PRIDE-HT: PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB

• Sponsor: AIDS Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT02412436
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 62
• Locations: 5
• Arm: 1
• Actual Duration (Months): 19.4
• Patients Per Site: 12.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study was done to evaluate the effect of HIV and TB treatment on a commonly used birth control method. It enrolled women who were infected with HIV and TB and were taking efavirenz (EFV; Sustiva®; an anti-HIV medication), rifampicin (RIF; an anti-TB medication), and isoniazid (INH; an anti-TB medication). The purpose of this study was to find out the best frequency to give depot medroxyprogesterone acetate (DMPA; a hormonal birth control method that is given as a shot every 3 months) in these women. This study also tried to find out if a 150 mg injection of DMPA was effective in preventing ovulation, the process by which the ovaries (the ovaries are part of the female reproductive system) release an egg for fertilization, for 12 weeks in women who are taking EFV and RIF. Another purpose of this study was to find out if it is safe to take RIF, EFV and DMPA at the same time.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection; Tuberculosis	Drug: Depot medroxyprogesterone acetate	Phase 2

Detailed Description

Globally, women comprise 52% of all people living with human immunodeficiency virus (HIV). Decisions about contraception in a population of women infected with both tuberculosis (TB) and HIV are of paramount importance. In the setting of the treatment of active TB, preventing pregnancy becomes even more important because it allows women to attain a level of health that will support healthy future pregnancies. Treatment options for TB may be limited in pregnancy because of concerns about teratogenicity. Millions of women around the world use depot medroxyprogesterone acetate (DMPA, trade name Depo-Provera) for prevention of pregnancy. DMPA is an intermediate-acting progesterone-only injectable contraceptive with a high efficacy rate. Unfortunately, DMPA's safety and effectiveness among women co-infected with TB and HIV is unknown since the interactions of TB treatment, combination ART (cART), and DMPA have not been well studied. The results of this study are likely to be applicable to women receiving RIF-containing TB treatment who are not being treated concurrently with EFV as well, given that addition of EFV to RIF is unlikely to increase induction of metabolizing enzymes significantly beyond the induction achieved with RIF alone.

The study population included premenopausal women, 18 to 46 years of age, who were co-infected with HIV and TB. To be eligible to enroll in the study, participants must have been on EFV 600 mg once daily plus two or more nucleoside reverse transcriptase inhibitors (NRTIs) for at least 28 days prior to study entry with no plans to change therapy for the 12 weeks of the study. Women must have been on the continuation phase of active TB treatment (with a minimum of 12 weeks remaining) taking RIF 8-12 mg/kg orally and INH 4-6 mg/kg orally on a 5-day or more per week schedule (or as directed by national guidelines for TB treatment). At study entry/week 0, DMPA 150 mg was administered intramuscularly as a single dose.

Study duration was 12 weeks. Visits occurred at weeks 0, 2, 4, 6, 8, 10, and 12. The key evaluations included physical examination, clinical assessments, hematology, chemistry, HIV RNA, pregnancy testing, plasma progesterone levels, and plasma DMPA concentration levels.

The sample size was 46 participants, of which 42 had to be evaluable. Participants who missed two successive visits prior to week 8 and those who did not complete the week 10 and week 12 clinic visits with available DMPA concentrations and progesterone levels were not evaluable and replaced in the sample size. The final number of participants enrolled was 62 participants, with only 42 evaluable.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Among Depot Medroxyprogesterone Acetate (DMPA), Rifampicin (RIF), and Efavirenz (EFV) in Women Co-infected With Human Immunodeficiency Virus (HIV) and Tuberculosis (TB)
• Actual Study Start Date: Nov 3, 2015
• Actual Primary Completion Date: Jun 15, 2017
• Actual Study Completion Date: Jun 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Depot medroxyprogesterone acetate At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).	Drug: Depot medroxyprogesterone acetate; Depot medroxyprogesterone acetate intramuscular injection; Other Names: DMPA

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Week 12 [Week 12]

   The percent of participants with plasma DMPA concentrations below 0.1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.

2. Percent of Participants With Progesterone Levels Above 1 ng/mL at Week 12 [Week 12]

   The percent of participants with plasma progesterone levels above 1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Ovulation generally occurs when the progesterone level is > 5 ng/mL. If there were participants with plasma progesterone levels > 1 ng/mL, then the percent of participants with plasma progesterone levels > 5 ng/mL would have been calculated by study week.

