HIV Infections
Conditions
Keywords
Acute Infection, Early HIV Infection, Short-Term Antiretroviral Therapy, Treatment Interruption, Antiretroviral Drug (ARV), ART
Brief summary
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
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.
Interventions
300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily
DRUGLopinavir/Ritonavir
Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Throughout study | set point is reached after the immune system has developed HIV antibodies and begins to attempt to fight the virus |
Countries
United States, Zimbabwe
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A Oral tenofovir/emcitribine (TDF/FTC) and lopinavir/ritonavir(LPV/RTV) 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. | 7 |
| Arm B Antiretroviral therapy (ART) will not be initiated until AIDS-defining illness occurs or if CD4 is confirmed at less than 350 mm\^3 at two separate, consecutive measurements | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Region of Enrollment United States | 3 participants | 4 participants | 7 participants |
| Region of Enrollment Zimbabwe | 4 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 7 | 5 / 9 |
| serious Total, serious adverse events | 1 / 7 | 1 / 9 |
Outcome results
Primary
Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome
Time frame: At Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 Week Treatment Arm Followed by Treatment Interruption | Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome | 1 participants |
| CD4 T Cell Guided Therapyh | Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome | 1 participants |
Primary
Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms
Time frame: At Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 12 Week Treatment Arm Followed by Treatment Interruption | Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms | 4.8627 Log 10 copies of virus/ml | Standard Deviation 0.9055 |
| CD4 T Cell Guided Therapyh | Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms | 4.2620 Log 10 copies of virus/ml | Standard Deviation 1.0867 |
Primary
Viral Set Point
set point is reached after the immune system has developed HIV antibodies and begins to attempt to fight the virus
Time frame: Throughout study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 12 Week Treatment Arm Followed by Treatment Interruption | Viral Set Point | 4.8627 Log 10 copies virus/ml | Standard Deviation 0.9055 |
| CD4 T Cell Guided Therapyh | Viral Set Point | 4.2434 Log 10 copies virus/ml | Standard Deviation 0.7992 |