Preventing Sexual Transmission of HIV With Anti-HIV Drugs

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00074581
• Collaborator: HIV Prevention Trials Network (Other)
• Enrollment: 3,526
• Locations: 17
• Arms: 2
• Duration (Months): 122.9
• Patients Per Site: 207.4
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study will determine whether anti-HIV drugs can prevent the sexual transmission of HIV among couples in which one partner is HIV infected and the other is not.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Atazanavir; Drug: Didanosine; Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Lamivudine; Drug: Lopinavir/Ritonavir; Drug: Nevirapine; Drug: Stavudine; Drug: Tenofovir disoproxil fumarate; Drug: Zidovudine/Lamivudine	Phase 3

Detailed Description

Initiation of antiretroviral therapy (ART) in the HIV infected population has been shown to dramatically reduce the morbidity and mortality of HIV infection through sustained reduction in HIV viral replication. However, such therapy does not cure HIV infection or prevent the spread of the virus. ART may, however, make HIV infected people less contagious by lowering plasma HIV-1 RNA levels, compared with people not on ART. This study seeks to determine whether initiating ART in ART-naive, HIV infected people can prevent the sexual transmission of HIV among HIV-discordant couples, as well as to demonstrate whether quality of life changes with the initiation of ART. Both opposite and same sex couples will be recruited at study sites in Brazil, India, Malawi, Thailand, the United States, and Zimbabwe for this study.

Participating couples will be enrolled for approximately 78 months (6.5 years). Couples will be randomly assigned to one of two arms. HIV infected partners in Arm 1 will begin ART in addition to receiving HIV primary care. HIV infected partners in Arm 2 will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. All couples will receive HIV counseling and have their urine and blood collected at screening and enrollment, and at selected monthly, quarterly, and yearly intervals. They will be asked to periodically report information about their adherence to the ART regimen.

Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3526 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Randomized Trial to Evaluate the Effectiveness of Antiretroviral Therapy Plus HIV Primary Care Versus HIV Primary Care Alone to Prevent the Sexual Transmission of HIV-1 in Serodiscordant Couples
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Participants will begin ART in addition to receiving HIV primary care	Drug: Atazanavir; 300 mg taken orally once daily; Other Names: Reyataz ; Drug: Didanosine; 400 mg taken orally once daily; Other Names: Videx ; Drug: Efavirenz; 600 mg taken orally once daily; Other Names: Sustiva ; Drug: Emtricitabine/Tenofovir disoproxil fumarate; 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily; Other Names: Truvada ; Drug: Lamivudine; 300 mg taken orally once daily; Other Names: Epivir 3TC ; Drug: Lopinavir/Ritonavir; 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily; Other Names: Kaletra ; Drug: Nevirapine; 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily; Other Names: Viramune NVP ; Drug: Stavudine; Dosage depends on weight; Other Names: Zerit d4T ; Drug: Tenofovir disoproxil fumarate; 300 mg taken orally once daily; Other Names: Viread TDF ; Drug: Zidovudine/Lamivudine; 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily; Other Names: Combivir
Experimental: 2 Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.	Drug: Atazanavir; 300 mg taken orally once daily; Other Names: Reyataz ; Drug: Didanosine; 400 mg taken orally once daily; Other Names: Videx ; Drug: Efavirenz; 600 mg taken orally once daily; Other Names: Sustiva ; Drug: Emtricitabine/Tenofovir disoproxil fumarate; 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily; Other Names: Truvada ; Drug: Lamivudine; 300 mg taken orally once daily; Other Names: Epivir 3TC ; Drug: Lopinavir/Ritonavir; 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily; Other Names: Kaletra ; Drug: Nevirapine; 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily; Other Names: Viramune NVP ; Drug: Stavudine; Dosage depends on weight; Other Names: Zerit d4T ; Drug: Tenofovir disoproxil fumarate; 300 mg taken orally once daily; Other Names: Viread TDF ; Drug: Zidovudine/Lamivudine; 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily; Other Names: Combivir

Outcome Measures

Primary Outcome Measures

1. Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms [Throughout study]

   incident HIV infections occurring in the partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases are assessed, by arm. Only acquisition from the index partner were included in the primary analysis, therefore, each endpoint was required to be confirmed (by genotyping) such that the viral envelop sequence in the index case matched that of the partner.

2. All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms [Throughout study]

   All Incident HIV infections occurring in the partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases are assessed, by arm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria for HIV Infected Partner:

• Positive HIV test within 60 days of study entry

• CD4 count between 350 and 550 cells/mm3 within 30 days of study entry

• If pregnant or breastfeeding, willing to be randomized to either arm of the study

Inclusion Criteria for HIV Uninfected Partner:

• Negative HIV test within 14 days of study entry

Inclusion Criteria for Both Partners:

• Plans to maintain sexual relationship with partner

• Reports having sex (vaginal or anal) with partner at least three times in the last 3 months

• Willing to disclose HIV test results to partner

• Plans to stay in the area and does not have a job or other obligations that may require long absences during the duration of the study

Exclusion Criteria for HIV Infected Partner:

• Current or previous use of any ART. Participants who previously took a short-term course of ART for prevention of mother-to-child transmission of HIV are not excluded.

