HIV-1 Infection
Conditions
Brief summary
This study was done to look at the level of Depo-Provera, an injectable birth control, in the blood to see whether it is affected by the anti-HIV drug Kaletra (lopinavir/ritonavir \[LPV/r\]). It is not known whether taking Depo-Provera together with Kaletra changes the amount of Kaletra in blood. Therefore, this study also looked at the levels of HIV and Kaletra before and after receiving a shot of Depo-Provera. This study evaluated the safety of Depo-Provera and Kaletra when they are used together. In addition to what is stated above, this study also explored any effect of Depo-Provera on the immune system.
Detailed description
The primary study objective was addressed by calculating the Area Under the Concentration-Time Curve (AUC) from week 0 (prior to DMPA injection) to week 12 (twelve weeks after DMPA injection) in our study participants. DMPA was supplied and administered as part of the protocol, however Kaletra was not. It was required that participants already be on a Kaletra based regimen prior to entering the study, as described in the eligibility criteria. Arm A of AIDS Clinical Trial Group (ACTG) A5093, which consisted of 14 participants who were administered DMPA without Kaletra, was used as reference data.
Interventions
At study entry/ Day 0, participants will receive Depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection * Documentation of plasma HIV-1 RNA \</= 400 copies/mL within 30 days prior to study entry. * Last menstrual period \</= 35 days prior to study entry. * If last menstrual period \>35 days prior to study entry, serum follicle-stimulating hormone (FSH) must be \</= 40 Milli-International units per Milliliter (MIU/mL) * Stable anti-retroviral (ARV) regimen consisting of BID LPV/r plus 2 or more nucleoside reverse transcriptase inhibitors (NRTIs) for at least 30 days if postpartum or for at least the previous 14 days if on a previously stable antiretroviral regimen without modifications prior to study entry * Cluster of Differentiation 4 (CD4+) cell count ≥200 cells/mm\^3 within 30 days prior to study entry * Certain laboratory values within 30 days prior to study entry * Premenopausal females with normal ovarian function * Negative serum or urine-Human Chorionic Gonadotropin (HCG) pregnancy test within 72 hours prior to study entry * All subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or in vitro fertilization) for the duration of the study.Subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use an additional reliable method of contraception while in the study. * Ability and willingness to give written informed consent * Documentation of Pap smear within one year prior to study entry. * Documentation of hepatitis B (surface antigen) and hepatitis B (core antibody) and hepatitis C (antibody) status prior to study entry. * Documentation of varicella-zoster virus (VZV) status by history of varicella or herpes zoster, or history of varicella or herpes zoster vaccination or documentation of anti-VZV antibodies. * Willingness to abstain from alcohol 24 hours prior to and during the 10-hour pharmacokinetic (PK) specimen draws. * Willingness to abstain from any grapefruit product or supplement for 24 hours prior to entry and for the duration of the study.
