Trial Outcomes & Findings for HIV Treatment Reinitiation in Women Who Received Anti-HIV Drugs to Prevent Mother-to-Child Transmission of HIV (NCT NCT00442962)

NCT ID: NCT00442962

Last Updated: 2018-10-12

Results Overview

Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 54 participants
• Primary outcome timeframe: At Week 24
• Results posted on: 2018-10-12

Participant Flow

Study participants were recruited at 8 sites from 3 countries: 6 in the US, 1 in Brazil, 1 in Peru, between May 2007 to December 2009.

HIV-infected women, at least 16 years of age, whose only prior exposure to anti-retrovirals (ARVs) was for the purpose of prevention of mother-to-child transmission, who now qualify to start ARVs for their own health.

Participant milestones

Measure	EFV + FTC/TDF Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Overall Study STARTED	54
Overall Study Primary Outcome Evaluation	52
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	EFV + FTC/TDF Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Overall Study Pregnancy	1
Overall Study Lost to Follow-up	7

Baseline Characteristics

HIV Treatment Reinitiation in Women Who Received Anti-HIV Drugs to Prevent Mother-to-Child Transmission of HIV

Baseline characteristics by cohort

Measure	EFV + FTC/TDF n=54 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Age, Continuous	29 years STANDARD_DEVIATION 7 • n=5 Participants
Age, Customized Between 19 and 25 years	19 participants n=5 Participants
Age, Customized Between 26 and 30 years	16 participants n=5 Participants
Age, Customized Between 31 and 35 years	9 participants n=5 Participants
Age, Customized Between 36 and 40 years	6 participants n=5 Participants
Age, Customized Between 40 and 45 years	4 participants n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants
Region of Enrollment Brazil	22 participants n=5 Participants
Region of Enrollment Peru	20 participants n=5 Participants
CD4 count, Continuous	264 cells/mm^3 STANDARD_DEVIATION 104 • n=5 Participants
CD4 count, Categorical < 50 cells/mm^3	1 participants n=5 Participants
CD4 count, Categorical Between 50 and 99 cells/mm^3	0 participants n=5 Participants
CD4 count, Categorical Between 100 and 199 cells/mm^3	15 participants n=5 Participants
CD4 count, Categorical Between 200 and 299 cells/mm^3	18 participants n=5 Participants
CD4 count, Categorical Between 300 and 399 cells/mm^3	15 participants n=5 Participants
CD4 count, Categorical 400 or more cells/mm^3	5 participants n=5 Participants
Plasma HIV-1 RNA, Continuous	4.5 log10 copies/mL STANDARD_DEVIATION 0.6 • n=5 Participants
Plasma HIV-1 RNA, Categorical <= 400 copies/mL	0 participants n=5 Participants
Plasma HIV-1 RNA, Categorical Between 401 and 1000 copies/mL	1 participants n=5 Participants
Plasma HIV-1 RNA, Categorical Between 1001 and 10,000 copies/mL	8 participants n=5 Participants
Plasma HIV-1 RNA, Categorical Between 10,001 and 50,000 copies/mL	20 participants n=5 Participants
Plasma HIV-1 RNA, Categorical Between 50,001 and 75,000 copies/mL	11 participants n=5 Participants
Plasma HIV-1 RNA, Categorical Between 75,001 and 250,000 copies/mL	12 participants n=5 Participants
Plasma HIV-1 RNA, Categorical More than 250,000 copies/mL	2 participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 24

Population: Intention to treat (ignoring current study treatment status or history); closest measurement to week 24 used; missing measurements ignored. Exact binomial confidence interval calculated using method of Blyth-Still-Casella.

Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml

Outcome measures

Measure	EFV + FTC/TDF n=52 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Percentage of Participants With Early Virologic Response	80.8 percentage of participants Interval 67.8 to 90.4

SECONDARY outcome

Timeframe: Throughout study

Population: All enrolled participants who started study treatment (which in this case, matches the number of participants enrolled.)

Time from starting study treatment to first grade 3 or 4 sign/symptom or laboratory abnormality and at least one grade higher than baseline. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.

Outcome measures

Measure	EFV + FTC/TDF n=54 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Time to First Safety Event 5th percentile	4.1 weeks Interval 0.9 to 24.4
Time to First Safety Event 10th percentile	24.4 weeks Interval 0.9 to Not estimable as the upper limit for survival function at all weeks is above 90%
Time to First Safety Event 15th percentile	33.1 weeks Interval 4.1 to Not estimable as the upper limit for survival function at all weeks is above 85%

SECONDARY outcome

Timeframe: At Weeks 24

Population: ITT (ignoring current study treatment status and history); missing values ignored and closest value to week 24 used if multiple results available. 2 fewer results available compared to primary outcome b/c testing by ultrasensitive assay may have been retrospective.

Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml

Outcome measures

Measure	EFV + FTC/TDF n=50 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Percentage of Participants With Early Virologic Suppression	72.0 percentage of participants Interval 58.7 to 83.8

SECONDARY outcome

Timeframe: At Week 48

Population: Participants with plasma HIV-1 RNA viral load result available from week 48 study visit.

Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml

Outcome measures

Measure	EFV + FTC/TDF n=46 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Percentage of Participants With Late Virologic Response	80.43 percentage Interval 67.1 to 89.7

SECONDARY outcome

Timeframe: Throughout study

Population: All enrolled participants included.

Time from enrollment to scheduled week of first plasma HIV-1 RNA viral load fewer than 400 copies/mL.