• Documented or suspected acute hepatitis within 30 days of study entry, if the infected partner's starting regimen in the study contains nevirapine or atazanavir

• Current or previous AIDS-defining illness or opportunistic infection

• Documented or suspected acute hepatitis within 30 days prior to study entry

• Acute therapy of serious medical illnesses within 14 days prior to study entry

• Radiation therapy or systemic chemotherapy within 45 days prior to study entry

• Immunomodulatory or investigational therapy within 30 days prior to study entry

• Active drug or alcohol dependence that, in the opinion of the investigator, would interfere with the study

• Vomiting or inability to swallow medications

• Require certain medications

• Allergy or sensitivity to any of the study drugs

Exclusion Criteria for Both Partners:

• History of injection drug use within 5 years of study entry

• Previous and/or current participation in an HIV vaccine study

• Currently detained in jail or for treatment of a psychiatric or physical illness

• Any condition that, in the opinion of the study staff, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

• Certain abnormal laboratory values

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fenway Community Health Ctr. CRS	Boston	Massachusetts	United States	02115
2	Gaborone CRS	Gaborone		Botswana
3	Hospital Geral de Nova Iguaçu CRS (HGNI CRS)	Nova Iguacu	Rio De Janeiro	Brazil	26030-380
4	Hospital Nossa Senhora da Conceicao CRS	Port Alegre	Rio Grande Do Sul	Brazil	91350 200
5	HSE-Hospital dos Servidores do Estado CRS	Rio de Janeiro		Brazil	20221-903
6	Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS	Rio de Janeiro		Brazil	21040-360
7	NARI Clinic at Gadikhana Dr. Kotnis Municipal Dispensary CRS	Pune	Maharashtra	India	411002
8	NARI Clinic at NIV CRS	Pune	Maharashtra	India	411011
9	NARI Pune CRS	Pune	Maharashtra	India	411026
10	Chennai Antiviral Research and Treatment (CART) CRS	Chennai	Tamil Nadu	India	600113
11	Kisumu Crs	Kisumu	Nyanza	Kenya	40100
12	Blantyre CRS	Blantyre		Malawi
13	Malawi CRS	Lilongwe		Malawi
14	Soweto HPTN CRS	Johannesburg	Gauteng	South Africa	2001
15	Wits Helen Joseph Hospital CRS (Wits HJH CRS)	Johannesburg	Gauteng	South Africa	2092
16	CMU HIV Prevention CRS	Chiang Mai		Thailand	50202
17	Parirenyatwa CRS	Harare		Zimbabwe

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• HIV Prevention Trials Network

Investigators

• Study Chair: Myron S. Cohen, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chan DJ. Factors affecting sexual transmission of HIV-1: current evidence and implications for prevention. Curr HIV Res. 2005 Jul;3(3):223-41. Review.
• Chan DJ. Fatal attraction: sex, sexually transmitted infections and HIV-1. Int J STD AIDS. 2006 Oct;17(10):643-51. Review.
• Davis CW, Doms RW. HIV transmission: closing all the doors. J Exp Med. 2004 Apr 19;199(8):1037-40. Epub 2004 Apr 12. Review.
• Gupta K, Klasse PJ. How do viral and host factors modulate the sexual transmission of HIV? Can transmission be blocked? PLoS Med. 2006 Feb;3(2):e79. Epub 2006 Feb 28. Review.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00074581
• Other Study ID Numbers: HPTN 052; 10068
• First Posted: Dec 17, 2003
• Last Update Posted: Nov 5, 2021
• Last Verified: Nov 1, 2016

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): HIV Infections; HIV Seronegativity
• Additional relevant MeSH terms: HIV Infections; Ritonavir; Lopinavir; Atazanavir Sulfate; Tenofovir; Lamivudine; Zidovudine; Emtricitabine; Nevirapine; Didanosine; Stavudine; Efavirenz

Study Results

Participant Flow

Arm/Group Title	Early-ART	Delayed-ART
Arm/Group Description	Participants will begin ART in addition to receiving HIV primary care Atazanavir: 300 mg taken orally once daily Didanosine: 400 mg taken orally once daily Efavirenz: 600 mg taken orally once daily Emtricitabine/Tenofovir disoproxil fumarate: 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Lamivudine: 300 mg taken orally once daily Lopinavir/Ritonavir: 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily Nevirapine: 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily Stavudine: Dosage depends on weight Tenofovir disoproxil fumarate: 300 mg taken orally once daily Zidovudine/Lamivudine: 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily Note: Sites could also use locally supplied, FDA-approved drugs if they could be purchased with nonstudy funds. For participants with virologic failure, specified second-line treatment regimens were provided.	Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. (Same drug regimen as that described in the early-ART arm) Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.
Period Title: Overall Study
STARTED	1789	1767
COMPLETED	1545	1541
NOT COMPLETED	244	226

Baseline Characteristics

Arm/Group Title	Early-ART	Delayed-ART	Total
Arm/Group Description	Participants will begin ART in addition to receiving HIV primary care Atazanavir: 300 mg taken orally once daily Didanosine: 400 mg taken orally once daily Efavirenz: 600 mg taken orally once daily Emtricitabine/Tenofovir disoproxil fumarate: 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Lamivudine: 300 mg taken orally once daily Lopinavir/Ritonavir: 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily Nevirapine: 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily Stavudine: Dosage depends on weight Tenofovir disoproxil fumarate: 300 mg taken orally once daily Zidovudine/Lamivudine: 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily Note: Sites could also use locally supplied, FDA-approved drugs if they could be purchased with nonstudy funds. For participants with virologic failure, specified second-line treatment regimens were provided.	Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. (Same drug regimen as that described in the early-ART arm) Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.	Total of all reporting groups
Overall Participants	1789	1767	3556
Age, Customized (participants) [Number]
18-25 yr	300 16.8%	335 19%	635 17.9%
26-40 yr	1101 61.5%	1079 61.1%	2180 61.3%
>40 yr	388 21.7%	353 20%	741 20.8%
Sex: Female, Male (Count of Participants)
Female	877 49%	860 48.7%	1737 48.8%
Male	912 51%	907 51.3%	1819 51.2%
Region (participants) [Number]
North or South America	293 16.4%	279 15.8%	572 16.1%
Asia	535 29.9%	528 29.9%	1063 29.9%
Africa	961 53.7%	960 54.3%	1921 54%