Exclusion criteria
* Received DMPA within 180 days prior to study entry. * Received other hormonal therapies within the 30 days prior to study entry. * Concurrent dual nucleoside therapy of zidovudine (ZDV) and stavudine (d4T) within 30 days prior to study entry. * Use of any prohibited medications within 30 days prior to study entry. Prohibited Medications were: * amiodarone (Cordarone) * astemizole (Hismanal) * bepridil (Vascor) * carbamazepine (Tegretol) * cisapride (Propulsid) * clarithromycin (Biaxin) * cyclosporine (Sandimmune, Neoral) * dihydroergotamine (Migranal and others) * ergotamine (Ergostat, Gotamine, and others) * erythromycin (E-mycin, erythromycin ethylsuccinate (EES) and others) * flecainide (Tambocor) * glucocorticoids * Hypericum perforatum (St. John's wort) * itraconazole (Sporanox) * ketoconazole (Nizoral) * lovastatin (Mevacor) * midazolam (Versed) * nefazadone (Serzone) * phenobarbital (Luminal) * phenytoin (Dilantin) * pimozide (Orap) * pioglitazone (Actos) * propafenone (Rythmol) * propofol (Diprivan) * quinidine (Quinidex) * rifabutin (Mycobutin) * rifampin (Rifadin, Rifamate, Rifater, Rimactane) * rosiglitazone (Avandia) * simvastatin (Zocor) * tacrolimus (Prograf) * terfenadine * ticlopidine (Ticlid), and * triazolam (Halcion) * Breastfeeding. * Less than 30 days postpartum at study entry. * Bilateral oophorectomy. * Hypersensitivity to DMPA, MPA, or any of the other ingredients in DMPA. * More than a 50% change in tobacco smoking within the 30 days prior to study entry or plans to significantly change tobacco use during the study. * Invasive cancer of the reproductive tract; known or suspected malignancy of the breast, or known increased risk for breast cancer; undiagnosed vaginal bleeding; liver tumors; or serious ocular disorders at any time prior to study entry. * Uncontrolled hypothyroidism or hyperthyroidism within 30 days of study entry. * Acute infections or other opportunistic diseases requiring medication within 14 days prior to study entry. * Receipt of any immunizations within 2 weeks prior to enrollment. * Use of any immunosuppressant medication including systemic corticosteroids within 30 days prior to study entry. * Chronic immunosuppressive conditions other than HIV. * Initiated, discontinued, or changed doses of drugs that are cytochrome P450 3A4 (CYP3A4) substrates within 30 days of study entry. * History of deep venous thrombosis or pulmonary emboli.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medroxyprogesterone Acetate (MPA) Pharmacokinetic Parameter (PK) Area Under the Concentration-time Curve (AUC0-12weeks) | Day 0, Weeks 2, 4, 6, 8, 10 and 12 | This evaluates the effect of lopinavir/ritonavir (LPV/r) on pharmacokinetic parameter AUC of MPA by looking at the MPA AUC from day 0 to week 12. AUC0-12weeks was calculated using single MPA concentrations sampled immediately prior to DMPA administration on day 0, and at 2, 4, 6, 8, 10 and 12 weeks after administration of the single DMPA dose. |
| AUC0-12hour for LPV at Baseline (Day 0) Before DMPA Administration and at Week 4 (Four Weeks After DMPA Administration) | Day 0 and Week 4 | This evaluates the effect of DMPA on LPV PK parameter AUC by comparing PK AUCs of LPV from 0 to 12 hours obtained at study Day 0 (before DMPA was administered) with PK AUCs of LPV from 0 to 12 hours at study Week 4 (4 weeks after DMPA was administered). Blood samples were drawn for LPV concentration levels at time zero (before LPV/r dosing) and at 30 minutes and 1, 2, 3, 4, 5, 6, 8 and 10 hours after LPV/r dosing at day 0 and week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MPA PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on MPA Levels. | 0, 2, 4, 6, 8, 10, and 12 weeks | This evaluates the effect of LPV/r on the secondary MPA PK parameter Cmin based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12. |
| MPA PK Parameter Time to Cmax (Tmax) Determined Based on MPA Levels. | 0, 2, 4, 6, 8, 10, and 12 weeks | This evaluates the effect of LPV/r on the secondary MPA PK parameter Tmax based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12. |
| MPA PK Parameter Clearance (CL/F) Determined Based on MPA Levels. | 0, 2, 4, 6, 8, 10, and 12 weeks | This evaluates the effect of LPV/r on the secondary MPA PK parameter CL/F based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12. |
| MPA PK Parameter Half-Life (T1/2) Determined Based on MPA Levels. | 0, 2, 4, 6, 8, 10, and 12 weeks | This evaluates the effect of LPV/r on the secondary MPA PK parameter T1/2 based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12. |
| LPV PK Parameter Cmin. | Day 0 and Week 4 | This evaluates the effect of MPA on the secondary LPV PK parameter Cmin obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4. |
| LPV PK Parameter Cmax. | Day 0 and Week 4 | This evaluates the effect of MPA on the secondary LPV PK parameter Cmax obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4. |
| LPV PK Parameter Tmax. | Day 0 and Week 4 | This evaluates the effect of MPA on the secondary LPV PK parameter Tmax obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4. |