Secondary Outcome Measures

1. Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Weeks 2, 4, 6, 8, and 10 [Weeks 2, 4, 6, 8, and 10]

   The percents of participants with plasma DMPA concentrations below 0.1 ng/mL at weeks 2, 4, 6, 8, and 10 were calculated with exact Clopper-Pearson 95% confidence intervals. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.

2. Cumulative Percentage of Participants With DMPA < 0.1 ng/mL [Weeks 0, 2, 4, 6, 8, 10, and 12]

   The cumulative percentage of participants having a DMPA concentration less than 0.1 ng/mL at week 12 was calculated using a Kaplan-Meier estimator with an associated standard error. The confidence interval was calculated using a log-log transformation. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.

3. DMPA AUC [Weeks 0, 2, 4, 6, 8, 10, and 12]

   Describe the DMPA plasma area under the curve (AUC) between 0 and 12 weeks, where AUC(0-12wks) was calculated using non-compartmental methods.The Week 0 time point was drawn prior to DMPA injection.

4. DMPA Cmin [Weeks 0, 2, 4, 6, 8, 10, and 12]

   Describe the DMPA minimum observed concentration (Cmin) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.

5. DMPA Cmax [Weeks 0, 2, 4, 6, 8, 10, and 12]

   Describe the DMPA maximum observed concentration (Cmax) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.

6. DMPA CL/F [Weeks 0, 2, 4, 6, 8, 10, and 12]

   Describe the apparent DMPA clearance (CL/F) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.

7. Percent of Participants Who Experienced a Grade 3 or Higher Sign/Symptom or Laboratory Abnormality [Weeks 2, 4, 6, 8, 10, and 12]

   The percent of participants who experienced a grade 3 (severe) or higher sign/symptom or laboratory abnormality were calculated with an exact Clopper-Pearson 95% confidence interval. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS AE Grading Table (V1.0).

8. DMPA Half-life [Weeks 0, 2, 4, 6, 8, 10, and 12]

   Describe the terminal elimination half-life of DMPA (t½) between 0 and 12 weeks, where t½ was calculated using nonlinear mixed-effects (NLME) modelling. The Week 0 time point was drawn prior to DMPA injection.

9. Time at Which Participant-specific Estimated Elimination Slopes for DMPA Level Cross the Threshold of 0.1 ng/mL [Weeks 0, 2, 4, 6, 8, 10, and 12]

   Describe the time at which DMPA levels drop below the threshold of 0.1 ng/mL, based on participant-specific estimated elimination slopes from nonlinear mixed-effects (NLME) models. The Week 0 time point was drawn prior to DMPA injection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 46 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-1 infection.

• Current tuberculosis infection, confirmed or probable diagnosis.

• Currently stable on EFV-based cART for at least 28 days with no intention to change the regimen during the 12-week study period.

• Currently receiving RIF and Isoniazid (INH)-based TB therapy on at least 5 days per week schedule after completion of the intensive phase of TB treatment (minimum of 8 weeks of TB treatment) and expected to be on TB treatment for a minimum of 12 weeks after enrollment. [Does not exclude the use of ethambutol on study.]

• Premenopausal female with presumed normal ovarian function based on normal menstrual history and absence of previous ovarian dysfunction diagnosis.

• Last menstrual period (LMP) ≤35 days prior to study entry.

• Negative serum or urine-HCG pregnancy test within 30 days prior to study entry and negative pregnancy test at entry at any network-approved laboratory that operates in accordance with Good Clinical Practices and participates in appropriate external quality assurance programs.

• All participants 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. Women 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. Acceptable forms of contraceptives include:

• Condoms (male or female) with or without a spermicidal agent

• Diaphragm or cervical cap with spermicide

• Non-hormonal IUD

• Bilateral tubal ligation

• Male partner vasectomy

• Laboratory values within 30 days prior to study entry:

• Absolute neutrophil count ≥500 cells/mm^3

• Platelet count ≥50,000 platelets/mm^3

• Hemoglobin ≥8.0 g/dL

• Aspartate transaminase (AST) and alanine aminotransferase (ALT) <5 x upper limit of normal (ULN)

• Creatinine ≤1.5 x ULN

• Total bilirubin ≤2.0 x ULN

• Ability and willingness to provide written informed consent.

Exclusion Criteria:

• Receipt of DMPA or any other injectable contraceptive within 180 days prior to study entry.

• Receipt of other hormonal contraceptives within 30 days prior to study entry.

