Trial Outcomes & Findings for Sofosbuvir-Containing Regimens Without Interferon For Treatment of Acute Hepatitis C Virus (HCV) Infection (NCT NCT02128217)

Last Updated: 2018-04-27

Results Overview

SVR12 was defined as HCV RNA undetectable less than the lower limit of quantification, Target Not Detected (\<LLOQ TND) of the assay at 12 weeks after date of last dose of study treatment. For both Cohort 1 and Cohort 2, the 12 week measurement used for determining SVR12 was the measurement obtained closest to 84 days (i.e. 12\*7 days), within the window 79 to 112 days inclusive. If a participant did not have an HCV RNA measurement within this window, then the participant was considered as having detectable HCV RNA at 12 weeks unless the preceding and subsequent HCV RNA measurements were both undetectable (\<LLOQ TND). A two-sided 90% confidence interval was calculated for this percentage using the Blyth-Still-Casella method.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

44 participants

Primary outcome timeframe

At 12 weeks after date of last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Results posted on

2018-04-27

Participant Flow

Participants were enrolled at 12 different study sites in the United States. For Cohort 1, the first participant enrolled on 30 May 2014; the last participant enrolled on 7 October 2014. For Cohort 2, the first participant enrolled on 31 August 2015; the last participant enrolled on 27 September 2015.

Participant milestones

Participant milestones
Measure	Cohort 1: SOF+Weight-based RBV for 12 Wks Follow-up occurred through to 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.
Overall Study STARTED	17	27
Overall Study COMPLETED	17	26
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: SOF+Weight-based RBV for 12 Wks Follow-up occurred through to 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

