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Preventing Sexual Transmission of HIV With Anti-HIV Drugs

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
HIV Prevention Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00074581
First received: December 16, 2003
Last updated: November 20, 2014
Last verified: November 2014
  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: May 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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
HSE-Hospital dos Servidores do Estado CRS
Rio de Janeiro, Brazil, 20221-903
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, Brazil
India
NARI Clinic at NIV CRS
Pune, Maharashtra, India
NARI Clinic at Gadikhana Dr. Kotnis Municipal Dispensary CRS
Pune, Maharashtra, India
NARI Pune 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
HIV Prevention Trials Network
Investigators
Study Chair: Myron S. Cohen, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: November 20, 2014
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Lamivudine
Lopinavir
Ritonavir
Tenofovir
Tenofovir disoproxil
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014