• Use of any drugs other than RIF and EFV known to: 1) induce CYP3A4 system within 30 days and to 2) inhibit the CYP3A4 system with one week prior to study entry. [Because ethambutol does not induce or inhibit the CYP3A4 system, its use is consistent with the language in the protocol.]

• ≤40 kg in weight.

• Bilateral oophorectomy.

• Less than 30 days postpartum at study entry.

• Hypersensitivity to DMPA, medroxyprogesterone acetate (MPA), or any of the other ingredients in DMPA.

• Any previous breast cancer diagnosis.

• Serious illness requiring systemic treatment and/or hospitalization within 21 days prior to study entry.

• Karnofsky performance score <70 within 14 days prior to study entry.

• Use of any immunosuppressant medication including systemic corticosteroids within 30 days prior to study entry.

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

• History of deep venous thrombosis or pulmonary emboli.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gaborone Prevention/Treatment Trials CRS (12701)	Gaborone		Botswana
2	Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460)	Kisumu		Kenya	40100
3	Durban Adult HIV CRS (11201)	Durban		South Africa	4013 SF
4	Univ. of Witwatersrand CRS (11101)	Johannesburg		South Africa
5	UZ-Parirenyatwa CRS (30313)	Harare		Zimbabwe

Sponsors and Collaborators

• AIDS Clinical Trials Group
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Rosie Mngqibisa, MBChB, MPH, Durban Adult HIV CRS
• Study Chair: Susan E. Cohn, MD, MPH, Northwestern University
• Study Chair: Jennifer Robinson, MD, MPH, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Aug 3, 2016
• Statistical Analysis Plan: Primary Statistical Analysis Plan - Apr 30, 2018
• Statistical Analysis Plan: PK Modeling Statistical Analysis Plan - Nov 28, 2018

More Information

Additional Information:

• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004; Clarification, August 2009
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Publications

None provided.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT02412436
• Other Study ID Numbers: ACTG A5338; UM1AI068636
• First Posted: Apr 9, 2015
• Last Update Posted: Jul 1, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tuberculosis; Medroxyprogesterone Acetate; Medroxyprogesterone

Study Results

Participant Flow

Recruitment Details	Study participants were recruited at five ACTG Clinical Research Sites in four countries (two sites from South Africa and one site from each of Botswana, Kenya, and Zimbabwe) between November 2015 and March 2017.
Pre-assignment Detail	Of the 85 women screened, 62 were deemed eligible and enrolled into this single-arm study.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Period Title: Overall Study
STARTED	62
COMPLETED	44
NOT COMPLETED	18

Baseline Characteristics

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Overall Participants	62
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	32
Age, Customized (Count of Participants)
20-29 years	24 38.7%
30-39 years	25 40.3%
40-49 years	13 21%
Sex: Female, Male (Count of Participants)
Female	62 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black African	62 100%
Region of Enrollment (Count of Participants)
Botswana	7 11.3%
Zimbabwe	8 12.9%
Kenya	12 19.4%
South Africa	35 56.5%
Body Mass Index (BMI) (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	20.8
HIV Antiretroviral Therapy (Count of Participants)
EFV + two NRTIs	62 100%
EFV + more than two NRTIs	0 0%
HIV RNA (Count of Participants)
< 400 copies/mL	52 83.9%
=> 400 copies/mL	9 14.5%
CD4+ Cell Count (cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm^3]	407
TB Treatment (Count of Participants)
RIF and INH	52 83.9%
RIF, INH, and ethambutol	10 16.1%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Week 12
Description	The percent of participants with plasma DMPA concentrations below 0.1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Number (95% Confidence Interval) [percentage of participants]	11.9 19.2%

2. Primary Outcome

Title	Percent of Participants With Progesterone Levels Above 1 ng/mL at Week 12
Description	The percent of participants with plasma progesterone levels above 1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Ovulation generally occurs when the progesterone level is > 5 ng/mL. If there were participants with plasma progesterone levels > 1 ng/mL, then the percent of participants with plasma progesterone levels > 5 ng/mL would have been calculated by study week.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Participants who did not have progesterone concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

3. Secondary Outcome

Title	Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Weeks 2, 4, 6, 8, and 10
Description	The percents of participants with plasma DMPA concentrations below 0.1 ng/mL at weeks 2, 4, 6, 8, and 10 were calculated with exact Clopper-Pearson 95% confidence intervals. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.
Time Frame	Weeks 2, 4, 6, 8, and 10