Outcome Measures

1. Primary Outcome

Title	Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms
Description	incident HIV infections occurring in the partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases are assessed, by arm. Only acquisition from the index partner were included in the primary analysis, therefore, each endpoint was required to be confirmed (by genotyping) such that the viral envelop sequence in the index case matched that of the partner.
Time Frame	Throughout study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Early-ART	Delayed-ART
Arm/Group Description	Participants will begin ART in addition to receiving HIV primary care Atazanavir: 300 mg taken orally once daily Didanosine: 400 mg taken orally once daily Efavirenz: 600 mg taken orally once daily Emtricitabine/Tenofovir disoproxil fumarate: 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Lamivudine: 300 mg taken orally once daily Lopinavir/Ritonavir: 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily Nevirapine: 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily Stavudine: Dosage depends on weight Tenofovir disoproxil fumarate: 300 mg taken orally once daily Zidovudine/Lamivudine: 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily Note: Sites could also use locally supplied, FDA-approved drugs if they could be purchased with nonstudy funds. For participants with virologic failure, specified second-line treatment regimens were provided.	Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. (Same drug regimen as that described in the early-ART arm) Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.
Measure Participants	903	890
Measure Person Years	4325	4185
Number (95% Confidence Interval) [event rate per 100 person-yr]	0.07	1.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Early-ART, Delayed-ART
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.02 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio estimate presented (0.07) is a comparison of the early-ART arm (numerator) to the delayed-ART arm (denominator), thus indicating a 93% lower risk of infection among all linked partner infections, during the entire study.

2. Primary Outcome

Title	All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms
Description	All Incident HIV infections occurring in the partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases are assessed, by arm.
Time Frame	Throughout study

Outcome Measure Data

Analysis Population Description

Population includes all partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases, by arm.

Arm/Group Title	Early-ART	Delayed-ART
Arm/Group Description	Participants will begin ART in addition to receiving HIV primary care Atazanavir: 300 mg taken orally once daily Didanosine: 400 mg taken orally once daily Efavirenz: 600 mg taken orally once daily Emtricitabine/Tenofovir disoproxil fumarate: 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Lamivudine: 300 mg taken orally once daily Lopinavir/Ritonavir: 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily Nevirapine: 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily Stavudine: Dosage depends on weight Tenofovir disoproxil fumarate: 300 mg taken orally once daily Zidovudine/Lamivudine: 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily Note: Sites could also use locally supplied, FDA-approved drugs if they could be purchased with nonstudy funds. For participants with virologic failure, specified second-line treatment regimens were provided.	Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. (Same drug regimen as that described in the early-ART arm) Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.
Measure Participants	903	890
Number (95% Confidence Interval) [event rate per 100 person-yr]	0.44	1.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Early-ART, Delayed-ART
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.31
	Confidence Interval	(2-Sided) 95%; 0.19 to 0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio estimate presented (0.31) is a comparison of the early-ART arm (numerator) to the delayed-ART arm (denominator), thus indicating a 69% lower risk of infection among all partner infections, during the entire study.

