Preventing Sexual Transmission of HIV With Anti-HIV Drugs - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	HIV Prevention Trials Network
Information provided by (Responsible Party):	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00074581

Purpose

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	Intervention	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) 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

Resource links provided by NLM:

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Recorded HIV infections in Arms 1 and 2 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time from enrollment to death [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Immunologic response of HIV infected partner: CD4 count over time, time from enrollment to immunologic failure, time from initiation of ART to immunologic failure, time from initiation of secondary regimen to immunologic failure [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Viral load in blood, semen, and vaginal secretions [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time to initiation of secondary regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Safety and toxicity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
HIV drug resistance: prevalence of drug resistance, proportion of HIV infected partners acquiring a drug resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time from enrollment to the time of first development and subsequent development of STDs [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Adherence to drug regimen over time [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Sexual behavior over time following initiation of starting regimen and following initiation of a secondary regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Quality of life indicators over time following initiation of starting regimen and following initiation of a secondary regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Determine, characterize, and compare the effect of circumcision on HIV transmission in different geographic setting and by antiretroviral treatment strategies. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	3500
Study Start Date:	February 2005
Estimated Primary Completion Date:	April 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will begin ART in addition to receiving HIV primary care	Drug: Atazanavir 300 mg taken orally once daily Other Name: Reyataz Drug: Didanosine 400 mg taken orally once daily Other Name: Videx Drug: Efavirenz 600 mg taken orally once daily Other Name: Sustiva Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Other Name: 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 Name: 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 Name: 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 Name: Reyataz Drug: Didanosine 400 mg taken orally once daily Other Name: Videx Drug: Efavirenz 600 mg taken orally once daily Other Name: Sustiva Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily Other Name: 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 Name: 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 Name: Combivir

Arms

Assigned Interventions

Experimental: 1

Participants will begin ART in addition to receiving HIV primary care

Drug: Atazanavir

300 mg taken orally once daily

Other Name: Reyataz

Drug: Didanosine

400 mg taken orally once daily

Other Name: Videx

Drug: Efavirenz

600 mg taken orally once daily

Other Name: Sustiva

Drug: Emtricitabine/Tenofovir disoproxil fumarate

200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily

Other Name: 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 Name: 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 Name: 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 Name: Reyataz

Drug: Didanosine

400 mg taken orally once daily

Other Name: Videx

Drug: Efavirenz

600 mg taken orally once daily

Other Name: Sustiva

Drug: Emtricitabine/Tenofovir disoproxil fumarate

200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily

Other Name: 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 Name: 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 Name: Combivir

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074581

Locations

United States, Massachusetts
Fenway Community Health Ctr. CRS
Boston, Massachusetts, United States, 02115
Botswana
Gaborone Prevention/Treatment Trials CRS
Gaborone, Botswana
Brazil
Hospital Geral de Nova Iguaçu CRS (HGNI CRS)
Nova Iguacu, Rio de Janeiro, Brazil
Hospital Nossa Senhora da Conceicao CRS
Port Alegre, Rio Grande do Sul, Brazil, 91350 200
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, Brazil
HSE-Hospital dos Servidores do Estado CRS
Rio de Janeiro, Brazil, 20221-903
India
NARI Clinic at NIV CRS
Pune, Maharashtra, India
NARI Pune CRS
Pune, Maharashtra, India
NARI Clinic at Gadikhana Dr. Kotnis Municipal Dispensary CRS
Pune, Maharashtra, India
YRG CARE Medical Ctr., VHS Chennai CRS
Taramani, India
Kenya
Kemri/Cdc Crs
Kisumu, Kenya
Malawi
College of Med. JHU CRS
Blantyre, Malawi
University of North Carolina Lilongwe CRS
Lilongwe, Malawi
South Africa
Soweto HPTN CRS
Johannesburg, Gauteng, South Africa
Wits HIV CRS
Johannesburg, Gauteng, South Africa
Thailand
Chiang Mai Univ. AIDS Prevention CRS
Chiang Mai, Thailand, 50202
Zimbabwe
UZ-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

More Information

Additional Information:

Click here for more information about atazanavir This link exits the ClinicalTrials.gov site

Click here for more information about didanosine This link exits the ClinicalTrials.gov site

Click here for more information about efavirenz This link exits the ClinicalTrials.gov site

Click here for more information about emtricitabine/tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about lamivudine This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information about nevirapine This link exits the ClinicalTrials.gov site

Click here for more information about stavudine This link exits the ClinicalTrials.gov site

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about zidovudine/lamivudine This link exits the ClinicalTrials.gov site

Click here for more information on understanding HIV prevention This link exits the ClinicalTrials.gov site

Haga clic aqui para ver informacion sobre este ensayo clinico en espanol. This link exits the ClinicalTrials.gov site

Publications:

Chan DJ. Fatal attraction: sex, sexually transmitted infections and HIV-1. Int J STD AIDS. 2006 Oct;17(10):643-51. Review.

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.

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. No abstract available.

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. No abstract available.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. Epub 2011 Jul 18.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00074581 History of Changes
Other Study ID Numbers:	HPTN 052, 10068
Study First Received:	December 16, 2003
Last Updated:	April 6, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

HIV Infections
HIV Seronegativity

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Didanosine
Zidovudine
Stavudine
Nevirapine

Lamivudine
Tenofovir disoproxil
Tenofovir
Efavirenz
Ritonavir
Anti-HIV Agents
Lopinavir
Atazanavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 21, 2012