| LPV PK Parameter CL/F. | Day 0 and Week 4 | This evaluates the effect of MPA on the secondary LPV PK parameter CL/F obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4. |
| LPV PK Parameter T1/2. | Day 0 and Week 4 | This evaluates the effect of MPA on the secondary LPV PK parameter T1/2 obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4. |
| Ritonavir (RTV) PK Parameter AUC0-12h. | Day 0 and Week 4 | This evaluates the effect of MPA on the PK parameter AUC0-12h of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. Blood samples were drawn for RTV concentration levels at time zero (before LPV/r dosing) and at 30 minutes and 1, 2, 3, 4, 5, 6, 8 and 10 hours after LPV/r dosing at day 0 and week 4. |
| MPA PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on MPA Levels. | 0, 2, 4, 6, 8, 10, and 12 weeks | This evaluates the effect of LPV/r on the secondary MPA PK parameter Cmax based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12. |
| RTV PK Parameter Cmax. | Day 0 and Week 4 | This evaluates the effect of MPA on the PK parameter Cmax of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. |
| RTV PK Parameter Tmax. | Day 0 and Week 4 | This evaluates the effect of MPA on the PK parameter Tmax of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. |
| RTV PK Parameter CL/F. | Day 0 and Week 4 | This evaluates the effect of MPA on the PK parameter CL/F of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. |
| RTV PK Parameter T1/2. | Day 0 and Week 4 | This evaluates the effect of MPA on the PK parameter T1/2 of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. |
| Percentage of Participants With Menstrual Irregularities of Grade 1 and Higher Deemed Possibly, Probably or Definitely Related to Study Treatment. | From day 0 to week 12 | This evaluates toxicity and safety of concomitant medication of DMPA and LPV/r, focusing specifically on the adverse event (AE) menstrual irregularities with abnormal vaginal bleeding. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the study's co-chairs. |
| Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL. | Day 0, Weeks 2, 4, 8, and 12 | This evaluates the short-term impact of MPA on virologic suppression in participants taking LPV/r who have received a dose of DMPA by measuring percentage of participants with HIV-1 RNA levels \<400 copies/mL at day 0 (prior to DMPA injection) and at weeks 2, 4, 8 and 12 (after DMPA injection). An FDA-approved HIV-1 RNA assay with a lower limit of detection of 75 copies/mL or less was required and the same HIV-1 RNA assay was required to be performed for each participant across all study visits. The Roche COBAS AmpliPrep/TaqMan HIV-1 and Abbott RealTime HIV-1 tests were used. |
| Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | Day 0, Weeks 4 and 12 | This evaluates the effect of MPA on CMI to HIV and VZV at baseline before DMPA (day 0) and after DMPA (weeks 4 and 12) . Cytokines are interferon-gamma (IFN-gamma) and interleukin 2 (IL-2), and Stimuli are HIV and VZV. Summary of adjusted ELISPOT assay results is in spot forming cells (SFC)/10\^6 peripheral blood mononuclear cells (PBMC) by study weeks 0, 4 and 12. The outcome measures of IFN-gamma and IL-2 measured for HIV and VZV are presented here together to provide all results pertaining to the same objective in a single data table. |
| CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | Day 0, Weeks 4 and 12 | This evaluates the effect of MPA on CMI to HIV and VZV. This outcome was measured at Baseline Before DMPA (Day 0) and After DMPA (Weeks 4 and 12) using the Lymphocyte Proliferation Assay (LPA). The data table shows a summary of LPA assay results by study week with stimuli HIV and VZV. Proliferation results are reported as a stimulation index (SI) which represents the ratio of the stimulated counts per minute to unstimulated control counts per minute. |
| Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | Day 0, Weeks 4 and 12 | This evaluates the effect of MPA on Tregs at baseline (Day 0), week 4 and week 12 using flow cytometry in freshly thawed PBMCs. A summary of CD4+ and cluster of differentiation 8 (CD8+) anchored T-cell subsets by study week, in percent that express the marker of interest, is presented here together to provide all results pertaining to this objective in a single data table. |
| RTV PK Parameter Cmin. | Day 0 and Week 4 | This evaluates the effect of MPA on the PK parameter Cmin of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. |
| Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | 0, 2, 4, 6, 8, 10, and 12 weeks | This evaluates the suppression of ovulation due to the potential PK interaction between DMPA and LPV/r. The LLQ of progesterone is 0.5ng/mL. The threshold for suppression of ovulation is 5ng/mL. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Twenty-five HIV-1 infected women, ages 15 to 47 years, were recruited at 13 U.S. Clinical Research Sites and U.S. National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development-funded International Maternal Pediatric Adolescent AIDS Clinical Trial sites between June 1, 2011 and July 26, 2012.