Adverse Events

Adverse Event Reporting Description	Only index participants were monitored for adverse events since they (and not partners) were receiving treatment drugs.
Arm/Group Title	Early-ART		Delayed-ART
Arm/Group Description	Participants will begin ART in addition to receiving HIV primary care Atazanavir: 300 mg taken orally once daily Didanosine: 400 mg taken orally once daily Efavirenz: 600 mg taken orally once daily Emtricitabine/Tenofovir disoproxil fumarate: 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Lamivudine: 300 mg taken orally once daily Lopinavir/Ritonavir: 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily Nevirapine: 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily Stavudine: Dosage depends on weight Tenofovir disoproxil fumarate: 300 mg taken orally once daily Zidovudine/Lamivudine: 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily Note: Sites could also use locally supplied, FDA-approved drugs if they could be purchased with nonstudy funds. For participants with virologic failure, specified second-line treatment regimens were provided.		Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. (Same drug regimen as that described in the early-ART arm) Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.
All Cause Mortality
	Early-ART		Delayed-ART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Early-ART		Delayed-ART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	526/886 (59.4%)		522/877 (59.5%)
Blood and lymphatic system disorders
Anaemia	15/886 (1.7%)		19/877 (2.2%)
Anaemia of pregnancy	1/886 (0.1%)		1/877 (0.1%)
Febrile neutropenia	0/886 (0%)		1/877 (0.1%)
Haemolytic anaemia	1/886 (0.1%)		0/877 (0%)
Iron deficiency anaemia	1/886 (0.1%)		0/877 (0%)
Leukopenia	1/886 (0.1%)		3/877 (0.3%)
Lymphadenitis	0/886 (0%)		1/877 (0.1%)
Lymphadenopathy	0/886 (0%)		1/877 (0.1%)
Neutropenia	62/886 (7%)		66/877 (7.5%)
Pancytopenia	1/886 (0.1%)		1/877 (0.1%)
Thrombocytopenia	6/886 (0.7%)		6/877 (0.7%)
Cardiac disorders
Acute coronary syndrome	1/886 (0.1%)		0/877 (0%)
Cardiac arrest	1/886 (0.1%)		0/877 (0%)
Cardiac failure	1/886 (0.1%)		0/877 (0%)
Cor pulmonale	0/886 (0%)		1/877 (0.1%)
Left ventricular failure	1/886 (0.1%)		0/877 (0%)
Myocardial infarction	0/886 (0%)		2/877 (0.2%)
Palpitations	0/886 (0%)		1/877 (0.1%)
Congenital, familial and genetic disorders
Congenital anomaly in offspring	0/886 (0%)		1/877 (0.1%)
Hydrocele	0/886 (0%)		1/877 (0.1%)
Ear and labyrinth disorders
Vertigo	2/886 (0.2%)		1/877 (0.1%)
Vertigo positional	1/886 (0.1%)		0/877 (0%)
Eye disorders
Retinal artery occlusion	0/886 (0%)		1/877 (0.1%)
Ulcerative keratitis	0/886 (0%)		1/877 (0.1%)
Gastrointestinal disorders
Abdominal hernia	0/886 (0%)		1/877 (0.1%)
Abdominal pain	1/886 (0.1%)		6/877 (0.7%)
Acute abdomen	1/886 (0.1%)		0/877 (0%)
Anal ulcer	1/886 (0.1%)		0/877 (0%)
Diarrhoea	9/886 (1%)		7/877 (0.8%)
Diarrhoea haemorrhagic	6/886 (0.7%)		9/877 (1%)
Dyspepsia	1/886 (0.1%)		1/877 (0.1%)
Enteritis	1/886 (0.1%)		0/877 (0%)
Food poisoning	1/886 (0.1%)		1/877 (0.1%)
Gastritis	0/886 (0%)		2/877 (0.2%)
Gastrointestinal haemorrhage	1/886 (0.1%)		0/877 (0%)
Haemorrhoids	0/886 (0%)		2/877 (0.2%)
Inguinal hernia	0/886 (0%)		1/877 (0.1%)
Intestinal obstruction	2/886 (0.2%)		0/877 (0%)
Mouth ulceration	1/886 (0.1%)		0/877 (0%)
Nausea	2/886 (0.2%)		4/877 (0.5%)
Pancreatitis	0/886 (0%)		2/877 (0.2%)
Peptic ulcer	2/886 (0.2%)		1/877 (0.1%)
Vomiting	3/886 (0.3%)		4/877 (0.5%)
General disorders
Asthenia	1/886 (0.1%)		0/877 (0%)
Chest pain	0/886 (0%)		1/877 (0.1%)
Death	7/886 (0.8%)		5/877 (0.6%)
Fatigue	3/886 (0.3%)		2/877 (0.2%)
Hyperthermia	1/886 (0.1%)		0/877 (0%)
Influenza like illness	0/886 (0%)		1/877 (0.1%)
Injection site pain	1/886 (0.1%)		0/877 (0%)
Multi-organ failure	0/886 (0%)		1/877 (0.1%)
