Women's HealthNCT01456962
Influence of Antiretroviral Regimen on Immune Reconstitution in the Female Genital Tract
An observational study of Women's Health and HIV Infection, run by University of Colorado, Denver at 1 site in United States.
Trial summary
Increases in cluster of differentiation 4 (CD4)+ T cells in the blood is well documented in human immunodeficiency virus (HIV)-infected individuals after starting antiretroviral therapy (ART), but increases CD4+ T cells in the cervix is variable and not fully understood. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Women's Health, HIV Infection, Genital Diseases, Female
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Aug 2013
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) compared to tenofovir (TDF) and emtricitabine (FTC) and ritonavir (RIT)-boosted atazanavir (ATZ)
Who may be able to join
- HIV-1 seropositive women receiving a RAL-based regimen (n=20) and women receiving an atazanavir-based regimen (n=20).
- Women will be recruited to this study from the Denver metropolitan area.
- The women must have a plasma HIV RNA <48 copies/mL for at least 6 months on the same antiretroviral regimen, and a CD4+ T cell count > 300 cell/mm3.
- Transient increases of <=200 copies HIV-1 RNA copies/ mL will be allowed.
Who cannot join
- Hysterectomy
- No a menstrual cycle for 12 months
- Active substance abuse
- hematocrit (HCT) <30
- Bleeding diathesis
- Known carcinoma of the cervix
- Using oral glucocorticoids or other immunosuppressive agents
- Current pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Raltegravir-Containing Antiretroviral Therapy (ART) on Immune Reconstitution and Activation in the Female Genital Tract
Increases in cluster of differentiation 4 (CD4)+ T cells in the blood is well documented in human immunodeficiency virus (HIV)-infected individuals after starting antiretroviral therapy (ART), but increases CD4+ T cells in the cervix is variable and not fully understood. Although the amount of HIV in the vagina declines in parallel with those in the plasma when antiretroviral therapy for HIV is started, HIV is still detected frequently in cervical samples from women with undetectable plasma viral loads, suggesting that low level viral replication in the female vaginal tract could lead to both inflammation and incomplete increases in CD4+ T cells. Two classes of HIV medications, nonnucleoside analogue reverse transcriptase inhibitors and protease inhibitors are substantially lower in the female genital tract compared to plasma, whereas concentrations of another class, nucleos(t)ide analogue reverse transcriptase inhibitors are similar or higher to those found in plasma. Thus, many widely used first-line three drug HIV therapies only achieve high concentrations of only two medications in the female genital tract. Importantly, with the recent development of raltegravir (RAL), which achieves concentrations in the female genital tract higher than those in plasma, ART regimens that deliver high concentrations of 3 antiretroviral drugs to the female genital tract are now available. The investigators hypothesize that cervical CD4+ T cell reconstitution is better and inflammatory markers are lower in HIV-infected women on a HIV-therapy including tenofovir (TDF) and emtricitabine (FTC) with RAL versus ritonavir (RIT)-boosted atazanavir (ATZ), and that this is due to therapeutic concentrations of 3 versus 2 antiretroviral drugs in the female genital tract.
- Conditions
- Women's Health, HIV Infection, Genital Diseases, Female
- Keywords
- Immune reconstitution, CD4+ T cells
- Medical subject headings
- HIV Infections, Genital Diseases, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Raltegravir group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) | |
| Atazanavir group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ to CD8+ T Cell Ratio in Cervical Biopsies
Evaluation of cervical immune health in HIV-infected women on tenofovir (TDF) and emtricitabine (FTC) and either raltegravir or atazanavir. Cervical CD4+ to CD8+ T cell ratios will be measured at one time point from cervical biopsies. Higher ratios will be a measure of better cervical immune health. In addition, ratios will be compared to the concentration of the drug in the genital tract.
Measured: 12 hours after the last medication dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Women's HealthStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01456962
- Sponsor's protocol ID
- 11-1265
- Other IDs
- 39423
- Status last verified
- May 2017
- First submitted
- 6 Oct 2011
- Last updated
- 9 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Meditz AL, Palmer C, Predhomme J, Searls K, Kerr B, Seifert S, Caraway P, Gardner EM, MaWhinney S, Anderson PL. Relationship Between Genital Drug Concentrations and Cervical Cellular Immune Activation and Reconstitution in HIV-1-Infected Women on a Raltegravir Versus a Boosted Atazanavir Regimen. AIDS Res Hum Retroviruses. 2015 Oct;31(10):1015-22. doi: 10.1089/AID.2014.0301. Epub 2015 Jun 10.