Pre-assignment details
Eligible participants: pre-menopausal HIV-1 infected females, \>=13 years, plasma HIV-1 RNA \<=400 copies/mL and cluster of differentiation 4 (CD4+) count \>= 200 cells/mm\^3 within 30 days prior to entry. Last menstrual period \<=35 days prior to entry. If \>35 days, follicle stimulating hormone (FSH) must have been \<=40 Milli-International units/mL.
Participants by arm
| Arm | Count |
|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) At study entry/ Day 0, subjects will receive depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
depo-medroxyprogesterone acetate: At study entry/ Day 0, participants will receive Depo-medroxyprogesterone (DMPA) 150mg administered intramuscularly (IM) as a single-dose.
Depo-medroxyprogesterone Acetate | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unwilling to adhere to study requirement | 1 |
Baseline characteristics
| Characteristic | Depo-medroxyprogesterone Acetate (DMPA) |
|---|---|
| Age, Categorical <=18 years | 3 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 31 years |
| Race/Ethnicity, Customized American Indian, Alaskan Native | 1 participants |
| Race/Ethnicity, Customized Black Non-Hispanic | 15 participants |
| Race/Ethnicity, Customized Hispanic (Regardless of Race) | 6 participants |
| Race/Ethnicity, Customized White Non-Hispanic | 3 participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
AUC0-12hour for LPV at Baseline (Day 0) Before DMPA Administration and at Week 4 (Four Weeks After DMPA Administration)
This evaluates the effect of DMPA on LPV PK parameter AUC by comparing PK AUCs of LPV from 0 to 12 hours obtained at study Day 0 (before DMPA was administered) with PK AUCs of LPV from 0 to 12 hours at study Week 4 (4 weeks after DMPA was administered). Blood samples were drawn for LPV concentration levels at time zero (before LPV/r dosing) and at 30 minutes and 1, 2, 3, 4, 5, 6, 8 and 10 hours after LPV/r dosing at day 0 and week 4.
Time frame: Day 0 and Week 4
Population: All participants eligible for the first primary PK outcome measure (MPA AUC0-12weeks) were included in this second primary outcome measure looking at LPV AUC0-12hours at Day 0 and week 4.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | AUC0-12hour for LPV at Baseline (Day 0) Before DMPA Administration and at Week 4 (Four Weeks After DMPA Administration) | LPV AUC0-12hour at day 0 (without DMPA) | 98046.46 ng*h/mL |
| Depo-medroxyprogesterone Acetate (DMPA) | AUC0-12hour for LPV at Baseline (Day 0) Before DMPA Administration and at Week 4 (Four Weeks After DMPA Administration) | LPV AUC0-12hour at week 4 (with DMPA) | 97948.29 ng*h/mL |
Primary
Medroxyprogesterone Acetate (MPA) Pharmacokinetic Parameter (PK) Area Under the Concentration-time Curve (AUC0-12weeks)
This evaluates the effect of lopinavir/ritonavir (LPV/r) on pharmacokinetic parameter AUC of MPA by looking at the MPA AUC from day 0 to week 12. AUC0-12weeks was calculated using single MPA concentrations sampled immediately prior to DMPA administration on day 0, and at 2, 4, 6, 8, 10 and 12 weeks after administration of the single DMPA dose.
