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| ID | Type | Description | Link |
|---|---|---|---|
| 39423 | Other Grant/Funding Number | Merck |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 12 hours after the last medication dose |
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Inclusion Criteria:
Exclusion Criteria:
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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)
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26059647 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Raltegravir Group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) with a CD4+ T-cells/mm3 >300 and HIV RNA copies/mL <48 for a minimum of 6 months. |
| FG001 | Atazanavir Group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ) with a CD4+ T-cells/mm3 >300 and HIV RNA copies/mL <48 for a minimum of 6 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Raltegravir Group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) with a CD4+ T-cells/mm3 >300 and HIV RNA copies/mL <48 for a minimum of 6 months. |
| BG001 | Atazanavir Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Geometric Mean | 95% Confidence Interval | Cervical CD4+:CD8+ T cell ratio | 12 hours after the last medication dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Raltegravir Group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with raltegravir (RAL) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter Anderson, Pharm D | University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences | 303-724-6128 | peter.anderson@ucdenver.edu |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D005831 | Genital Diseases, Female |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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Blood, vaginal fluid samples, cervical biopsies
HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ) with a CD4+ T-cells/mm3 >300 and HIV RNA copies/mL <48 for a minimum of 6 months.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ)
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Atazanavir Group | HIV-1-infected women on a regimen of tenofovir (TDF) and emtricitabine (FTC) with ritonavir (RIT)-boosted atazanavir (ATZ) | 0 | 19 | 0 | 19 |
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| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |