Safety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV P... | NCT01705574

NCT01705574

ID	Type	Description	Link
2012-003708-11	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
E/C/F/TDF	Experimental	E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo	Drug: E/C/F/TDF Drug: ATV Placebo Drug: RTV Placebo Drug: FTC/TDF Placebo
ATV + RTV+ FTC/TDF	Active Comparator	ATV + RTV + FTC/TDF + E/C/F/TDF placebo	Drug: ATV Drug: RTV Drug: FTC/TDF Drug: E/C/F/TDF Placebo
Open-Label Extension Phase	Experimental	After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.	Drug: E/C/F/TDF Drug: ATV Drug: RTV Drug: FTC/TDF Drug: E/C/F/TAF

Name	Type	Description	Arm Group Labels	Other Names
E/C/F/TDF	Drug	150/150/200/300 mg FDC tablet administered orally with food once daily	E/C/F/TDF Open-Label Extension Phase

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the double-blind phase was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 48

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase		Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 for the STB Group as Determined by the US FDA-Defined Snapshot Algorithm	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Female (at birth), age ≥ 18 years
Ability to understand and sign a written informed consent form
Plasma HIV-1 RNA levels ≥ 500 copies/mL
No prior use of any approved or investigational antiretroviral drug for any length of time
Screening genotype report must show sensitivity to emtricitabine (FTC), tenofovir disoproxil fumarate (TDF) and atazanavir (ATV) boosted with ritonavir (RTV)
Normal ECG
Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
Hepatic transaminases ≤ 5 x upper limit of normal (ULN)
Total bilirubin ≤ 1.5 mg/dL
Adequate hematologic function
Serum amylase ≤ 5 x ULN
Women of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug
Women who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.

Key Exclusion Criteria:

A new AIDS defining condition diagnosed within the 30 days
Females receiving drug treatment for Hepatitis C, or females who are anticipated to receive treatment for Hepatitis C during the course of the study
Females experiencing decompensated cirrhosis
Females who are breastfeeding
Positive serum pregnancy test (female of childbearing potential)
Have an implanted defibrillator or pacemaker
Have an ECG pulse rate interval ≥ 220 msec
Current alcohol or substance use which may potentially interfere with the female's study compliance
History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
Participation in any other clinical trial without prior approval
Any other clinical condition or prior therapy that would make the female unsuitable for the study or unable to comply with the dosing requirements
Females receiving ongoing therapy with any disallowed medications, including drugs not to be used with elvitegravir, cobicistat, FTC, TDF, ATV, RTV; or females with any known allergies to the excipients of Stribild® tablets, Truvada® tablets, atazanavir capsules or ritonavir tablets

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California AIDS Clinical Trials Group		Los Angeles	California	90033	United States

References Module

Citations

PubMed Identifier	Type	Citation
27562742	Result	Squires K, Kityo C, Hodder S, Johnson M, Voronin E, Hagins D, Avihingsanon A, Koenig E, Jiang S, White K, Cheng A, Szwarcberg J, Cao H. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Lancet HIV. 2016 Sep;3(9):e410-e420. doi: 10.1016/S2352-3018(16)30016-9. Epub 2016 May 27.
	Result	Hodder S, Squires K, Gathe J, Kityo C, Supparatpinyo K, Moshkovich G, et al. Elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV)-boosted atazanavir (ATV) plus FTC/TDF in treatment-naive women with HIV-1 infection (WAVES study). Presented at Interscience Conference on Antimicrobial Agents and Chemotherapy and International Congress of Chemotherapy and Infection (ICAAC/ICC) 2015; September 17-21; San Diego, CA.
	Result	Squires K, Kityo C, Hodder S, Hagins D, Avihingsanon A, Plotnikova Y, et al. Elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV)-boosted atazanavir (ATV) plus FTC/TDF in treatment-naive women with HIV-1 infection (WAVES study). Poster no. MOLBPE08. Presented at 8th International Antiviral Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, 2015; 19-22 July, Vancouver, BC, Canada.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Double-Blind STB to Open-Label STB	Double-Blind (DB) Phase: Stribild® (STB; elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) 150/150/200/300 mg fixed-dose combination (FDC) + atazanavir (ATV) placebo + ritonavir (RTV) placebo + Truvada® (TVD; emtricitabine/tenofovir disoproxil fumarate; FTC/TDF) placebo orally once daily with food for 48 weeks Open-Label Extension (OLE) Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to receive open-label STB FDC orally once daily with food for 48 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Double-Blind STB to Open-Label STB	Double-Blind Phase: STB 150/150/200/300 mg FDC + ATV placebo + RTV placebo + TVD placebo orally once daily with food for 48 weeks Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to receive open-label STB FDC orally once daily with food for 48 weeks.
BG001	Double-Blind ATV+RTV+TVD to OL GEN or OL ATV+ RTV+TVD	Double-Blind Phase: ATV 300 mg + RTV 100 mg + TVD (200/300 mg) FDC + STB placebo orally once daily with food for 48 weeks Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and either receive open-label GEN 150/150/200/10 mg FDC or open-label ATV 300 mg + RTV 100 mg + TVD 200/300 mg FDC orally once daily with food for 48 weeks.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00036± 10.1 BG00136± 9.7 BG00236± 9.9