Time frame: Day 0, Weeks 2, 4, 6, 8, 10 and 12
Population: One participant was excluded from all PK analyses for taking a prohibited medication with potential to interfere with PK assessments. For another participant who missed week 10 and 12 visits, a modelling approach was used to estimate the week 12 MPA level.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Medroxyprogesterone Acetate (MPA) Pharmacokinetic Parameter (PK) Area Under the Concentration-time Curve (AUC0-12weeks) | 18.08 ng*wk/mL |
Secondary
Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay.
This evaluates the effect of MPA on CMI to HIV and VZV at baseline before DMPA (day 0) and after DMPA (weeks 4 and 12) . Cytokines are interferon-gamma (IFN-gamma) and interleukin 2 (IL-2), and Stimuli are HIV and VZV. Summary of adjusted ELISPOT assay results is in spot forming cells (SFC)/10\^6 peripheral blood mononuclear cells (PBMC) by study weeks 0, 4 and 12. The outcome measures of IFN-gamma and IL-2 measured for HIV and VZV are presented here together to provide all results pertaining to the same objective in a single data table.
Time frame: Day 0, Weeks 4 and 12
Population: All 24 participants included in the primary analyses were eligible for this secondary objective. 22 participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IFN-gamma*HIV Week 12 (N=20) | 57.75 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IFN-gamma*VZV Week 0 (N=20) | 2.75 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IFN-gamma*VZV Week 4 (N=20) | 2.00 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IFN-gamma*VZV Week 12 (N=19) | 6.50 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IL-2*HIV Week 0 (N=22) | 5.00 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IL-2*HIV Week 4 (N=21) | 4.50 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IL-2*HIV Week 12 (N=20) | 1.75 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IL-2*VZV Week 0 (N=20) | 3.25 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IL-2*VZV Week 4 (N=20) | 2.50 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IFN-gamma*HIV Week 0 (N=22) | 82.50 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IFN-gamma*HIV Week 4 (N=21) | 46.50 SFC/10^6 PBMC |
| Depo-medroxyprogesterone Acetate (DMPA) | Cell Mediated Immunity (CMI) to HIV and the Common Opportunistic Agent Varicella-zoster Virus (VZV) Using the Enzyme-linked Immunospot (ELISPOT) Assay. | IL-2*VZV Week 12 (N=19) | 5.50 SFC/10^6 PBMC |
Secondary
CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA).
This evaluates the effect of MPA on CMI to HIV and VZV. This outcome was measured at Baseline Before DMPA (Day 0) and After DMPA (Weeks 4 and 12) using the Lymphocyte Proliferation Assay (LPA). The data table shows a summary of LPA assay results by study week with stimuli HIV and VZV. Proliferation results are reported as a stimulation index (SI) which represents the ratio of the stimulated counts per minute to unstimulated control counts per minute.
Time frame: Day 0, Weeks 4 and 12
Population: All 24 participants included in the primary analyses were eligible for this secondary objective. 22 participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | HIV SI Week 4 (N=17) | 21.39 SI Ratio |
| Depo-medroxyprogesterone Acetate (DMPA) | CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | HIV SI Week 12 (N=14) | 54.66 SI Ratio |
| Depo-medroxyprogesterone Acetate (DMPA) | CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | VZV SI Week 0 (N=22) | 22.38 SI Ratio |
| Depo-medroxyprogesterone Acetate (DMPA) | CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | VZV SI Week 4 (N=22) | 17.73 SI Ratio |
| Depo-medroxyprogesterone Acetate (DMPA) | CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | VZV SI Week 12 (N=21) | 23.28 SI Ratio |
| Depo-medroxyprogesterone Acetate (DMPA) | CMI to HIV and the Common Opportunistic Agent VZV Using the Lymphocyte Proliferation Assay (LPA). | HIV SI Week 0 (N=18) | 50.62 SI Ratio |
Secondary
LPV PK Parameter CL/F.