Peripheral swelling	0/886 (0%)		1/877 (0.1%)
Polyp	1/886 (0.1%)		0/877 (0%)
Pyrexia	4/886 (0.5%)		5/877 (0.6%)
Hepatobiliary disorders
Cholelithiasis	1/886 (0.1%)		0/877 (0%)
Cirrhosis alcoholic	0/886 (0%)		1/877 (0.1%)
Drug-induced liver injury	1/886 (0.1%)		0/877 (0%)
Hepatic cirrhosis	1/886 (0.1%)		1/877 (0.1%)
Hepatic failure	0/886 (0%)		1/877 (0.1%)
Hepatitis	4/886 (0.5%)		1/877 (0.1%)
Hepatitis acute	1/886 (0.1%)		1/877 (0.1%)
Hepatitis alcoholic	1/886 (0.1%)		2/877 (0.2%)
Hepatotoxicity	6/886 (0.7%)		4/877 (0.5%)
Hyperbilirubinaemia	37/886 (4.2%)		14/877 (1.6%)
Liver disorder	1/886 (0.1%)		5/877 (0.6%)
Immune system disorders
Anaphylactic reaction	0/886 (0%)		1/877 (0.1%)
Drug hypersensitivity	0/886 (0%)		2/877 (0.2%)
Hypersensitivity	0/886 (0%)		3/877 (0.3%)
Infections and infestations
Abortion infected	0/886 (0%)		1/877 (0.1%)
Abscess	0/886 (0%)		1/877 (0.1%)
Abscess bacterial	2/886 (0.2%)		0/877 (0%)
Acute sinusitis	0/886 (0%)		1/877 (0.1%)
Appendicitis	1/886 (0.1%)		4/877 (0.5%)
Appendicitis perforated	1/886 (0.1%)		0/877 (0%)
Bacterial pyelonephritis	2/886 (0.2%)		0/877 (0%)
Bacterial sepsis	1/886 (0.1%)		0/877 (0%)
Bronchitis	0/886 (0%)		1/877 (0.1%)
Cellulitis	3/886 (0.3%)		4/877 (0.5%)
Cerebral malaria	1/886 (0.1%)		1/877 (0.1%)
Dengue fever	1/886 (0.1%)		4/877 (0.5%)
Diarrhoea infectious	1/886 (0.1%)		0/877 (0%)
Disseminated tuberculosis	1/886 (0.1%)		2/877 (0.2%)
Dysentery	1/886 (0.1%)		4/877 (0.5%)
Enteritis infectious	0/886 (0%)		1/877 (0.1%)
Erysipelas	1/886 (0.1%)		0/877 (0%)
Extrapulmonary tuberculosis	1/886 (0.1%)		6/877 (0.7%)
Furuncle	0/886 (0%)		2/877 (0.2%)
Gastroenteritis	12/886 (1.4%)		19/877 (2.2%)
Gastrointestinal infection	0/886 (0%)		2/877 (0.2%)
H1N1 influenza	1/886 (0.1%)		0/877 (0%)
Herpes zoster	2/886 (0.2%)		5/877 (0.6%)
Herpes zoster oticus	0/886 (0%)		1/877 (0.1%)
Influenza	2/886 (0.2%)		2/877 (0.2%)
Joint abscess	0/886 (0%)		1/877 (0.1%)
Leptospirosis	4/886 (0.5%)		2/877 (0.2%)
Liver abscess	0/886 (0%)		1/877 (0.1%)
Lower respiratory tract infection	1/886 (0.1%)		0/877 (0%)
Lower respiratory tract infection bacterial	0/886 (0%)		1/877 (0.1%)
Lymph node tuberculosis	0/886 (0%)		2/877 (0.2%)
Malaria	23/886 (2.6%)		20/877 (2.3%)
Measles	1/886 (0.1%)		0/877 (0%)
Meningitis	4/886 (0.5%)		2/877 (0.2%)
Meningitis bacterial	1/886 (0.1%)		1/877 (0.1%)
Meningitis cryptococcal	1/886 (0.1%)		0/877 (0%)
Meningitis tuberculous	0/886 (0%)		2/877 (0.2%)
Meningococcal sepsis	1/886 (0.1%)		0/877 (0%)
Meningoencephalitis herpetic	0/886 (0%)		1/877 (0.1%)
Muscle abscess	0/886 (0%)		1/877 (0.1%)
Nasal abscess	0/886 (0%)		1/877 (0.1%)
Nasopharyngitis	1/886 (0.1%)		1/877 (0.1%)
Osteomyelitis chronic	1/886 (0.1%)		0/877 (0%)
Pelvic abscess	1/886 (0.1%)		0/877 (0%)
Pelvic inflammatory disease	8/886 (0.9%)		6/877 (0.7%)
Pharyngitis	0/886 (0%)		3/877 (0.3%)
Pharyngitis bacterial	1/886 (0.1%)		1/877 (0.1%)
Plasmodium falciparum infection	2/886 (0.2%)		0/877 (0%)
Plasmodium malariae infection	3/886 (0.3%)		0/877 (0%)
Pneumocystis jirovecii pneumonia	1/886 (0.1%)		2/877 (0.2%)
Pneumonia	16/886 (1.8%)		11/877 (1.3%)
Pneumonia bacterial	7/886 (0.8%)		1/877 (0.1%)
Pneumonia viral	1/886 (0.1%)		0/877 (0%)
Post procedural infection	1/886 (0.1%)		0/877 (0%)
Postoperative wound infection	1/886 (0.1%)		0/877 (0%)
Progressive multifocal leukoencephalopathy	0/886 (0%)		1/877 (0.1%)
Pulmonary sepsis	1/886 (0.1%)		0/877 (0%)
Pulmonary tuberculosis	4/886 (0.5%)		7/877 (0.8%)
Pyelonephritis	2/886 (0.2%)		2/877 (0.2%)
Pyelonephritis acute	2/886 (0.2%)		1/877 (0.1%)
Respiratory tract infection	0/886 (0%)		2/877 (0.2%)
Secondary syphilis	1/886 (0.1%)		0/877 (0%)
Sepsis	3/886 (0.3%)		2/877 (0.2%)
Septic shock	1/886 (0.1%)		0/877 (0%)
Sinusitis	1/886 (0.1%)		1/877 (0.1%)
Subcutaneous abscess	0/886 (0%)		1/877 (0.1%)
Tonsillitis	2/886 (0.2%)		3/877 (0.3%)