PubMed 26059647
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Raltegravir-Containing Antiretroviral Therapy (ART) on Immune Reconstitution and Activation in the Female Genital Tract
- ClinicalTrials.gov ID
- NCT01456962
- Acronym / sponsor ID
- 11-1265
- Conditions
- Women's Health, HIV Infection, Genital Diseases, Female
- Keywords
- Immune reconstitution, CD4+ T cells
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Oct 2011 (actual)
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 21 Oct 2011 (estimated)
- Results
- Posted 12 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Increases in cluster of differentiation 4 (CD4)+ T cells in the blood is well documented in human immunodeficiency virus (HIV)-infected individuals after starting antiretroviral therapy (ART), but increases CD4+ T cells in the cervix is variable and not fully understood. Although the amount of HIV in the vagina declines in parallel with those in the plasma when antiretroviral therapy for HIV is started, HIV is still detected frequently in cervical samples from women with undetectable plasma viral loads, suggesting that low level viral replication in the female vaginal tract could lead to both inflammation and incomplete increases in CD4+ T cells. Two classes of HIV medications, nonnucleoside analogue reverse transcriptase inhibitors and protease inhibitors are substantially lower in the female genital tract compared to plasma, whereas concentrations of another class, nucleos(t)ide analogue reverse transcriptase inhibitors are similar or higher to those found in plasma. Thus, many widely used first-line three drug HIV therapies only achieve high concentrations of only two medications in the female genital tract. Importantly, with the recent development of raltegravir (RAL), which achieves concentrations in the female genital tract higher than those in plasma, ART regimens that deliver high concentrations of 3 antiretroviral drugs to the female genital tract are now available. The investigators hypothesize that cervical CD4+ T cell reconstitution is better and inflammatory markers are lower in HIV-infected women on a HIV-therapy including tenofovir (TDF) and emtricitabine (FTC) with RAL versus ritonavir (RIT)-boosted atazanavir (ATZ), and that this is due to therapeutic concentrations of 3 versus 2 antiretroviral drugs in the female genital tract.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Raltegravir group | – | –HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) |
| Atazanavir group | – | –HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) compared to tenofovir (TDF) and emtricitabine (FTC) and ritonavir (RIT)-boosted atazanavir (ATZ)
Key inclusion criteria (4 listed)
- HIV-1 seropositive women receiving a RAL-based regimen (n=20) and women receiving an atazanavir-based regimen (n=20).
- Women will be recruited to this study from the Denver metropolitan area.
- The women must have a plasma HIV RNA <48 copies/mL for at least 6 months on the same antiretroviral regimen, and a CD4+ T cell count > 300 cell/mm3.
- Transient increases of <=200 copies HIV-1 RNA copies/ mL will be allowed.
Key exclusion criteria (8 listed)
- Hysterectomy
- No a menstrual cycle for 12 months
- Active substance abuse
- hematocrit (HCT) <30
- Bleeding diathesis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
CD4+ to CD8+ T Cell Ratio in Cervical Biopsies
Time frame: 12 hours after the last medication dose
Evaluation of cervical immune health in HIV-infected women on tenofovir (TDF) and emtricitabine (FTC) and either raltegravir or atazanavir. Cervical CD4+ to CD8+ T cell ratios will be measured at one time point from cervical biopsies. Higher ratios will be a measure of better cervical immune health. In addition, ratios will be compared to the concentration of the drug in the genital tract.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26059647Meditz AL, Palmer C, Predhomme J, Searls K, Kerr B, Seifert S, Caraway P, Gardner EM, MaWhinney S, Anderson PL. Relationship Between Genital Drug Concentrations and Cervical Cellular Immune Activation and Reconstitution in HIV-1-Infected Women on a Raltegravir Versus a Boosted Atazanavir Regimen. AIDS Res Hum Retroviruses. 2015 Oct;31(10):1015-22. doi: 10.1089/AID.2014.0301. Epub 2015 Jun 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Women's Health and HIV Infection, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CD4+ to CD8+ T Cell Ratio in Cervical Biopsies (time frame: 12 hours after the last medication dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01456962, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2017.