This evaluates the effect of MPA on the secondary LPV PK parameter CL/F obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter CL/F. | LPV CL/F week 4 | 4.08 L/hour |
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter CL/F. | LPV CL/F day 0 | 4.08 L/hour |
Secondary
LPV PK Parameter Cmax.
This evaluates the effect of MPA on the secondary LPV PK parameter Cmax obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter Cmax. | LPV Cmax day 0 | 10750.00 ng/mL |
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter Cmax. | LPV Cmax week 4 | 10950.00 ng/mL |
Secondary
LPV PK Parameter Cmin.
This evaluates the effect of MPA on the secondary LPV PK parameter Cmin obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter Cmin. | LPV Cmin day 0 | 5630.00 ng/mL |
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter Cmin. | LPV Cmin week 4 | 5700.00 ng/mL |
Secondary
LPV PK Parameter T1/2.
This evaluates the effect of MPA on the secondary LPV PK parameter T1/2 obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter T1/2. | LPV T1/2 week 4 | 12.64 hour |
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter T1/2. | LPV T1/2 day 0 | 11.76 hour |
Secondary
LPV PK Parameter Tmax.
This evaluates the effect of MPA on the secondary LPV PK parameter Tmax obtained from both sampling periods, before DMPA injection at study day 0 and four weeks after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter Tmax. | LPV Tmax day 0 | 3.00 hour |
| Depo-medroxyprogesterone Acetate (DMPA) | LPV PK Parameter Tmax. | LPV Tmax week 4 | 3.00 hour |
Secondary
MPA PK Parameter Clearance (CL/F) Determined Based on MPA Levels.
This evaluates the effect of LPV/r on the secondary MPA PK parameter CL/F based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.
Time frame: 0, 2, 4, 6, 8, 10, and 12 weeks
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of MPA AUC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | MPA PK Parameter Clearance (CL/F) Determined Based on MPA Levels. | 8297.35 L/week |
Secondary
MPA PK Parameter Half-Life (T1/2) Determined Based on MPA Levels.
This evaluates the effect of LPV/r on the secondary MPA PK parameter T1/2 based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.
Time frame: 0, 2, 4, 6, 8, 10, and 12 weeks
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of MPA AUC. A minimum of three observations in the elimination phase was required to determine T1/2 and therefore results are presented for 22 participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | MPA PK Parameter Half-Life (T1/2) Determined Based on MPA Levels. | 3.37 week |
Secondary
MPA PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on MPA Levels.
This evaluates the effect of LPV/r on the secondary MPA PK parameter Cmax based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.
Time frame: 0, 2, 4, 6, 8, 10, and 12 weeks
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of MPA AUC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | MPA PK Parameter Maximum Plasma Concentration (Cmax) Determined Based on MPA Levels. | 2.88 ng/mL |
Secondary
MPA PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on MPA Levels.
This evaluates the effect of LPV/r on the secondary MPA PK parameter Cmin based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.
Time frame: 0, 2, 4, 6, 8, 10, and 12 weeks
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of MPA AUC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | MPA PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on MPA Levels. | 0.47 ng/mL |
Secondary
MPA PK Parameter Time to Cmax (Tmax) Determined Based on MPA Levels.
This evaluates the effect of LPV/r on the secondary MPA PK parameter Tmax based on MPA levels measured at weeks 0, 2, 4, 6, 8, 10, and 12.
Time frame: 0, 2, 4, 6, 8, 10, and 12 weeks
Population: The analysis population is the 24 A5283 participants who took DMPA with LPV/r and were eligible for the primary PK outcome of MPA AUC.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | MPA PK Parameter Time to Cmax (Tmax) Determined Based on MPA Levels. | 4.00 week |
Secondary
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL.