One participant in Cohort 1 did not have HIV RNA results obtained at baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through to 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin(RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Total n=44 Participants Total of all reporting groups
Age, Continuous	45 Years n=17 Participants	46 Years n=27 Participants	45.5 Years n=44 Participants
Age, Customized Age · 20-29 years	3 Participants n=17 Participants	1 Participants n=27 Participants	4 Participants n=44 Participants
Age, Customized Age · 30-39 years	1 Participants n=17 Participants	8 Participants n=27 Participants	9 Participants n=44 Participants
Age, Customized Age · 40-49 years	10 Participants n=17 Participants	10 Participants n=27 Participants	20 Participants n=44 Participants
Age, Customized Age · 50-59 years	2 Participants n=17 Participants	6 Participants n=27 Participants	8 Participants n=44 Participants
Age, Customized Age · 60-69 years	1 Participants n=17 Participants	1 Participants n=27 Participants	2 Participants n=44 Participants
Age, Customized Age · 70+ years	0 Participants n=17 Participants	1 Participants n=27 Participants	1 Participants n=44 Participants
Sex: Female, Male Female	0 Participants n=17 Participants	0 Participants n=27 Participants	0 Participants n=44 Participants
Sex: Female, Male Male	17 Participants n=17 Participants	27 Participants n=27 Participants	44 Participants n=44 Participants
Race/Ethnicity, Customized Race/Ethnicity · White Non-Hispanic	6 Participants n=17 Participants	11 Participants n=27 Participants	17 Participants n=44 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black Non-Hispanic	0 Participants n=17 Participants	5 Participants n=27 Participants	5 Participants n=44 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic (Regardless of Race)	11 Participants n=17 Participants	9 Participants n=27 Participants	20 Participants n=44 Participants
Race/Ethnicity, Customized Race/Ethnicity · Asian, Pacific Islander	0 Participants n=17 Participants	2 Participants n=27 Participants	2 Participants n=44 Participants
Region of Enrollment United States	17 Participants n=17 Participants	27 Participants n=27 Participants	44 Participants n=44 Participants
Intravenous Drug History Never	13 Participants n=17 Participants	22 Participants n=27 Participants	35 Participants n=44 Participants
Intravenous Drug History Currently	0 Participants n=17 Participants	1 Participants n=27 Participants	1 Participants n=44 Participants
Intravenous Drug History Previously	4 Participants n=17 Participants	4 Participants n=27 Participants	8 Participants n=44 Participants
Weight Less than 75 kg	7 Participants n=17 Participants	12 Participants n=27 Participants	19 Participants n=44 Participants
Weight Greater than or equal to 75 kg	10 Participants n=17 Participants	15 Participants n=27 Participants	25 Participants n=44 Participants
Type of Acute HCV Infection New Infection	17 Participants n=17 Participants	22 Participants n=27 Participants	39 Participants n=44 Participants
Type of Acute HCV Infection Reinfection	0 Participants n=17 Participants	5 Participants n=27 Participants	5 Participants n=44 Participants
HCV Genotype 1a	11 Participants n=17 Participants	23 Participants n=27 Participants	34 Participants n=44 Participants
HCV Genotype 1b	2 Participants n=17 Participants	3 Participants n=27 Participants	5 Participants n=44 Participants
HCV Genotype 1 (subtype unknown)	2 Participants n=17 Participants	0 Participants n=27 Participants	2 Participants n=44 Participants
HCV Genotype 2b	1 Participants n=17 Participants	0 Participants n=27 Participants	1 Participants n=44 Participants
HCV Genotype 4	0 Participants n=17 Participants	1 Participants n=27 Participants	1 Participants n=44 Participants
HCV Genotype Indeterminate	1 Participants n=17 Participants	0 Participants n=27 Participants	1 Participants n=44 Participants
IL28B Genotype CC	4 Participants n=17 Participants	16 Participants n=27 Participants	20 Participants n=44 Participants
IL28B Genotype CT	10 Participants n=17 Participants	7 Participants n=27 Participants	17 Participants n=44 Participants
IL28B Genotype TT	3 Participants n=17 Participants	4 Participants n=27 Participants	7 Participants n=44 Participants
HCV RNA	2280000 IU/mL n=17 Participants	1490000 IU/mL n=27 Participants	1500000 IU/mL n=44 Participants
HCV RNA Levels < 6 million IU/mL	15 Participants n=17 Participants	21 Participants n=27 Participants	36 Participants n=44 Participants
HCV RNA Levels >= 6 million IU/mL	2 Participants n=17 Participants	6 Participants n=27 Participants	8 Participants n=44 Participants
HIV RNA <50 copies/mL	15 Participants n=16 Participants • One participant in Cohort 1 did not have HIV RNA results obtained at baseline.	27 Participants n=27 Participants • One participant in Cohort 1 did not have HIV RNA results obtained at baseline.	42 Participants n=43 Participants • One participant in Cohort 1 did not have HIV RNA results obtained at baseline.
HIV RNA >= 50 copies/mL	1 Participants n=16 Participants • One participant in Cohort 1 did not have HIV RNA results obtained at baseline.	0 Participants n=27 Participants • One participant in Cohort 1 did not have HIV RNA results obtained at baseline.	1 Participants n=43 Participants • One participant in Cohort 1 did not have HIV RNA results obtained at baseline.
Received HIV ARVs Prior to Study Entry Yes	16 Participants n=17 Participants	27 Participants n=27 Participants	43 Participants n=44 Participants
Received HIV ARVs Prior to Study Entry No	1 Participants n=17 Participants	0 Participants n=27 Participants	1 Participants n=44 Participants
History of Sexually Transmitted Infections Reported History of STI Diagnosis	8 Participants n=17 Participants	11 Participants n=27 Participants	19 Participants n=44 Participants
History of Sexually Transmitted Infections No History of STI Diagnosis	9 Participants n=17 Participants	16 Participants n=27 Participants	25 Participants n=44 Participants

PRIMARY outcome

Timeframe: At 12 weeks after date of last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who enrolled and started at least one dose of study treatment

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Percentage of Participants With Sustained Virologic Response 12 (SVR12)	100.0 Percentage of participants Interval 89.9 to 100.0	58.8 Percentage of participants Interval 36.4 to 77.5

PRIMARY outcome

Timeframe: From initiation of study treatment to 28 days after last dose of study treatment. The duration for study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who enrolled and started first dose of study treatment.

Any adverse event occurring after initiation of study treatment through to 28 days after the date of last dose of study treatment was included (except that an event that was ongoing at the same grade from before start of study treatment was excluded). Adverse events consisted of Grade ≥ 2 primary diagnosis, primary sign/symptoms, and primary laboratory abnormality. It also included any serious adverse event according to ICH criteria and any treatment-limiting AE (ie, an AE reported as the reason for permanent discontinuation of study treatment). A two-sided 90% confidence interval was calculated for the percentage using the Blyth-Still-Casella method.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Percentage of Participants With an Occurrence of a Grade ≥ 2 Adverse Event, Serious AE According to ICH Criteria, or Treatment-limiting AE.	33.3 Percentage of participants Interval 20.4 to 50.0	47.1 Percentage of participants Interval 27.7 to 68.9

SECONDARY outcome

Timeframe: 1, 2, 4, 8 and, for the 12-week regimen, 12 weeks after starting study treatment.