Tonsillitis bacterial	0/886 (0%)		1/877 (0.1%)
Tooth infection	2/886 (0.2%)		0/877 (0%)
Tracheobronchitis	2/886 (0.2%)		0/877 (0%)
Tuberculosis	1/886 (0.1%)		1/877 (0.1%)
Tuberculosis gastrointestinal	0/886 (0%)		1/877 (0.1%)
Tuberculous pleurisy	1/886 (0.1%)		0/877 (0%)
Tubo-ovarian abscess	0/886 (0%)		1/877 (0.1%)
Typhoid fever	2/886 (0.2%)		1/877 (0.1%)
Upper respiratory tract infection	2/886 (0.2%)		3/877 (0.3%)
Upper respiratory tract infection bacterial	0/886 (0%)		1/877 (0.1%)
Urinary tract infection	5/886 (0.6%)		3/877 (0.3%)
Viral infection	0/886 (0%)		4/877 (0.5%)
Viral upper respiratory tract infection	1/886 (0.1%)		0/877 (0%)
Vulval abscess	0/886 (0%)		1/877 (0.1%)
Injury, poisoning and procedural complications
Abdominal injury	1/886 (0.1%)		0/877 (0%)
Alcohol poisoning	0/886 (0%)		1/877 (0.1%)
Ankle fracture	1/886 (0.1%)		0/877 (0%)
Arthropod bite	1/886 (0.1%)		0/877 (0%)
Chemical poisoning	1/886 (0.1%)		0/877 (0%)
Clavicle fracture	0/886 (0%)		2/877 (0.2%)
Concussion	1/886 (0.1%)		1/877 (0.1%)
Contusion	1/886 (0.1%)		0/877 (0%)
Dislocation of vertebra	0/886 (0%)		1/877 (0.1%)
Exposure to toxic agent	1/886 (0.1%)		0/877 (0%)
Foot fracture	1/886 (0.1%)		0/877 (0%)
Forearm fracture	2/886 (0.2%)		0/877 (0%)
Gun shot wound	1/886 (0.1%)		0/877 (0%)
Hair injury	1/886 (0.1%)		0/877 (0%)
Hand fracture	1/886 (0.1%)		2/877 (0.2%)
Head injury	0/886 (0%)		3/877 (0.3%)
Humerus fracture	1/886 (0.1%)		0/877 (0%)
Injury	2/886 (0.2%)		0/877 (0%)
Joint dislocation	2/886 (0.2%)		0/877 (0%)
Joint injury	1/886 (0.1%)		0/877 (0%)
Laceration	2/886 (0.2%)		0/877 (0%)
Limb injury	2/886 (0.2%)		2/877 (0.2%)
Lower limb fracture	1/886 (0.1%)		0/877 (0%)
Overdose	1/886 (0.1%)		0/877 (0%)
Poisoning	1/886 (0.1%)		0/877 (0%)
Post procedural diarrhoea	0/886 (0%)		1/877 (0.1%)
Procedural dizziness	0/886 (0%)		1/877 (0.1%)
Procedural pain	0/886 (0%)		1/877 (0.1%)
Procedural vomiting	0/886 (0%)		1/877 (0.1%)
Radius fracture	1/886 (0.1%)		1/877 (0.1%)
Rib fracture	1/886 (0.1%)		0/877 (0%)
Skin abrasion	1/886 (0.1%)		1/877 (0.1%)
Skull fracture	1/886 (0.1%)		0/877 (0%)
Snake bite	0/886 (0%)		1/877 (0.1%)
Soft tissue injury	0/886 (0%)		1/877 (0.1%)
Spinal compression fracture	1/886 (0.1%)		0/877 (0%)
Subdural haematoma	0/886 (0%)		1/877 (0.1%)
Tibia fracture	0/886 (0%)		1/877 (0.1%)
Traumatic haemorrhage	1/886 (0.1%)		0/877 (0%)
Upper limb fracture	3/886 (0.3%)		0/877 (0%)
Investigations
Alanine aminotransferase increased	20/886 (2.3%)		19/877 (2.2%)
Aspartate aminotransferase increased	32/886 (3.6%)		29/877 (3.3%)
Blood albumin decreased	6/886 (0.7%)		9/877 (1%)
Blood alkaline phosphatase increased	0/886 (0%)		1/877 (0.1%)
Blood bicarbonate decreased	1/886 (0.1%)		1/877 (0.1%)
Blood bilirubin increased	68/886 (7.7%)		42/877 (4.8%)
Blood cholesterol increased	1/886 (0.1%)		0/877 (0%)
Blood creatinine increased	0/886 (0%)		7/877 (0.8%)
Blood glucose increased	1/886 (0.1%)		1/877 (0.1%)
Blood phosphorus decreased	73/886 (8.2%)		86/877 (9.8%)
Blood phosphorus increased	0/886 (0%)		2/877 (0.2%)
Blood potassium decreased	3/886 (0.3%)		1/877 (0.1%)
Blood potassium increased	2/886 (0.2%)		0/877 (0%)
Blood pressure increased	0/886 (0%)		1/877 (0.1%)
Blood sodium decreased	8/886 (0.9%)		8/877 (0.9%)
Blood sodium increased	3/886 (0.3%)		2/877 (0.2%)
Blood triglycerides increased	2/886 (0.2%)		2/877 (0.2%)
Haemoglobin decreased	15/886 (1.7%)		18/877 (2.1%)
Hepatic enzyme increased	1/886 (0.1%)		1/877 (0.1%)
Liver function test abnormal	0/886 (0%)		2/877 (0.2%)
Low density lipoprotein increased	2/886 (0.2%)		2/877 (0.2%)
Neutrophil count decreased	64/886 (7.2%)		80/877 (9.1%)
Platelet count decreased	8/886 (0.9%)		19/877 (2.2%)
Transaminases increased	6/886 (0.7%)		9/877 (1%)
White blood cell count decreased	1/886 (0.1%)		1/877 (0.1%)