This evaluates the short-term impact of MPA on virologic suppression in participants taking LPV/r who have received a dose of DMPA by measuring percentage of participants with HIV-1 RNA levels \<400 copies/mL at day 0 (prior to DMPA injection) and at weeks 2, 4, 8 and 12 (after DMPA injection). An FDA-approved HIV-1 RNA assay with a lower limit of detection of 75 copies/mL or less was required and the same HIV-1 RNA assay was required to be performed for each participant across all study visits. The Roche COBAS AmpliPrep/TaqMan HIV-1 and Abbott RealTime HIV-1 tests were used.
Time frame: Day 0, Weeks 2, 4, 8, and 12
Population: All 24 participants included in the primary analyses were eligible for this secondary objective, however participants occasionally missed the HIV-1 RNA draw (see N for each week in table below).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL. | Pct with HIV RNA<400 at Week 0 (N=24) | 100 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL. | Pct with HIV RNA<400 at Week 2 (N=24) | 100 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL. | Pct with HIV RNA<400 at Week 4 (N=23) | 100 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL. | Pct with HIV RNA<400 at Week 8 (N=24) | 100 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL. | Pct with HIV RNA<400 at Week 12 (N=23) | 87 Percent of Participants |
Secondary
Percentage of Participants With Menstrual Irregularities of Grade 1 and Higher Deemed Possibly, Probably or Definitely Related to Study Treatment.
This evaluates toxicity and safety of concomitant medication of DMPA and LPV/r, focusing specifically on the adverse event (AE) menstrual irregularities with abnormal vaginal bleeding. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see references in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening, Grade 5=Death. Relationship to study treatment was determined by the study's co-chairs.
Time frame: From day 0 to week 12
Population: This analysis focuses on the 24 participants eligible for the PK analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Menstrual Irregularities of Grade 1 and Higher Deemed Possibly, Probably or Definitely Related to Study Treatment. | 25 Percent of Participants |
Secondary
Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ).
This evaluates the suppression of ovulation due to the potential PK interaction between DMPA and LPV/r. The LLQ of progesterone is 0.5ng/mL. The threshold for suppression of ovulation is 5ng/mL.
Time frame: 0, 2, 4, 6, 8, 10, and 12 weeks
Population: All 24 participants included in the primary analyses were eligible for this secondary objective, however participants occasionally missed the progesterone draw (see N for each week in table below).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 0 (N=24) | 50.0 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 2 (N=23) | 87.0 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 4 (N=24) | 95.8 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 6 (N=24) | 95.8 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 8 (N=24) | 95.8 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 10 (N=20) | 95.0 Percent of Participants |
| Depo-medroxyprogesterone Acetate (DMPA) | Percentage of Participants With Progesterone Levels Less Than the Lower Limit of Quantification (LLQ). | Pct with Progesterone<LLQ at Week 12 (N=23) | 95.7 Percent of Participants |
Secondary
Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs.
This evaluates the effect of MPA on Tregs at baseline (Day 0), week 4 and week 12 using flow cytometry in freshly thawed PBMCs. A summary of CD4+ and cluster of differentiation 8 (CD8+) anchored T-cell subsets by study week, in percent that express the marker of interest, is presented here together to provide all results pertaining to this objective in a single data table.
