HIV
Conditions
Keywords
HIV-negative, Women, At-risk
Brief summary
This study seeks to understand the immune cells in the cervical fluid of in the blood and genital tract of HIV-negative healthy female volunteers and to see if these cells can be modified using a combined anti-viral and antiinflammatory drug called maraviroc, a medicine used in the treatment of HIV infection.
Detailed description
In this study, the investigator seeks to understand the immune cells in the cervical fluid of HIV-negative healthy female volunteers, and to see if these cells can be modified using a combined anti-viral and antiinflammatory drug called maraviroc, a medicine used in the treatment of HIV infection. Maraviroc works by preventing HIV from entering human immune cells by blocking a protein on the outside of these cells called the C-C chemokine receptor type 5 (CCR5) receptor. When maraviroc is bound to this protein, the virus cannot enter the cell. The investigator thinks that CCR5 antagonists could be particularly good drugs for HIV pre-exposure prophylaxis (PrEP) and could potentially be dosed in ways that are easier to take than the current drugs used for PrEP. In order to further evaluate this PrEP strategy, the investigator will first study the immune cells in the blood and genital tract of HIV-negative healthy female volunteers over the course of 3 months to see how these cells change over time and are affected by factors such as age, menstrual cycle, and genital infections. The amount of maraviroc compared with the drugs in the current drugs used for PrEP (tenofovir/ emtricitabine) in the blood and genital tract of HIV-negative healthy female volunteers before, during, and after they are given maraviroc versus tenofovir/ emtricitabine for 7 days will be measured. We will also study immune cells from the blood and genital tract from these women to see if maraviroc, tenofovir, or emtricitabine have an effect on these cells that would prevent them from becoming infected with HIV.
Interventions
DRUGTruvada qd
Truvada 1 tablet PO daily for 7 days
DRUGMaraviroc 300 qd
Maraviroc 300 mg PO daily for 7 days
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 44 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18-44 years * Must be biologically female (defined as sex at birth) * HIV negative women with at least one of the following risk factors in the past 5 years 1. Injection drug use or use of crack, cocaine, heroin, or methamphetamine 2. Diagnosed with a sexually transmitted infection 3. Unprotected sex with 3 or more men 4. Having sex for drugs, money, or shelter 5. Sex with a known HIV-positive man 6. Having a partner meeting any of the preceding criteria * Normal menses (within 22-35 day intervals) for at least 3 cycles * No history of alcohol abuse, heart disease, or liver disease, or any other medical condition that would interfere with the conduct of the study, in the opinion of the study investigator * No history of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery * Normal chemistry, liver function, and complete blood count panels at screening, including: 1. Absolute neutrophil count (ANC) ≥ 750/mm3 2. Hemoglobin ≥ 10.0 g/dL 3. Platelet count ≥ 100,000/mm3 4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 3 x Upper Limit Normal (ULN) 5. Total bilirubin ≤ 2.5 x ULN 6. Creatinine Clearance (CrCl) ≥ 60 mL/min as estimated by the Cockcroft-Gault equation * Negative hepatitis B surface antigen (HBsAg) * No signs or symptoms of orthostasis * No signs or symptoms of vaginal infection or genital ulcer disease at screening or untreated vaginal infection in the last 30 days * Not receiving concurrent medications that interact with maraviroc (MVC) or any antiretrovirals (such as tenofovir/ emtricitabine \[Truvada®\]) for the purpose of HIV prevention * Willing to use condoms for the duration of the study and abstain from sexual intercourse for 48 hours before each genital tract sampling
Exclusion criteria
* Male sex (defined as sex at birth) * Pregnant or breastfeeding * Current use of systemic hormonal contraception * Symptomatic vaginal infection or genital ulcer disease at screening or treatment for vaginal infection in the last two weeks * Active malignancy for which the participant is undergoing evaluation and/or treatment * Immunosuppressive medications (i.e, systemic steroids) * Any surgery in the preceding 2 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Baseline, Day 7, Day 14, Day 21 | The count of CCR5+CD4+ T cells in the genital tract, before participants began study treatment, after 7 days of treatment, and during the post-treatment drug elimination period. The precise role of CCR5+CD4+ T cells in the female genital tract is unknown, however, higher cell counts may suggest the potential for more HIV target cells in the genital tract. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steady-state Area Under the Plasma Concentration-time Curve of Study Drug | 7 days | Study drug concentrations will be measured from blood. |
| Steady-state Area Under the Female Genital Tract Concentration-time Curve of Study Drug | 7 days | Study drug concentrations will be measured from female genital tract. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Truvada Women randomized to receive one tablet of Truvada (200mg emtricitabine/300mg tenofovir) daily for 7 days. | 1 |
| Maraviroc Women randomized to receive 300mg of Maraviroc daily for 7 days. | 3 |
| Total | 4 |
Baseline characteristics
| Characteristic | Truvada | Maraviroc | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 0 / 1 | 0 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 |
Outcome results
Primary
Count of Total Cells Obtained From Cervicovaginal Lavage Samples
The count of CCR5+CD4+ T cells in the genital tract, before participants began study treatment, after 7 days of treatment, and during the post-treatment drug elimination period. The precise role of CCR5+CD4+ T cells in the female genital tract is unknown, however, higher cell counts may suggest the potential for more HIV target cells in the genital tract.
Time frame: Baseline, Day 7, Day 14, Day 21
Population: The analysis includes all available data collected during each study visit. Not all participants provided a sample at every study visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Truvada | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Day 7 | 15,000,000 cells | Standard Deviation 0 |
| Truvada | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Day 21 | 30,000,000 cells | Standard Deviation 0 |
| Truvada | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Day 14 | 20,000,000 cells | Standard Deviation 0 |
| Truvada | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Baseline | 42,000,000 cells | Standard Deviation 0 |
| Maraviroc | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Day 7 | 18,700,000 cells | — |
| Maraviroc | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Baseline | 20,000,000 cells | Standard Deviation 0 |
| Maraviroc | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Day 14 | 28,300,000 cells | — |
| Maraviroc | Count of Total Cells Obtained From Cervicovaginal Lavage Samples | Day 21 | 21,800,000 cells | — |
Secondary
Steady-state Area Under the Female Genital Tract Concentration-time Curve of Study Drug
Study drug concentrations will be measured from female genital tract.
Time frame: 7 days
Population: Data were not collected at each visit as some participants declined providing samples. Due to the small number of observations, study drug concentrations were not determined for the samples provided.
Secondary
Steady-state Area Under the Plasma Concentration-time Curve of Study Drug
Study drug concentrations will be measured from blood.
Time frame: 7 days
Population: Data were not collected at each visit as some participants declined providing samples. Due to the small number of observations, study drug concentrations were not determined for the samples provided.