Metabolism and nutrition disorders
Abnormal loss of weight	75/886 (8.5%)		54/877 (6.2%)
Decreased appetite	2/886 (0.2%)		5/877 (0.6%)
Diabetes mellitus	3/886 (0.3%)		5/877 (0.6%)
Diabetic ketoacidosis	1/886 (0.1%)		1/877 (0.1%)
Dyslipidaemia	8/886 (0.9%)		6/877 (0.7%)
Hypercholesterolaemia	2/886 (0.2%)		1/877 (0.1%)
Hyperglycaemia	4/886 (0.5%)		5/877 (0.6%)
Hyperkalaemia	2/886 (0.2%)		3/877 (0.3%)
Hypernatraemia	2/886 (0.2%)		1/877 (0.1%)
Hyperphosphataemia	0/886 (0%)		1/877 (0.1%)
Hypertriglyceridaemia	4/886 (0.5%)		0/877 (0%)
Hypoalbuminaemia	0/886 (0%)		2/877 (0.2%)
Hypoglycaemia	3/886 (0.3%)		0/877 (0%)
Hypokalaemia	0/886 (0%)		1/877 (0.1%)
Hyponatraemia	2/886 (0.2%)		4/877 (0.5%)
Hypophosphataemia	42/886 (4.7%)		43/877 (4.9%)
Lactic acidosis	0/886 (0%)		1/877 (0.1%)
Metabolic acidosis	0/886 (0%)		1/877 (0.1%)
Obesity	1/886 (0.1%)		1/877 (0.1%)
Type 2 diabetes mellitus	2/886 (0.2%)		5/877 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	3/886 (0.3%)		1/877 (0.1%)
Flank pain	1/886 (0.1%)		0/877 (0%)
Hypercreatinaemia	0/886 (0%)		1/877 (0.1%)
Intervertebral disc protrusion	0/886 (0%)		2/877 (0.2%)
Myalgia	1/886 (0.1%)		0/877 (0%)
Pain in extremity	0/886 (0%)		2/877 (0.2%)
Plantar fasciitis	0/886 (0%)		1/877 (0.1%)
Spinal osteoarthritis	0/886 (0%)		1/877 (0.1%)
Systemic lupus erythematosus	1/886 (0.1%)		1/877 (0.1%)
Trigger finger	0/886 (0%)		1/877 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	0/886 (0%)		1/877 (0.1%)
B-cell lymphoma	0/886 (0%)		1/877 (0.1%)
Benign hydatidiform mole	2/886 (0.2%)		0/877 (0%)
Breast cancer	0/886 (0%)		1/877 (0.1%)
Cervix carcinoma	2/886 (0.2%)		0/877 (0%)
Choriocarcinoma	0/886 (0%)		1/877 (0.1%)
Colon adenoma	0/886 (0%)		1/877 (0.1%)
Colorectal adenocarcinoma	1/886 (0.1%)		0/877 (0%)
Hepatocellular carcinoma	1/886 (0.1%)		1/877 (0.1%)
Hodgkin's disease	1/886 (0.1%)		0/877 (0%)
Non-Hodgkin's lymphoma	1/886 (0.1%)		0/877 (0%)
Phyllodes tumour	1/886 (0.1%)		0/877 (0%)
Rectal adenocarcinoma	0/886 (0%)		1/877 (0.1%)
Uterine leiomyoma	3/886 (0.3%)		2/877 (0.2%)
Nervous system disorders
Ataxia	2/886 (0.2%)		0/877 (0%)
Carpal tunnel syndrome	0/886 (0%)		1/877 (0.1%)
Central nervous system lesion	0/886 (0%)		1/877 (0.1%)
Cerebral atrophy	0/886 (0%)		1/877 (0.1%)
Cerebrovascular accident	1/886 (0.1%)		2/877 (0.2%)
Diplegia	1/886 (0.1%)		0/877 (0%)
Dizziness	14/886 (1.6%)		8/877 (0.9%)
Dizziness postural	0/886 (0%)		1/877 (0.1%)
Epilepsy	1/886 (0.1%)		1/877 (0.1%)
Febrile convulsion	1/886 (0.1%)		0/877 (0%)
Haemorrhagic stroke	0/886 (0%)		1/877 (0.1%)
Headache	3/886 (0.3%)		6/877 (0.7%)
Intracranial venous sinus thrombosis	1/886 (0.1%)		0/877 (0%)
Loss of consciousness	0/886 (0%)		1/877 (0.1%)
Migraine	0/886 (0%)		2/877 (0.2%)
Neuropathy peripheral	0/886 (0%)		1/877 (0.1%)
Paraplegia	0/886 (0%)		1/877 (0.1%)
Polyneuropathy	1/886 (0.1%)		0/877 (0%)
Seizure	1/886 (0.1%)		0/877 (0%)
Somnolence	3/886 (0.3%)		1/877 (0.1%)
Subarachnoid haemorrhage	0/886 (0%)		1/877 (0.1%)
Syncope	0/886 (0%)		1/877 (0.1%)
Tonic convulsion	0/886 (0%)		1/877 (0.1%)
Transient ischaemic attack	1/886 (0.1%)		0/877 (0%)
Tremor	0/886 (0%)		1/877 (0.1%)
VIIth nerve paralysis	1/886 (0.1%)		0/877 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion	1/886 (0.1%)		0/877 (0%)
Abortion complete	1/886 (0.1%)		1/877 (0.1%)
Abortion incomplete	6/886 (0.7%)		7/877 (0.8%)
Abortion missed	2/886 (0.2%)		3/877 (0.3%)
Abortion spontaneous	9/886 (1%)		16/877 (1.8%)
Abortion spontaneous incomplete	1/886 (0.1%)		1/877 (0.1%)
Abortion threatened	1/886 (0.1%)		0/877 (0%)
Cephalo-pelvic disproportion	1/886 (0.1%)		0/877 (0%)
Ectopic pregnancy	0/886 (0%)		4/877 (0.5%)
False labour	0/886 (0%)		1/877 (0.1%)
Foetal death	3/886 (0.3%)		2/877 (0.2%)
Gestational hypertension	0/886 (0%)		1/877 (0.1%)
Haemorrhage in pregnancy	0/886 (0%)		1/877 (0.1%)