Population: Participants who successfully enrolled and started first dose of treatment.

HCV RNA undetectable was defined as an HCV RNA measurement \<LLOQ, TND. If there was no measurement at a scheduled time, then the participant was considered as having detectable HCV RNA at that time, unless both the preceding and succeeding measurements were undetectable. A two-sided 90% confidence interval was calculated for each proportion using the Blyth-Still-Casella method.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Percentage of Participants With HCV RNA Undetectable During Study Treatment On-treatment Week 1	18.5 Percentage of participants Interval 9.3 to 34.7	11.8 Percentage of participants Interval 3.2 to 31.1
Percentage of Participants With HCV RNA Undetectable During Study Treatment On Treatment Week 2	44.4 Percentage of participants Interval 29.1 to 61.8	29.4 Percentage of participants Interval 14.0 to 50.0
Percentage of Participants With HCV RNA Undetectable During Study Treatment On-treatment Week 4	81.5 Percentage of participants Interval 65.3 to 90.7	70.6 Percentage of participants Interval 50.0 to 86.6
Percentage of Participants With HCV RNA Undetectable During Study Treatment On-treatment Week 8	92.6 Percentage of participants Interval 79.6 to 98.0	100.0 Percentage of participants Interval 86.0 to 100.0
Percentage of Participants With HCV RNA Undetectable During Study Treatment On-treatment Week 12	NA Percentage of participants On treatment week 12 visits did not apply to Cohort 2 because Cohort 2 was assigned only 8 weeks of treatment.	100.0 Percentage of participants Interval 86.0 to 100.0

SECONDARY outcome

Timeframe: 2, 4, 8 and 24 weeks after last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who successfully enrolled and started first dose of treatment. Note that one participant in Cohort 2 was lost to follow-up prior to week 24 and is imputed as not having SVR24 at week 24. This participant, however, had HCV RNA \< LLOQ, TND at all moments from week 4 of study treatment.

HCV RNA undetectable is defined as an HCV RNA measurement \<LLOQ, TND. If there was no measurement at a scheduled time, then the participant was considered as having detectable HCV RNA at that time, unless both the preceding and succeeding measurements were undetectable. This outcome measure was referred to as SVR2, SVR4, SVR8 and SVR24 where SVR means sustained virologic response. A two-sided 90% confidence interval was calculated for the percentage using the Blyth-Still-Casella method.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Percentage of Participants With HCV RNA Undetectable After End of Study Treatment SVR2	100.0 Percentage of participants Interval 89.9 to 100.0	64.7 Percentage of participants Interval 43.2 to 82.5
Percentage of Participants With HCV RNA Undetectable After End of Study Treatment SVR4	96.3 Percentage of participants Interval 84.3 to 99.6	58.8 Percentage of participants Interval 36.4 to 77.5
Percentage of Participants With HCV RNA Undetectable After End of Study Treatment SVR8	96.3 Percentage of participants Interval 84.3 to 99.6	58.8 Percentage of participants Interval 36.4 to 77.5
Percentage of Participants With HCV RNA Undetectable After End of Study Treatment SVR24	96.3 Percentage of participants Interval 84.3 to 99.6	64.7 Percentage of participants Interval 43.2 to 82.5

SECONDARY outcome

Timeframe: From end of study treatment through to 24 weeks after end of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who successfully enrolled and started first dose of treatment.

HCV virologic relapse was defined as HCV RNA undetectable at end-of-treatment but HCV RNA quantifiable during follow-up with subsequent confirmation as quantifiable.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Number of Participants Who Had HCV Virologic Relapse	0 Participants	7 Participants

SECONDARY outcome

Timeframe: At time of HCV virologic failure; any time from start of study treatment to 24 weeks after end of study treatment. Duration of study treatment for Cohort 1 and 2 were 12 and 8 weeks, respectively.

Population: Participants who observed an HCV virologic failure after successfully enrolling for first dose of treatment.

