HIV Infections
Conditions
Keywords
HIV Infections, HIV Seronegativity
Brief summary
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
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.
Interventions
DRUGDidanosine
400 mg taken orally once daily
DRUGEfavirenz
600 mg taken orally once daily
DRUGEmtricitabine/Tenofovir disoproxil fumarate
200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily
DRUGAtazanavir
300 mg taken orally once daily
DRUGLamivudine
300 mg taken orally once daily
DRUGLopinavir/Ritonavir
200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily
DRUGNevirapine
200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily
DRUGStavudine
Dosage depends on weight
DRUGTenofovir disoproxil fumarate
300 mg taken orally once daily
150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily
Sponsors
HIV Prevention Trials Network
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | Throughout study | 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. |
| All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | Throughout study | 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. |
Countries
Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, United States, Zimbabwe
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early-ART Participants will begin ART in addition to receiving HIV primary care
Atazanavir: 300 mg taken orally once daily
Didanosine: 400 mg taken orally once daily
Efavirenz: 600 mg taken orally once daily
Emtricitabine/Tenofovir disoproxil fumarate: 200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily
Lamivudine: 300 mg taken orally once daily
Lopinavir/Ritonavir: 200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily
Nevirapine: 200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily
Stavudine: Dosage depends on weight
Tenofovir disoproxil fumarate: 300 mg taken orally once daily
Zidovudine/Lamivudine: 150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily
Note: Sites could also use locally supplied, FDA-approved drugs if they could be purchased with nonstudy funds. For participants with virologic failure, specified second-line treatment regimens were provided. | 1,789 |
| Delayed-ART 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.
(Same drug regimen as that described in the early-ART arm)
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. | 1,767 |
| Total | 3,556 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 15 | 16 |
| Overall Study | Ended relationship w. index participant | 117 | 106 |
| Overall Study | Lost to Follow-up | 16 | 11 |
| Overall Study | Other | 14 | 19 |
| Overall Study | Relocated | 14 | 9 |
| Overall Study | Unable to adhere to visit schedule | 13 | 14 |
| Overall Study | Were withdrawn by investigator | 5 | 2 |
| Overall Study | Withdrawal by Subject | 50 | 49 |
Baseline characteristics
| Characteristic | Early-ART | Delayed-ART | Total |
|---|---|---|---|
| Age, Customized 18-25 yr | 300 participants | 335 participants | 635 participants |
| Age, Customized 26-40 yr | 1101 participants | 1079 participants | 2180 participants |
| Age, Customized >40 yr | 388 participants | 353 participants | 741 participants |
| Region Africa | 961 participants | 960 participants | 1921 participants |
| Region Asia | 535 participants | 528 participants | 1063 participants |
| Region North or South America | 293 participants | 279 participants | 572 participants |
| Sex: Female, Male Female | 877 Participants | 860 Participants | 1737 Participants |
| Sex: Female, Male Male | 912 Participants | 907 Participants | 1819 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 886 | 0 / 877 |
| serious Total, serious adverse events | 526 / 886 | 522 / 877 |
Outcome results
Primary
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.
Time frame: Throughout study
Population: Population includes all partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases, by arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Early-ART | All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | 0.44 event rate per 100 person-yr |
| Delayed-ART | All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | 1.41 event rate per 100 person-yr |
p-value: <0.000195% CI: [0.19, 0.53]Regression, Cox
Primary
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.
Time frame: Throughout study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Early-ART | Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | 0.07 event rate per 100 person-yr |
| Delayed-ART | Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms | 1.03 event rate per 100 person-yr |
p-value: <0.000195% CI: [0.02, 0.22]Regression, Cox