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000289 BG001286 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG0009 BG00117 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00020 BG00124 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Russia

Title	Measurements
	BG000101 BG00191 BG002

CD4 Cell Count

Mean

Standard Deviation

cells/µL

Title

Denominators

Categories

Title	Measurements
	BG000376± 199.6 BG001385± 210.2 BG002

HIV-1 RNA Category

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
≤ 100,000 copies/mL	BG000220 BG001214 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the double-blind phase was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Participants in the Intent-to-Treat (ITT) Analysis Set (randomized and received at least one dose of study drug) were analyzed.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	Double-Blind STB	Double-Blind Phase: STB 150/150/200/300 mg FDC + ATV placebo + RTV placebo + TVD placebo orally once daily with food for 48 weeks
OG001	Double-Blind ATV+RTV+TVD	Double-Blind Phase: ATV 300 mg boosted with RTV 100 mg + TVD (200/300 mg) FDC + E/C/F/TDF placebo once daily for 48 weeks

Units	Counts
Participants	OG000289 OG001286

Title

Denominators

Categories

Title	Measurements
	OG00087.2 OG00180.8

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Difference in proportions	6.5			2-Sided	95.2	0.4	12.6			Difference in percentages of virologic success and its 95.2% confidence interval (CI) were calculated based on baseline HIV-1 RNA and race stratum-adjusted Mantel-Haenszel (MH) proportion.		Non-Inferiority or Equivalence (legacy)	The null hypothesis was that the STB group was at least 12% worse than the ATV+RTV+TVD group with respect to the percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 (response rate as defined by the snapshot analysis algorithm). The alternative hypothesis was that the STB group was less than 12% worse than the ATV+RTV+TVD group.

Secondary

Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase

Participants in the ITT Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

cells/μL

Baseline; Week 48

ID	Title	Description
OG000	Double-Blind STB	Double-Blind Phase: STB 150/150/200/300 mg FDC + ATV placebo + RTV placebo + TVD placebo orally once daily with food for 48 weeks
OG001	Double-Blind ATV+RTV+TVD	Double-Blind Phase: ATV 300 mg + RTV 100 mg + TVD (200/300 mg) FDC + STB placebo orally once daily with food for 48 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 for the STB Group as Determined by the US FDA-Defined Snapshot Algorithm

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Participants in the ITT Analysis Set who received STB through 96 weeks were analyzed.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 96

ID	Title	Description
OG000	ALL STB	Double-Blind Phase: STB 150/150/200/300 mg FDC + ATV placebo + RTV placebo + TVD placebo orally once daily with food for 48 weeks Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had option to receive open-label STB FDC orally once daily with food for 48 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Receiving STB or ATV+RTV+TVD With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase

The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the open-label phase was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Participants in the OLE ITT Analysis Set were analyzed.

Posted

Number

Percentage of participants

Open-Label Extension Week 48

ID	Title	Description
OG000	Open-Label GEN	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and receive open-label GEN 150/150/200/10 mg FDC orally once daily with food for 48 weeks.
OG001	Open-Label ATV+RTV+TVD	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and receive open-label ATV 300 mg + RTV 100 mg + TVD 200/300 mg FDC orally once daily with food for 48 weeks.

Secondary

Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase

Participants in the OLE ITT Analysis Set with available on-treatment data were analyzed.

