as quantified by lllumina MiSeq sequencing, is summarized by study arm.
G. vaginalis
Group
Value
95% CI
Estradiol Vaginal Insert
11
No Treatment
16
F. vaginae
Group
Value
95% CI
Estradiol Vaginal Insert
11
No Treatment
11
P. bivia
Group
Value
95% CI
Estradiol Vaginal Insert
8
No Treatment
9
Change in Vaginal Microbiome - Detectable Lactobacillus Crispatus (L. Crispatus)Secondary· Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Change from baseline in the percentage of participants with detectable concentrations of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing, is summarized by study arm. The value was obtained by calculating the percentage difference in participants with a detectable level at baseline (Visit 2) when compared to 12 weeks (Visit 5).
Group
Value
95% CI
Estradiol Vaginal Insert
-9.1
No Treatment
-8.0
Change in Vaginal Microbiome - Detectable Bacterial Vaginosis-Associated SpeciesSecondary· Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Change from baseline in the percentage of participants with detectable concentrations of the three most common Bacterial Vaginosis-associated species: Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vaginae); and Prevotella bivia (P. bivia), as quantified by lllumina MiSeq sequencing, is summarized by study arm. Values were obtained for each species by calculating the percentage difference in participants with a detectable level at baseline (Visit 2) when compared to 12 weeks (Visit 5).
G. vaginalis
Group
Value
95% CI
Estradiol Vaginal Insert
-13.6
No Treatment
8.0
F. vaginae
Group
Value
95% CI
Estradiol Vaginal Insert
0
No Treatment
-4.0
P. bivia
Group
Value
95% CI
Estradiol Vaginal Insert
-13.6
No Treatment
-24.0
Adverse events — posted to ClinicalTrials.gov
Time frame: Up to 13 weeks following randomization.
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Estradiol Vaginal Insert
Serious: 4/33 (12%)
Deaths: 1/33
No Treatment
Serious: 2/27 (7%)
Deaths: 0/27
Serious adverse events (6 terms)
Reaction
System
Estradiol Vaginal Insert
No Treatment
Hypoglycemia
Metabolism and nutrition disorders
—
—
Myocardial Infarction
Cardiac disorders
—
—
Hospitalization for Gastrointestinal Bleed (GIB)
Gastrointestinal disorders
—
—
Fractured Right Distal Fibula
Injury, poisoning and procedural complications
—
—
Liver Cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
During menopause, there is a decrease in a hormone estrogen, which leads to aging of the vagina. Vaginal aging includes changes in the type and amount of healthy bacteria in the vagina, inflammation and a breakdown of natural barriers that keep the vagina healthy and protected from infections. Some menopausal women develop a condition called vaginal atrophy, which causes vaginal dryness, irritation, pain with sex, and itching. We are testing whether an estradiol tablet placed inside the vagina will lead to fewer changes in the types of bacteria present in the vagina, improve vaginal atrophy symptoms and ultimately keep the vagina healthier for a longer. This is important for women with HIV as they are living longer, healthier, sexually active lives due to successful treatment with antiretrovirals.
Publications & conference data
3 peer-reviewed publications reference this trial (live from Europe PMC):
NCT06900829 — #AWARE.HIV Europe: Supporting Healthcare Professionals to Find Undiagnosed HIV in European Hospitals: An Effectiveness-i
· NA
· recruiting
NCT06908252 — MAPS PrEP Van Study
· Phase 4
· recruiting
NCT07042945 — MK-4646 Multiple Dose Trial in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-4646-003)
· Phase 1
· recruiting
NCT06716450 — Multiplo Tp/HIV Self-Test
· NA
· recruiting
NCT07086989 — Cardiovascular Risk in Children With Chronic Conditions Study
· recruiting
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Kerry Murphy
Last refreshed: 14 March 2025
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04079218.