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Preventing Sexual Transmission of HIV With Anti-HIV Drugs

This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), May 2008

Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
HIV Prevention Trials Network
Information provided by: 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 III

MedlinePlus related topics:   AIDS    AIDS Medicines   

ChemIDplus related topics:   Zidovudine    Lamivudine    Didanosine    Stavudine    Efavirenz    Ritonavir    Nevirapine    Lopinavir    Atazanavir sulfate    BMS 232632    Tenofovir    Tenofovir disoproxil    Tenofovir Disoproxil Fumarate    Truvada    Combivir   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Prevention, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Efficacy Study
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

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 Study Completion Date:   February 2011
Estimated Primary Completion Date:   February 2011 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Experimental
Participants will begin ART in addition to receiving HIV primary care
Drug: Atazanavir
300 mg taken orally once daily
Drug: Didanosine
400 mg taken orally once daily
Drug: Efavirenz
600 mg taken orally once daily
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily
Drug: Lamivudine
300 mg taken orally once daily
Drug: Lopinavir/Ritonavir
200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily
Drug: Nevirapine
200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily
Drug: Stavudine
Dosage depends on weight
Drug: Tenofovir disoproxil fumarate
300 mg taken orally once daily
Drug: Zidovudine/Lamivudine
150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily
2: Experimental
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.
Drug: Atazanavir
300 mg taken orally once daily
Drug: Didanosine
400 mg taken orally once daily
Drug: Efavirenz
600 mg taken orally once daily
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily
Drug: Lamivudine
300 mg taken orally once daily
Drug: Lopinavir/Ritonavir
200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily
Drug: Nevirapine
200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily
Drug: Stavudine
Dosage depends on weight
Drug: Tenofovir disoproxil fumarate
300 mg taken orally once daily
Drug: Zidovudine/Lamivudine
150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily

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.

  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 Center     Recruiting
      Boston, Massachusetts, United States, 02115
      Contact: Robbie Singal, MPHTM     617-927-6021     rsingal@fenwayhealth.org    
Brazil
Instituto de Pesquisa Clinica Evandro Chagas     Recruiting
      Rio de Janeiro, Brazil, 21045-900
      Contact: Beatriz Grinsztejn, MD, PhD     552 125 644933     gbeatriz@unisys.com.br    
Hospital Geral de Nova Iguacu     Recruiting
      Rio de Janeiro, Brazil, 21045-900
      Contact: Jose Henrique Pilotto, MD     552 122 707064     pilotto@unisys.com.br    
Hospital dos Servidores do Estado - Servico de Doe     Active, not recruiting
      Saude, Rio de Janeiro, Brazil, 20221-903
Brazil, RS
Hospital Nossa Senhora da Conceicao     Recruiting
      Port Alegre, RS, Brazil, 91350 200
      Contact: Breno Riegel Santos, MD     55 51 3361 2911     breno@ghc.com.br    
India
National AIDS Research Institute, Pune, India     Recruiting
      Pune, India
      Contact: Manisha Ghate     91-20-712-1072     mghate@nari-icmr.res.in    
Talera Municipal Hospital - NARI Clinic     Recruiting
      Pune, India
      Contact: Manisha Ghate     91-20-712-1072     mghate@nari-icmr.res.in    
Gadikhana Hospital - NARI Clinic     Recruiting
      Pune, India
      Contact: Manisha Ghate     91-20-712-1072     mghate@nari-icmr.res.in    
Jehangir Hospital and Medical Center - NARI Clinic     Recruiting
      Pune, India
      Contact: Manisha Ghate     91-20-712-1072     mghate@nari-icmr.res.in    
Y.R. Gaitonde Medical and Research Foundation, India     Recruiting
      Taramani, India
      Contact: A. K. Krishnan     011-91-44-22542929        
Malawi
Ministry of Health & Population, Lilongwe Central     Recruiting
      Lilongwe, Malawi
      Contact: David Chilongozi, MPH     01 265 755056     dchilongozi@malawi.net    
Malawi College of Medicine, Queen Elizabeth Central Hospital     Recruiting
      Blantyre, Malawi
      Contact: Newton Kumwenda, MPH, PhD     265 163 1527     jhopkins@sdnp.org.mw    
Thailand
Research Institute for Health Sciences (RIHES)     Recruiting
      Chaing Mai, Thailand, 50202
      Contact: Peter Lange     66-53-221-966        
Family Health Center, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai Univ.     Recruiting
      Chiang Mai, Thailand, 50200
      Contact: Cholticha Ruangyuttikarn     66-53 221-966 ext 465     cholti@chiangmai.ac.th    

Sponsors and Collaborators

Investigators
Study Chair:     Myron S. Cohen, MD     The University of North Carolina, Chapel Hill    
  More 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
 
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Publications:

Responsible Party:   DAIDS ( Rona Siskind )
Study ID Numbers:   HPTN 052
First Received:   December 16, 2003
Last Updated:   August 7, 2008
ClinicalTrials.gov Identifier:   NCT00074581
Health Authority:   United States: Food and Drug Administration

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

Study placed in the following topic categories:
Efavirenz
Sexually Transmitted Diseases, Viral
Stavudine
Acquired Immunodeficiency Syndrome
Zidovudine
Lamivudine
Atazanavir
Immunologic Deficiency Syndromes
Virus Diseases
Nevirapine
Didanosine
Lopinavir
Emtricitabine
Ritonavir
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 10, 2008




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