Percentage of participants who developed SOF- or LDV-associated resistance mutation found within HCV Virologic Failure participants. HCV virologic failure was defined as HCV RNA undetectable at end-of-treatment but HCV RNA quantifiable during follow-up with subsequent confirmation as quantifiable.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=7 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Percentage of HCV Virologic Failure Participants That Developed SOF- or LDV-Associated Resistance Mutations	—	0.00 Percentage of participants

SECONDARY outcome

Timeframe: Any time from start of treatment to 28 days after date of last dose of study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who successfully enrolled and received first dose of treatment.

The adverse events considered were Grade 2 or higher adverse events (primary diagnosis, primary sign and symptom, or a primary lab), SAE according to ICH criteria, or treatment-limiting adverse events. Participants may experience more than one type of adverse event.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Count and Percentage of Participants With an Adverse Event by Type. Primary Diagnosis	2 Participants	0 Participants
Count and Percentage of Participants With an Adverse Event by Type. Primary Sign/Symptom	4 Participants	5 Participants
Count and Percentage of Participants With an Adverse Event by Type. Primary Lab	6 Participants	5 Participants
Count and Percentage of Participants With an Adverse Event by Type. Serious Adverse Event	1 Participants	0 Participants
Count and Percentage of Participants With an Adverse Event by Type. Treatment-Limiting Adverse Event	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4 and 12 weeks after start of study treatment for Cohort 1. 4 and 8 weeks after start of study treatment for the 8-week regimen used in Cohort 2)

Population: Participants who enrolled successfully, received HIV ARV regimen at entry and started first dose of treatment

Because all except one participant had HIV-1 RNA \< 50 copies/mL, participants were categorized according to whether or not their HIV-1 RNA was \<5 copies/mL at each follow-up evaluation.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Count of Participants With HIV-1 RNA <50 Copies/mL On-treatment Week 4 · ≥50 copies/mL	0 Participants	0 Participants
Count of Participants With HIV-1 RNA <50 Copies/mL On-treatment Week 4 · <50 copies/mL	27 Participants	17 Participants
Count of Participants With HIV-1 RNA <50 Copies/mL On-treatment Week 8 · ≥50 copies/mL	0 Participants	0 Participants
Count of Participants With HIV-1 RNA <50 Copies/mL On-treatment Week 8 · <50 copies/mL	23 Participants	0 Participants
Count of Participants With HIV-1 RNA <50 Copies/mL On-treatment Week 12 · ≥50 copies/mL	0 Participants	0 Participants
Count of Participants With HIV-1 RNA <50 Copies/mL On-treatment Week 12 · <50 copies/mL	0 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline to 12 weeks after end of study treatment. Duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who successfully enrolled and recieved first dose of treatment.

The change in CD4+ cell count from baseline to 12 weeks after the end of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=24 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=16 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Change in CD4+ Cell Count	61 cells/mm^3 Standard Deviation 125	11 cells/mm^3 Standard Deviation 111

SECONDARY outcome

Timeframe: 1, 2, 4, 8 and 12 weeks after starting study treatment.

Population: Participants in Cohort 1 who successfully enrolled and received first dose of SOF+weight-based RBV.

Count and percentage of participants who reported having taken all doses of SOF. This outcome measure was evaluated in Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Self-reported Adherence to SOF Week 1	—	17 Participants
Self-reported Adherence to SOF Week 2	—	16 Participants
Self-reported Adherence to SOF Week 4	—	16 Participants
Self-reported Adherence to SOF Week 8	—	16 Participants
Self-reported Adherence to SOF Week 12	—	15 Participants

SECONDARY outcome

Timeframe: 12 weeks after starting study treatment.

Population: Participants in Cohort 1 who successfully enrolled and received first dose of SOF+weight-based RBV.

The count and percentage of participants who had a pill count consistent with 100% of SOF doses taken. This outcome measure was evaluated in Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Adherence as Measured by SOF Pill Count Pill count not available	—	12 Participants
Adherence as Measured by SOF Pill Count Pill count consistent with 100% of doses taken	—	4 Participants
Adherence as Measured by SOF Pill Count Pill count indicates <100% of doses taken	—	1 Participants

SECONDARY outcome

Timeframe: 1, 2, 4, 8 and 12 weeks after starting study treatment.

Population: Participants in Cohort 1 who successfully enrolled and received first dose of SOF+weight-based RBV.