Posted

Mean

Standard Deviation

cells/uL

Baseline; Open-Label Extension Week 48

ID	Title	Description
OG000	Open-Label STB	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to receive open-label STB FDC orally once daily with food for 48 weeks.
OG001	Open-Label GEN	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and receive open-label GEN 150/150/200/10 mg FDC orally once daily with food for 48 weeks.
OG002	Open-Label ATV + RTV + TVD	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and receive open-label ATV 300 mg + RTV 100 mg + TVD 200/300 mg FDC orally once daily with food for 48 weeks.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-Blind: STB	Double-Blind Phase: STB 150/150/200/300 mg FDC + ATV placebo + RTV placebo + TVD placebo orally once daily with food for 48 weeks	25	289	176	289
EG001	Double-Blind: ATV+RTV+TVD	Double-Blind Phase: ATV 300 mg + RTV 100 mg + TVD (200/300 mg) FDC + STB placebo orally once daily with food for 48 weeks	29	286	194	286
EG002	DB STB to OL STB	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to receive open-label STB FDC orally once daily with food for 48 weeks.	13	246	118	246
EG003	DB ATV+RTV+TVD to OL GEN	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and receive open-label GEN 150/150/200/10 mg FDC orally once daily with food for 48 weeks.	12	159	68	159
EG004	DB ATV+RTV+TVD to OL ATV+RTV+TVD	Open-Label Extension Phase: After 48 weeks of blinded treatment participants continued on the blinded treatment for 12 weeks and returned for an unblinding visit at Week 60. Participants who were virologically suppressed at Week 48 during the double-blind phase had the option to be re-randomized and recieve open-label ATV 300 mg + RTV 100 mg + TVD (200/300 mg) FDC orally once daily with food for 48 weeks.	4	53	20	53

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0021 affected246 at risk EG0030 affected159 at risk EG0040 affected53 at risk
Haemorrhagic anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Cardiomegaly	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Coronary artery occlusion	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Chalazion	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0021 affected246 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Death	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Malaise	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Chronic hepatitis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Bone tuberculosis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Breast abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Catheter site infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Furuncle	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Malaria	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Ophthalmic herpes zoster	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Pelvic inflammatory disease	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Peritonitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected289 at risk EG0011 affected286 at risk EG0021 affected246 at risk EG003
Pulmonary tuberculosis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Subcutaneous abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Syphilis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Electrocardiogram T wave inversion	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0012 affected286 at risk EG0020 affected246 at risk EG003
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0002 affected289 at risk EG0012 affected286 at risk EG0021 affected246 at risk EG003
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Gestational hypertension	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Imminent abortion	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Ruptured ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Uterine hypertonus	Pregnancy, puerperium and perinatal conditions	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Conversion disorder	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Depression suicidal	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Major depression	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Stress	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Substance abuse	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0012 affected286 at risk EG0020 affected246 at risk EG003
Cervical dysplasia	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003
Neonatal respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0011 affected286 at risk EG0020 affected246 at risk EG003
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected289 at risk EG0010 affected286 at risk EG0021 affected246 at risk EG003
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG0010 affected286 at risk EG0020 affected246 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00011 affected289 at risk EG00114 affected286 at risk EG00218 affected246 at risk EG0034 affected159 at risk EG0040 affected53 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00017 affected289 at risk EG0019 affected286 at risk EG0021 affected246 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected289 at risk EG00119 affected286 at risk EG0026 affected246 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00013 affected289 at risk EG00115 affected286 at risk EG0024 affected246 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00043 affected289 at risk EG00141 affected286 at risk EG0026 affected246 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00028 affected289 at risk EG00117 affected286 at risk EG0023 affected246 at risk EG003
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG0008 affected289 at risk EG00115 affected286 at risk EG0022 affected246 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG00130 affected286 at risk EG0020 affected246 at risk EG003
Ocular icterus	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected289 at risk EG00134 affected286 at risk EG0020 affected246 at risk EG003
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00020 affected289 at risk EG00120 affected286 at risk EG00214 affected246 at risk EG003
Malaria	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00034 affected289 at risk EG00125 affected286 at risk EG00214 affected246 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00015 affected289 at risk EG00114 affected286 at risk EG0028 affected246 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00050 affected289 at risk EG00145 affected286 at risk EG00236 affected246 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00022 affected289 at risk EG00123 affected286 at risk EG00215 affected246 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00021 affected289 at risk EG00120 affected286 at risk EG00215 affected246 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected289 at risk EG00114 affected286 at risk EG0023 affected246 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected289 at risk EG00121 affected286 at risk EG0029 affected246 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00020 affected289 at risk EG00117 affected286 at risk EG00213 affected246 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00017 affected289 at risk EG00110 affected286 at risk EG0027 affected246 at risk EG003
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00049 affected289 at risk EG00144 affected286 at risk EG00227 affected246 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00021 affected289 at risk EG00120 affected286 at risk EG00212 affected246 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00020 affected289 at risk EG00118 affected286 at risk EG00212 affected246 at risk EG003

Certain Agreements

Ancestor Terms

ID	Term
D000069547	Cobicistat
D002219	Carbamates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000068698	Tenofovir
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D013844	Thiazoles
D013457	Sulfur Compounds
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D000068679	Emtricitabine
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D004338	Drug Combinations
D004364	Pharmaceutical Preparations
D011725	Pyridines
D009842	Oligopeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Term
D000163	Acquired Immunodeficiency Syndrome
D015658	HIV Infections

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D012897	Slow Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

ID	Term
D000069545	Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
D000069446	Atazanavir Sulfate
D019438	Ritonavir
D000069480	Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination