Safety and Effectiveness of Short-Term Anti-HIV Drug Therapy for Recent HIV-1 Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of an anti-HIV drug regimen followed by treatment interruption in people recently infected with HIV. This study will also compare the effects of a treatment regimen including treatment interruption with a treatment plan based on clinical indicators.

Detailed Description
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About 6 months after infection, HIV viral load reaches a temporarily stable level known as virus set point. Virus set point is different for each patient and can be a predictor for disease progression. Preliminary studies indicate that early, short-term antiretroviral therapy (ART) given to people newly infected with HIV may lead to lower virus set points and preserved CD4 counts. However, the length of short-term treatment needed to balance the possible adverse effects of ART with the achievement of lower virus set point is not yet known. By lowering the virus set point and maintaining CD4 counts, the need for long-term ART may be postponed. The purpose of this study is to determine the safety and efficacy of a short course of ART on producing a lower virus set point in adults recently infected with HIV. This study will last at least 28 weeks. Participants will be randomly assigned to one of two arms. Arm A will receive ART for 12 weeks as emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) daily and lopinavir/ritonavir (LPV/RTV) in tablet form twice daily. After 12 weeks, treatment will be interrupted unless the CD4 count is measured to be less than 350 cells/mm^3 on two consecutive occasions during treatment interruption. If that occurs therapy will be resumed. Participants in Arm B will receive no treatment until cluster of differentiation 4 (CD4) counts drop below 350 cells/mm^3, indicating ART is needed. Study visits will occur at study entry, at Weeks 2 and 4, and every 4 weeks thereafter. At each study visit, a physical exam, blood collection, and completion of an adherence questionnaire will occur. Participants are encouraged to enroll in a related substudy that will evaluate HIV viral load in genital secretions.

Official Title
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An Open-Label Randomized Clinical Trial to Evaluate the Efficacy and Safety of Short Course Antiretroviral Therapy for Acute or Recent HIV-1 Infection in Zimbabwe and the United States

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Tenofovir disoproxil fumarate/Emtricitabine
* Drug: Lopinavir/Ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute or recent HIV-1 infection. More information about this criterion can be found in the protocol. CD4 count 500 cells/mm3 or greater No evidence of prior or current AIDS-defining illness No signs or symptoms of HIV infection or AIDS-defining illness that, in the opinion of the investigator, requires ART Willing to use acceptable forms of contraception Exclusion Criteria: Prior treatment with any antiretroviral drug for more than 7 days Use of certain drugs within 21 days of study entry Prior receipt of investigational anti-HIV-1 vaccine Ongoing therapy with systemic corticosteroids, chemotherapeutic agents, nephrotoxic systemic agents, immunomodulatory treatments, or investigational agents Known allergy/sensitivity to study drugs or their formulations Current drug or alcohol use or abuse that, in the opinion of the investigator, may interfere with the study Serious medical or psychiatric illness that may interfere with the study Hepatitis B infected Pregnancy or breastfeeding

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment interruption<br>Oral Tenofovir disoproxil fumarate/Emtricitabine and Lopinavir/Ritonavir for 12 weeks followed by treatment interruption if CD4 count is 450 mm^3 or higher. When CD4 count is less than 350 mm^3 on two separate, consecutive measurements during treatment interruption, therapy will be resumed. | Drug: Tenofovir disoproxil fumarate/Emtricitabine<br>* 300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily<br>* Other names: TDF/FTC;Drug: Lopinavir/Ritonavir<br>* Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily<br>* Other names: LPV/RTV;|
| Experimental: CD4 T cell guided therapy<br>Anti Retroviral Therapy initiated when AIDS-defining illness occurs or if CD4 count is confirmed at less than 350 mm^3 at two separate, consecutive measurements | Drug: Tenofovir disoproxil fumarate/Emtricitabine<br>* 300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily<br>* Other names: TDF/FTC;Drug: Lopinavir/Ritonavir<br>* Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily<br>* Other names: LPV/RTV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms |  | At Week 24 | 
| Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome |  | At Week 24 | 
| Viral Set Point | set point is reached after the immune system has developed HIV antibodies and begins to attempt to fight the virus | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ART, Acute Infection, Early HIV Infection, Short-Term Antiretroviral Therapy, Treatment Interruption, Antiretroviral Drug (ARV)