Count and percentage of participants who reported having taken all doses of RBV. This outcome measure was evaluated in Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Self-reported Adherence to RBV Week 1	—	16 Participants
Self-reported Adherence to RBV Week 2	—	15 Participants
Self-reported Adherence to RBV Week 4	—	15 Participants
Self-reported Adherence to RBV Week 8	—	16 Participants
Self-reported Adherence to RBV Week 12	—	15 Participants

SECONDARY outcome

Timeframe: 12 weeks after starting study treatment.

Population: Participants in Cohort 1 who successfully enrolled and received first dose of SOF + weight-based RBV.

The count and percentage of participants who had a pill count consistent with 100% of RBV doses taken. This outcome measure was evaluated in Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Adherence as Measured by RBV Pill Count Pill count not available	—	12 Participants
Adherence as Measured by RBV Pill Count Pill count consistent with 100% of doses taken	—	1 Participants
Adherence as Measured by RBV Pill Count Pill count indicates <100% of doses taken	—	4 Participants

SECONDARY outcome

Timeframe: 1, 2, 4, and 8 weeks after starting study treatment.

Population: Participants in Cohort 2 who successfully enrolled and received first dose of LDV/SOF.

Count and percentage of participants who reported having taken all doses of LDV/SOF. This outcome measure was evaluated in Cohort 2 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Self-reported Adherence to LDV/SOF Week 1	25 Participants	—
Self-reported Adherence to LDV/SOF Week 2	25 Participants	—
Self-reported Adherence to LDV/SOF Week 4	27 Participants	—
Self-reported Adherence to LDV/SOF Week 8	18 Participants	—

SECONDARY outcome

Timeframe: 8 weeks after starting study treatment.

Population: Participants in Cohort 2 who successfully enrolled and received first dose of LDV/SOF.

The count and percentage of participants who had a pill count consistent with 100% of LDV/SOF doses taken.. This outcome measure was evaluated in Cohort 2 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=27 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Adherence as Measured by LDV/SOF Pill Count Pill count not available	7 Participants	—
Adherence as Measured by LDV/SOF Pill Count Pill count consistent with 100% of doses taken	17 Participants	—
Adherence as Measured by LDV/SOF Pill Count Pill count indicates <100% of doses taken	3 Participants	—

SECONDARY outcome

Timeframe: 4, 8, and 12 weeks after starting study treatment.

Population: Participants in Cohort 1 who successfully enrolled and received first dose of SOF + weight-based RBV.

Ribavirin concentration in plasma. This outcome was evaluated in Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Ribavirin Concentration in Plasma Week 4	—	1803 ng/mL Geometric Coefficient of Variation 45.6
Ribavirin Concentration in Plasma week 8	—	2122 ng/mL Geometric Coefficient of Variation 30.0
Ribavirin Concentration in Plasma Week 12	—	2013 ng/mL Geometric Coefficient of Variation 36.4

SECONDARY outcome

Timeframe: Baseline (before HCV study treatment), EOT (end of trial dosing), 12 weeks after end of HCV study treatment. The duration of HCV study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively.

Population: Participants who started first dose of study treatment and also took tenofovir disoporxil fumarate (TDF) for treatment of HIV infection.

Cellular concentration of tenofovir diphosphate (TFV-DP) from dried blood spot samples.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=22 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=15 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Cellular Concentration of Tenofovir Diphosphate (TFV-DP) Baseline	1516 fmol/punch Geometric Coefficient of Variation 36.2	1687 fmol/punch Geometric Coefficient of Variation 30.7
Cellular Concentration of Tenofovir Diphosphate (TFV-DP) End of treatment	26846 fmol/punch Geometric Coefficient of Variation 49.3	6607 fmol/punch Geometric Coefficient of Variation 73.8
Cellular Concentration of Tenofovir Diphosphate (TFV-DP) 12 Weeks after end of HCV study treatment	1644 fmol/punch Geometric Coefficient of Variation 54.6	2100 fmol/punch Geometric Coefficient of Variation 36.4

SECONDARY outcome

Timeframe: Baseline (before SOF + RBV dosing), EOT (end of study treatment), 12 weeks after end of HCV study treatment.

Population: Participants in Cohort 1 who successfully enrolled and received first dose of SOF + weight-based RBV and who were also taking tenofovir disoproxil fumarate (TDF) for treatment of HIV infection.

