Preventing Sexual Transmission of HIV With Anti-HIV Drugs

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will begin ART in addition to receiving HIV primary care | Drug: Atazanavir<br>* 300 mg taken orally once daily<br>* Other names: Reyataz;Drug: Didanosine<br>* 400 mg taken orally once daily<br>* Other names: Videx;Drug: Efavirenz<br>* 600 mg taken orally once daily<br>* Other names: Sustiva;Drug: Emtricitabine/Tenofovir disoproxil fumarate<br>* 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily<br>* Other names: Truvada;Drug: Lamivudine<br>* 300 mg taken orally once daily<br>* Other names: 3TC;Drug: Lopinavir/Ritonavir<br>* 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily<br>* Other names: Kaletra;Drug: Nevirapine<br>* 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily<br>* Other names: NVP;Drug: Stavudine<br>* Dosage depends on weight<br>* Other names: d4T;Drug: Tenofovir disoproxil fumarate<br>* 300 mg taken orally once daily<br>* Other names: TDF;Drug: Zidovudine/Lamivudine<br>* 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily<br>* Other names: Combivir;|
| Experimental: 2<br>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<br>* 300 mg taken orally once daily<br>* Other names: Reyataz;Drug: Didanosine<br>* 400 mg taken orally once daily<br>* Other names: Videx;Drug: Efavirenz<br>* 600 mg taken orally once daily<br>* Other names: Sustiva;Drug: Emtricitabine/Tenofovir disoproxil fumarate<br>* 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily<br>* Other names: Truvada;Drug: Lamivudine<br>* 300 mg taken orally once daily<br>* Other names: 3TC;Drug: Lopinavir/Ritonavir<br>* 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily<br>* Other names: Kaletra;Drug: Nevirapine<br>* 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily<br>* Other names: NVP;Drug: Stavudine<br>* Dosage depends on weight<br>* Other names: d4T;Drug: Tenofovir disoproxil fumarate<br>* 300 mg taken orally once daily<br>* Other names: TDF;Drug: Zidovudine/Lamivudine<br>* 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily<br>* Other names: Combivir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | 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. | Throughout study | 
| All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | 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. | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Infections, HIV Seronegativity