Outcome Measure Data

Analysis Population Description

Participants who did not have a DMPA concentration at the analysis week of interest were excluded from each analysis as appropriate. For example, participants missing a DMPA concentration at week 4 were excluded from the week 4 analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Week 2 DMPA < 0.1 ng/mL	0.0 0%
Week 4 DMPA < 0.1 ng/mL	0.0 0%
Week 6 DMPA < 0.1 ng/mL	0.0 0%
Week 8 DMPA < 0.1 ng/mL	0.0 0%
Week 10 DMPA < 0.1 ng/mL	2.4 3.9%

4. Secondary Outcome

Title	Cumulative Percentage of Participants With DMPA < 0.1 ng/mL
Description	The cumulative percentage of participants having a DMPA concentration less than 0.1 ng/mL at week 12 was calculated using a Kaplan-Meier estimator with an associated standard error. The confidence interval was calculated using a log-log transformation. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Number (95% Confidence Interval) [cumulative percentage of participants]	11.9 19.2%

5. Secondary Outcome

Title	DMPA AUC
Description	Describe the DMPA plasma area under the curve (AUC) between 0 and 12 weeks, where AUC(0-12wks) was calculated using non-compartmental methods.The Week 0 time point was drawn prior to DMPA injection.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Median (Inter-Quartile Range) [ng*week/mL]	7.63

6. Secondary Outcome

Title	DMPA Cmin
Description	Describe the DMPA minimum observed concentration (Cmin) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Median (Inter-Quartile Range) [ng/mL]	0.33

7. Secondary Outcome

Title	DMPA Cmax
Description	Describe the DMPA maximum observed concentration (Cmax) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Median (Inter-Quartile Range) [ng/mL]	1.04

8. Secondary Outcome

Title	DMPA CL/F
Description	Describe the apparent DMPA clearance (CL/F) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Median (Inter-Quartile Range) [L/week]	19681

9. Secondary Outcome

Title	Percent of Participants Who Experienced a Grade 3 or Higher Sign/Symptom or Laboratory Abnormality
Description	The percent of participants who experienced a grade 3 (severe) or higher sign/symptom or laboratory abnormality were calculated with an exact Clopper-Pearson 95% confidence interval. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS AE Grading Table (V1.0).
Time Frame	Weeks 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

All enrolled participants were included in the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	62
Number (95% Confidence Interval) [percentage of participants]	12.9 20.8%

10. Secondary Outcome

Title	DMPA Half-life
Description	Describe the terminal elimination half-life of DMPA (t½) between 0 and 12 weeks, where t½ was calculated using nonlinear mixed-effects (NLME) modelling. The Week 0 time point was drawn prior to DMPA injection.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Median (Inter-Quartile Range) [hours]	55

11. Secondary Outcome

Title	Time at Which Participant-specific Estimated Elimination Slopes for DMPA Level Cross the Threshold of 0.1 ng/mL
Description	Describe the time at which DMPA levels drop below the threshold of 0.1 ng/mL, based on participant-specific estimated elimination slopes from nonlinear mixed-effects (NLME) models. The Week 0 time point was drawn prior to DMPA injection.
Time Frame	Weeks 0, 2, 4, 6, 8, 10, and 12

Outcome Measure Data

Analysis Population Description

Participants who did not have DMPA concentrations at weeks 10 and 12 were excluded from the analysis.

Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Measure Participants	42
Median (Inter-Quartile Range) [days]	74.2

Adverse Events

Time Frame	Week 0 to either premature study discontinuation or Week 12
Adverse Event Reporting Description	The study protocol required reporting of all new diagnoses; all new signs and symptoms Grade 3 (severe) or higher; all new all Grade 3 or higher laboratory values; and all signs, symptoms, and laboratory values that led to a change in treatment, regardless of grade. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS AE Grading Table (V1.0) and reported per the EAE Manual (V2.0). All enrolled participants were included.
Arm/Group Title	Arm A: Depot Medroxyprogesterone Acetate
Arm/Group Description	At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
All Cause Mortality
	Arm A: Depot Medroxyprogesterone Acetate
	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)
Serious Adverse Events
	Arm A: Depot Medroxyprogesterone Acetate
	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)
Blood and lymphatic system disorders
Bicytopenia	1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Arm A: Depot Medroxyprogesterone Acetate
	Affected / at Risk (%)	# Events
Total	6/62 (9.7%)
Investigations
Neutrophil count decreased	6/62 (9.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.