Concentration of tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs). This outcome is measured in Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=15 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Concentration of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) Baseline	—	79 fmol/10^6 cells Geometric Coefficient of Variation 47.9
Concentration of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) End of treatment	—	149 fmol/10^6 cells Geometric Coefficient of Variation 91.3
Concentration of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) 12 Weeks after end of HCV study treatment	—	81 fmol/10^6 cells Geometric Coefficient of Variation 54.4

SECONDARY outcome

Population: Participants who started first dose of study treatment and also took tenofovir (TFV) for treatment of HIV infection.

Concentration of tenofovir (TFV) in plasma among participants who took TFV for treatment of HIV infection.

Outcome measures

Outcome measures
Measure	Cohort 2: LDV/SOF for 8 Wks n=22 Participants Follow-up occurred through to 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir (LDV/SOF): Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.	Cohort 1: SOF+Weight-based RBV for 12 Wks n=15 Participants Follow-up occurred through 24 weeks after the end of treatment. Sofosbuvir (SOF): Participants received one 400 mg tablet of sofosbuvir orally every morning with food. Ribavirin (RBV): Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management.
Concentration of Tenofovir (TFV) in Plasma Baseline	87 ng/mL Geometric Coefficient of Variation 97.6	98 ng/mL Geometric Coefficient of Variation 62.6
Concentration of Tenofovir (TFV) in Plasma End of treatment	155 ng/mL Geometric Coefficient of Variation 112.1	96 ng/mL Geometric Coefficient of Variation 57.2
Concentration of Tenofovir (TFV) in Plasma 12 Weeks after end of HCV study treatment	76 ng/mL Geometric Coefficient of Variation 66.2	94 ng/mL Geometric Coefficient of Variation 75.7

Adverse Events

Cohort 1: SOF+Weight-based RBV for 12 Wks

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Cohort 2: LDV/SOF for 8 Wks

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: SOF+Weight-based RBV for 12 Wks n=17 participants at risk Follow-up occurred 24 weeks after the end of treatment. Ribavirin: Participants received weight-based RBV orally, 2 times a day, every morning and every evening, with food. Weight under 75 kg, 600 mg (3 tablets) morning and 400 mg (2 tablets) evening. Weight over 75 kg, 600 mg (3 tablets) morning and 600 mg (3 tablets) evening. The dose of RBV was based on subject's weight at entry. Changes in weight after entry did not require a change in dose. Doses were only changed for toxicity management. Sofosbuvir: Participants received one 400 mg tablet of sofosbuvir orally every morning with food.	Cohort 2: LDV/SOF for 8 Wks n=27 participants at risk Follow-up occurred 24 weeks after the end of treatment. Ledipasvir/Sofosbuvir: Participants received one daily fixed-dose combination tablet orally every morning of 90 mg of LDV and 400 mg of SOF.
Cardiac disorders Coronary artery disease	0.00% 0/17 • From study entry to 24 weeks after completing study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively. The study protocol required reporting of all new diagnoses, signs/symptoms and laboratory events of \>=Grade 2, SAEs, and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade. All signs/symptoms and laboratory results that were observed or performed as part of establishing a diagnosis were requested regardless of grade. The DAIDS AE Grading Table (V2.0) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment are included.	3.7% 1/27 • From study entry to 24 weeks after completing study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively. The study protocol required reporting of all new diagnoses, signs/symptoms and laboratory events of \>=Grade 2, SAEs, and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade. All signs/symptoms and laboratory results that were observed or performed as part of establishing a diagnosis were requested regardless of grade. The DAIDS AE Grading Table (V2.0) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment are included.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/17 • From study entry to 24 weeks after completing study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively. The study protocol required reporting of all new diagnoses, signs/symptoms and laboratory events of \>=Grade 2, SAEs, and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade. All signs/symptoms and laboratory results that were observed or performed as part of establishing a diagnosis were requested regardless of grade. The DAIDS AE Grading Table (V2.0) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment are included.	3.7% 1/27 • From study entry to 24 weeks after completing study treatment. The duration of study treatment for Cohort 1 and Cohort 2 were 12 and 8 weeks, respectively. The study protocol required reporting of all new diagnoses, signs/symptoms and laboratory events of \>=Grade 2, SAEs, and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade. All signs/symptoms and laboratory results that were observed or performed as part of establishing a diagnosis were requested regardless of grade. The DAIDS AE Grading Table (V2.0) and EAE Manual (V2.0) were used. All eligible participants who initiated study treatment are included.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials 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.
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