Time frame: Day 0, Weeks 4 and 12
Population: All 24 participants included in the primary analyses were eligible for this secondary objective. 21 participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+FOXP3+ Week 0 | 1.26 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+FOXP3+ Week 4 | 1.30 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+FOXP3+ Week 12 | 1.29 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+CD39+ Week 0 | 10.10 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+CD39+ Week 4 | 10.10 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+CD39+ Week 12 | 11.60 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+TGFB+ Week 12 | 3.08 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+IL10+ Week 0 | 4.66 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+IL10+ Week 4 | 6.01 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+IL10+ Week 12 | 5.64 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+IL35+ Week 0 | 1.86 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+FOXP3+ Week 4 | 0.91 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+FOXP3+ Week 12 | 0.74 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+CD25+FOXP3+ Week 0 | 0.07 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+CD25+FOXP3+ Week 4 | 0.06 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+CD25+FOXP3+ Week 12 | 0.08 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+CD39+ Week 0 | 3.38 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+CD39+ Week 12 | 3.12 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+IL35+ Week 12 | 0.89 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+CD25+FOXP3+ Week 0 | 0.41 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+CD25+FOXP3+ Week 4 | 0.24 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+CD25+FOXP3+ Week 12 | 0.33 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+TGFB+ Week 0 | 4.32 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+TGFB+ Week 4 | 3.62 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+Interleukin35+(IL35+) Week 4 | 1.59 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD4+IL35+ Week 12 | 1.35 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+FOXP3+ Week 0 | 0.85 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+CD39+ Week 4 | 4.20 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+TGFB+ Week 0 | 1.26 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+TGFB+ Week 4 | 1.22 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+TGFB+ Week 12 | 1.18 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+IL10+ Week 0 | 1.46 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+IL10+ Week 4 | 1.53 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+IL10+ Week 12 | 1.45 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+IL35+ Week 0 | 1.22 Percent CD4/CD8 cells expressing marker |
| Depo-medroxyprogesterone Acetate (DMPA) | Regulatory T Cells (Tregs) at Baseline, Week 4 and Week 12 Using Flow Cytometry in Freshly Thawed PBMCs. | CD8+IL35+ Week 4 | 1.52 Percent CD4/CD8 cells expressing marker |
Secondary
Ritonavir (RTV) PK Parameter AUC0-12h.
This evaluates the effect of MPA on the PK parameter AUC0-12h of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4. Blood samples were drawn for RTV concentration levels at time zero (before LPV/r dosing) and at 30 minutes and 1, 2, 3, 4, 5, 6, 8 and 10 hours after LPV/r dosing at day 0 and week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | Ritonavir (RTV) PK Parameter AUC0-12h. | RTV AUC0-12h day 0 | 5176.79 ng*h/mL |
| Depo-medroxyprogesterone Acetate (DMPA) | Ritonavir (RTV) PK Parameter AUC0-12h. | RTV AUC0-12h week 4 | 5014.73 ng*h/mL |
Secondary
RTV PK Parameter CL/F.
This evaluates the effect of MPA on the PK parameter CL/F of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter CL/F. | RTV CL/F week 4 | 19.94 L/hour |
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter CL/F. | RTV CL/F day 0 | 19.32 L/hour |
Secondary
RTV PK Parameter Cmax.
This evaluates the effect of MPA on the PK parameter Cmax of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter Cmax. | RTV Cmax day 0 | 884.00 ng/mL |
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter Cmax. | RTV Cmax week 4 | 726.00 ng/mL |
Secondary
RTV PK Parameter Cmin.
This evaluates the effect of MPA on the PK parameter Cmin of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter Cmin. | RTV Cmin day 0 | 181.00 ng/mL |
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter Cmin. | RTV Cmin week 4 | 194.50 ng/mL |
Secondary
RTV PK Parameter T1/2.
This evaluates the effect of MPA on the PK parameter T1/2 of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants eligible for the primary PK outcome of LPV AUC. For one participant at day 0, T1/2 results were not estimated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter T1/2. | RTV T1/2 day 0 (N=23) | 4.56 hour |
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter T1/2. | RTV T1/2 week 4 | 6.32 hour |
Secondary
RTV PK Parameter Tmax.
This evaluates the effect of MPA on the PK parameter Tmax of RTV obtained from both sampling periods, before DMPA injection at study day 0 and after DMPA injection at study week 4.
Time frame: Day 0 and Week 4
Population: The analysis population is the 24 A5283 participants eligible for the primary PK outcome of LPV AUC.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter Tmax. | RTV Tmax day 0 | 3.00 hour |
| Depo-medroxyprogesterone Acetate (DMPA) | RTV PK Parameter Tmax. | RTV Tmax week 4 | 3.00 hour |