Hepatic Safety of Raltegravir Versus Efavirenz as HIV Therapy for Patients With HIV and HCV Coinfection

• Sponsor: University of Hawaii (Other)
• Overall Status: Completed
• CT.gov ID: NCT01147107
• Collaborator: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (Other), Viet Tiep General Hospital, Hai Phong, Vietnam (Other), Oxford University Clinical Research Unit, Vietnam (Other)
• Enrollment: 80
• Locations: 2
• Arms: 2
• Actual Duration (Months): 88
• Patients Per Site: 40
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The main objective is to evaluate the hepatic safety of raltegravir when compared to efavirenz, both in combination with tenofovir and emtricitabine as first-line HIV treatment in patients with HIV and hepatitis C coinfection.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic; HIV Infection	Drug: Raltegravir; Drug: Efavirenz	Phase 4

Detailed Description

The trial will recruit 80 treatment-naive HIV-infected patients with chronic hepatitis C coinfection from two HIV treatment centers in Vietnam. Patients will be randomized to receive either raltegravir or efavirenz, both in combination of tenofovir and emtricitabine, as first-line HIV therapy over a period of 72 weeks. The primary endpoint is the rate of alanine aminotransferase (ALT) elevation during the 72 week study period. Secondary endpoints include rates of virological suppression, CD4 count change, numbers of AIDS events and death, rates of fasting glucose and cholesterol measures, neurocognitive function and levels of immune activation. Patients will be followed monthly for the first 3 months and every 3 months thereafter. At the end of the trial period, patients will be transferred to the National HIV treatment program for continuation of HIV therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hepatic Safety of Raltegravir-based and Efavirenz-based Antiretroviral Regimens in Antiretroviral-Naïve HIV-infected Subjects Co-Infected With Hepatitis C
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Raltegravir based therapy Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily	Drug: Raltegravir; Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily; Other Names: Isentress
Active Comparator: Efavirenz based therapy Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily	Drug: Efavirenz; Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily; Other Names: Sustiva

Outcome Measures

Primary Outcome Measures

1. Rates of Grade 2 and Higher Alanine Aminotransferase (ALT) Elevations [over week 72]

   To estimate the rates of grade 2*and higher ALT elevations in the two regimens.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV infected patients, age >18 years, meet Vietnam guideline to begin ART (CD4 count < 350 cells/mm3 and/or WHO stage III or IV disease)

• Hepatitis C infection as documented by positive HCV antibodies and a detectable serum HCV RNA level

• AST and ALT ≤ 2 x ULN (≤ 80 U/L)

• Estimated creatinine clearance ≥ 60 mL/min

Exclusion Criteria:

• Any prior ART

• Positive Hepatitis B surface antigen

• Clinical evidence of de-compensated cirrhosis (ascites, encephalopathy, esophageal bleeding)

• Requirement for acute therapy for other AIDS-defining illness within 14 days prior to study entry

• Currently on rifampicin therapy

• In the first trimester of pregnancy, intent to become pregnant, or breast feeding during the study period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Viet Tiep General Hospital	Hai Phong		Vietnam
2	Hospital for Tropical Diseases	Ho Chi Minh City		Vietnam

Sponsors and Collaborators

• University of Hawaii
• Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
• Viet Tiep General Hospital, Hai Phong, Vietnam
• Oxford University Clinical Research Unit, Vietnam

Investigators

• Principal Investigator: Van Vinh Chau Nguyen, MD, PhD, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
• Principal Investigator: Cecilia M Shikuma, M.D., University of Hawaii - Hawaii Center for AIDS (HICFA)
• Study Director: Thuy Le, M.D., University of Hawaii, Oxford University Clinical Research Unit

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Hawaii
• ClinicalTrials.gov Identifier: NCT01147107
• Other Study ID Numbers: VHARP 001
• First Posted: Jun 22, 2010
• Last Update Posted: Aug 13, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by University of Hawaii: HIV/HCV co-infection; Antiretroviral therapy
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Efavirenz; Raltegravir Potassium

Study Results

Participant Flow

Arm/Group Title	Raltegravir Based Therapy	Efavirenz Based Therapy
Arm/Group Description	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily Raltegravir: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily Efavirenz: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
Period Title: Overall Study
STARTED	39	41
COMPLETED	33	40
NOT COMPLETED	6	1

Baseline Characteristics

Arm/Group Title	Raltegravir Based Therapy	Efavirenz Based Therapy	Total
Arm/Group Description	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily Raltegravir: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily Efavirenz: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily	Total of all reporting groups
Overall Participants	38	41	79
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	32	33	32
Sex: Female, Male (Count of Participants)
Female	6 15.8%	4 9.8%	10 12.7%
Male	32 84.2%	37 90.2%	69 87.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	38 100%	41 100%	79 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Vietnam	38 100%	41 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	Rates of Grade 2 and Higher Alanine Aminotransferase (ALT) Elevations
Description	To estimate the rates of grade 2*and higher ALT elevations in the two regimens.
Time Frame	over week 72

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Raltegravir Based Therapy	Efavirenz Based Therapy
Arm/Group Description	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily Raltegravir: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily Efavirenz: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
Measure Participants	38	41
Count of Participants [Participants]	24 63.2%	30 73.2%

Adverse Events

Time Frame	72 weeks
Arm/Group Title	Raltegravir Based Therapy		Efavirenz Based Therapy
Arm/Group Description	Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily Raltegravir: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily		Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily Efavirenz: Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
All Cause Mortality
	Raltegravir Based Therapy		Efavirenz Based Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/38 (5.3%)		3/41 (7.3%)
Serious Adverse Events
	Raltegravir Based Therapy		Efavirenz Based Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/38 (21.1%)		8/41 (19.5%)
Blood and lymphatic system disorders
Lymphadenitis	1/38 (2.6%)	1	0/41 (0%)	0
Gastrointestinal disorders
Infectious Diarrhea	0/38 (0%)	0	1/41 (2.4%)	1
Appendicitis	0/38 (0%)	0	1/41 (2.4%)	1
General disorders
Suicide	0/38 (0%)	0	1/41 (2.4%)	1
Hepatobiliary disorders
Hepatic Encephalopathy	1/38 (2.6%)	1	0/41 (0%)	0
Infections and infestations
Septic Shock	1/38 (2.6%)	1	0/41 (0%)	0
Injury, poisoning and procedural complications
Car Accident	1/38 (2.6%)	1	0/41 (0%)	0
Nervous system disorders
CNS Syndrome Unclear Etiology	0/38 (0%)	0	1/41 (2.4%)	1
PML	0/38 (0%)	0	1/41 (2.4%)	1
Renal and urinary disorders
Pyelonephritis	1/38 (2.6%)	1	0/41 (0%)	0
Respiratory, thoracic and mediastinal disorders
Tuberculosis	1/38 (2.6%)	1	3/41 (7.3%)	3
PCP Pneumonia	1/38 (2.6%)	1	0/41 (0%)	0
Bacterial Pneumonia	1/38 (2.6%)	1	0/41 (0%)	0
Other (Not Including Serious) Adverse Events
	Raltegravir Based Therapy		Efavirenz Based Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/38 (55.3%)		29/41 (70.7%)
Hepatobiliary disorders
ALT Elevation	21/38 (55.3%)		29/41 (70.7%)

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.