Placenta praevia	0/886 (0%)		1/877 (0.1%)
Pre-eclampsia	1/886 (0.1%)		0/877 (0%)
Premature baby	0/886 (0%)		1/877 (0.1%)
Premature labour	0/886 (0%)		1/877 (0.1%)
Premature rupture of membranes	1/886 (0.1%)		1/877 (0.1%)
Ruptured ectopic pregnancy	0/886 (0%)		2/877 (0.2%)
Stillbirth	4/886 (0.5%)		1/877 (0.1%)
Psychiatric disorders
Acute psychosis	1/886 (0.1%)		1/877 (0.1%)
Acute stress disorder	1/886 (0.1%)		0/877 (0%)
Aggression	1/886 (0.1%)		0/877 (0%)
Anxiety	1/886 (0.1%)		0/877 (0%)
Bipolar disorder	1/886 (0.1%)		0/877 (0%)
Brief psychotic disorder, with postpartum onset	0/886 (0%)		1/877 (0.1%)
Completed suicide	5/886 (0.6%)		3/877 (0.3%)
Confusional state	1/886 (0.1%)		0/877 (0%)
Depressed mood	1/886 (0.1%)		0/877 (0%)
Depression	4/886 (0.5%)		4/877 (0.5%)
Drug abuse	0/886 (0%)		1/877 (0.1%)
Hallucination	1/886 (0.1%)		1/877 (0.1%)
Homicidal ideation	1/886 (0.1%)		0/877 (0%)
Insomnia	2/886 (0.2%)		2/877 (0.2%)
Intentional self-injury	0/886 (0%)		1/877 (0.1%)
Major depression	4/886 (0.5%)		3/877 (0.3%)
Mental disorder	1/886 (0.1%)		0/877 (0%)
Psychotic disorder	3/886 (0.3%)		0/877 (0%)
Suicidal ideation	12/886 (1.4%)		5/877 (0.6%)
Suicide attempt	8/886 (0.9%)		5/877 (0.6%)
Violence-related symptom	1/886 (0.1%)		0/877 (0%)
Renal and urinary disorders
Acute kidney injury	2/886 (0.2%)		0/877 (0%)
Calculus ureteric	2/886 (0.2%)		0/877 (0%)
Chronic kidney disease	0/886 (0%)		1/877 (0.1%)
Haematuria	0/886 (0%)		3/877 (0.3%)
Hydronephrosis	1/886 (0.1%)		0/877 (0%)
Nephrolithiasis	2/886 (0.2%)		4/877 (0.5%)
Nephrotic syndrome	1/886 (0.1%)		0/877 (0%)
Renal colic	2/886 (0.2%)		0/877 (0%)
Renal failure	0/886 (0%)		2/877 (0.2%)
Urogenital fistula	0/886 (0%)		1/877 (0.1%)
Reproductive system and breast disorders
Cervical dysplasia	3/886 (0.3%)		1/877 (0.1%)
Dysfunctional uterine bleeding	3/886 (0.3%)		0/877 (0%)
Dysmenorrhoea	1/886 (0.1%)		0/877 (0%)
Erectile dysfunction	1/886 (0.1%)		0/877 (0%)
Gynaecomastia	3/886 (0.3%)		0/877 (0%)
Menorrhagia	4/886 (0.5%)		5/877 (0.6%)
Menstrual disorder	0/886 (0%)		1/877 (0.1%)
Metrorrhagia	3/886 (0.3%)		2/877 (0.2%)
Ovarian cyst	2/886 (0.2%)		2/877 (0.2%)
Pelvic pain	0/886 (0%)		1/877 (0.1%)
Postmenopausal haemorrhage	0/886 (0%)		1/877 (0.1%)
Uterine haemorrhage	2/886 (0.2%)		0/877 (0%)
Vulvovaginal swelling	0/886 (0%)		1/877 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/886 (0.2%)		4/877 (0.5%)
Dyspnoea	0/886 (0%)		1/877 (0.1%)
Interstitial lung disease	0/886 (0%)		1/877 (0.1%)
Pharyngeal mass	0/886 (0%)		1/877 (0.1%)
Pleurisy	1/886 (0.1%)		0/877 (0%)
Pulmonary embolism	1/886 (0.1%)		1/877 (0.1%)
Skin and subcutaneous tissue disorders
Cutaneous lupus erythematosus	0/886 (0%)		1/877 (0.1%)
Decubitus ulcer	1/886 (0.1%)		0/877 (0%)
Lipodystrophy acquired	3/886 (0.3%)		0/877 (0%)
Rash	3/886 (0.3%)		3/877 (0.3%)
Rash generalised	1/886 (0.1%)		0/877 (0%)
Urticaria	1/886 (0.1%)		1/877 (0.1%)
Social circumstances
Victim of homicide	0/886 (0%)		1/877 (0.1%)
Vascular disorders
Deep vein thrombosis	7/886 (0.8%)		5/877 (0.6%)
Diabetic vascular disorder	0/886 (0%)		1/877 (0.1%)
Hypertension	8/886 (0.9%)		9/877 (1%)
Systolic hypertension	0/886 (0%)		1/877 (0.1%)
Thromboangiitis obliterans	0/886 (0%)		1/877 (0.1%)
Thrombophlebitis superficial	0/886 (0%)		1/877 (0.1%)
Other (Not Including Serious) Adverse Events
	Early-ART		Delayed-ART
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/886 (0%)		0/877 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All study abstracts and publications are subject to HPTN Publication and Public Information Policies and Clinical Trial Agreements between NIAID (DAIDS) and company collaborators. The publication or other disclosure can be delayed for up to thirty additional business days for manuscripts and five business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.