Outcome measures

Measure	EFV + FTC/TDF n=54 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Time to Initial Virologic Response 50th percentile	2 weeks Interval 2.0 to 4.0
Time to Initial Virologic Response 75th percentile	8 weeks Interval 4.0 to 16.0
Time to Initial Virologic Response 95th percentile	24 weeks Interval 16.0 to Not estimable as the upper limit for survival function at all weeks is above 95%

SECONDARY outcome

Timeframe: Throughout study

Population: All participants enrolled are included.

Virologic failure defined as two consecutive measurements of plasma HIV-1 RNA at least 400 copies/mL at or after the week 16 study visit. Time measured from enrollment.

Outcome measures

Measure	EFV + FTC/TDF n=54 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Time to Initial Virological Failure 5th percentile	16 weeks Interval 16.0 to 16.0
Time to Initial Virological Failure 10th percentile	16 weeks Interval 16.0 to 36.0
Time to Initial Virological Failure 15th percentile	24 weeks Interval 16.0 to Not estimable as the upper limit for survival function at all weeks is above 85%

SECONDARY outcome

Timeframe: Throughout study

Population: All enrolled participants included.

Outcome measures

Measure	EFV + FTC/TDF n=54 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm) 10th percentile	16 weeks Interval 0.0 to 24.0
Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm) 15th percentile	24 weeks Interval 0.0 to 36.0
Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm) 20th percentile	24 weeks Interval 4.0 to Not estimable as the upper limit for survival function at all weeks is above 80%

SECONDARY outcome

Timeframe: At weeks 0(baseline), 4, 8, 16, 24

Population: Intent to treat (study treatment status and history ignored); missing measurements ignored.

Changes in CD4+ lymphocyte counts between study visit weeks 4, 8 16 and 24 and baseline.

Outcome measures

Measure	EFV + FTC/TDF n=51 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Early Changes in CD4 Count From Baseline Change from baseline to week 4	105 cells/mm^3 Standard Deviation 108
Early Changes in CD4 Count From Baseline Change from baseline to week 8	118 cells/mm^3 Standard Deviation 87
Early Changes in CD4 Count From Baseline Change from baseline to week 16	138 cells/mm^3 Standard Deviation 112
Early Changes in CD4 Count From Baseline Change from baseline to week 24	147 cells/mm^3 Standard Deviation 147

SECONDARY outcome

Timeframe: At Week 48

Population: Participants with ultra-sensitive (detectable to 50 copies/mL) plasma HIV-1 RNA result available from week 48 visit.

Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml

Outcome measures

Measure	EFV + FTC/TDF n=44 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Percentage of Participants With Late Virologic Suppression	70.5 percentage Interval 55.8 to 82.1

SECONDARY outcome

Timeframe: Throughout study

Population: All enrolled participants who started study treatment.

Time from starting study treatment to first dose/drug modification.

Outcome measures

Measure	EFV + FTC/TDF n=54 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Time to First Dose Modification 10th percentile	1.9 weeks Interval 0.4 to 25.7
Time to First Dose Modification 15th percentile	24.9 weeks Interval 1.1 to 39.1
Time to First Dose Modification 20th percentile	25.7 weeks Interval 1.9 to Not estimable as the upper limit for survival function at all weeks is above 80%

SECONDARY outcome

Timeframe: At week 48

Population: Participants with a CD4+ lymphocyte cell count result from the week 48 study visit.

Change in CD4+ lymphocyte counts between week 48 study visit and baseline.

Outcome measures

Measure	EFV + FTC/TDF n=46 Participants Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Late Change in CD4 Count From Baseline	194 cells/mm^3 Standard Deviation 185

Adverse Events

EFV+FTC/TDF

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	EFV+FTC/TDF n=54 participants at risk Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Psychiatric disorders Suicide attempt	1.9% 1/54

Other adverse events

Measure	EFV+FTC/TDF n=54 participants at risk Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate for 48 weeks
Gastrointestinal disorders Diarrhoea	7.4% 4/54
Gastrointestinal disorders Nausea	11.1% 6/54
Gastrointestinal disorders Vomiting	9.3% 5/54
General disorders Pyrexia	9.3% 5/54
Immune system disorders Drug hypersensitivity	5.6% 3/54
Infections and infestations Sinusitis bacterial	7.4% 4/54
Infections and infestations Urinary tract infection	9.3% 5/54
Infections and infestations Vulvovaginal candidiasis	11.1% 6/54
Investigations Alanine aminotransferase increased	9.3% 5/54
Investigations Aspartate aminotransferase increased	13.0% 7/54
Investigations Blood alkaline phosphatase increased	7.4% 4/54
Investigations Blood cholesterol	7.4% 4/54
Investigations Haemoglobin decreased	11.1% 6/54
Investigations Low density lipoprotein abnormal	7.4% 4/54
Investigations Neutrophil count decreased	11.1% 6/54
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 3/54
Nervous system disorders Dizziness	11.1% 6/54
Nervous system disorders Headache	13.0% 7/54
Nervous system disorders Somnolence	9.3% 5/54
Psychiatric disorders Abnormal dreams	13.0% 7/54
Psychiatric disorders Insomnia	7.4% 4/54
Renal and urinary disorders Dysuria	7.4% 4/54
Reproductive system and breast disorders Vaginal discharge	11.1% 6/54
Reproductive system and breast disorders Vulvovaginal pruritus	5.6% 3/54
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.4% 4/54
Skin and subcutaneous tissue disorders Pruritus	14.8% 8/54
Skin and subcutaneous tissue disorders Pruritus generalised	5.6% 3/54

Additional Information

ACTG ClinicalTrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: ACTGCT.Gov@s-3.com

Results disclosure agreements

• Principal investigator is a sponsor employee In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER