Acute HIV Infection - A Key Link for Transmission Prevention: A Randomized Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Proportion of Persons Agreeing to be Screened for Acute HIV Infection Among Those Offered Screening
研究概览
简要总结
This pilot study will assess the feasibility for the potential public health benefit of behavioral and antiretroviral interventions during acute HIV infection.
Central Hypothesis The investigators hypothesize that delivering behavioral and antiretroviral interventions to acutely infected persons will reduce onward transmission.
详细描述
The HIV epidemic in sub-Saharan Africa is severe and continues to grow. In urban areas of Malawi, 19% of pregnant women seeking antenatal care and 15.6% of Malawians aged 15-49 years were infected with HIV in 2007. Prevention interventions that prevent onward transmission of HIV are urgently needed.
Persons with acute HIV infection (AHI) may be responsible for a substantial proportion of onward transmission of HIV infection. AHI is characterized by unfettered replication of HIV in a "ramp up viremia". The high concentration of HIV in blood and genital secretions remains elevated for up to 10-12 weeks before it declines to the levels observed in established infection. These high levels of HIV shedding in the genital tract are likely to produce very efficient sexual transmission and the proportion of virions that are infectious may be substantially higher during acute compared to chronic infection. Consequently, the probability of transmission during unprotected intercourse for those with AHI is very high. Identifying persons with AHI and intervening to reduce onward transmission represents a tantalizing, but unproven, opportunity for HIV prevention.
To have maximal impact, a prevention program targeting AHI must identify a substantial number of acutely infected persons and intervene quickly to minimize onward transmission. An effective immediate intervention would require behavioral modification to limit sexual partners and unprotected sex acts, and a biological intervention to reduce infectious viral burden in genital secretions. This is the first study to pilot a combined behavioral and biomedical intervention in individuals with AHI to reduce onward transmission of HIV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary participants:
- •Acute HIV-1 infection
- •Men and women age greater than/= 18 years.
- •Intention to remain in the Lilongwe area for the duration of the study.
- •Ability and willingness of participant to provide informed consent.
- •Willingness to provide contact/locator information, be contacted, and asked to return for AHI results.
- •Partner Participants:
- •Referred by a primary participant and present with a referral card.
- •Had vaginal or anal sex with a primary participant within 12 weeks prior to that primary participant's enrolling
- •Men and women age greater than/=18 years.
- •remain in the Lilongwe area for the duration of the study.
- •Ability and willingness of participant to provide informed consent.
排除标准
- •Primary Participants:
- •HIV infection based on two positive HIV antibody rapid tests at the time of screening.
- •HIV-negative based on one or more antibody rapid test and an HIV RNA PCR test.
- •Serious illness, including tuberculosis or opportunistic infection, requiring systemic treatment and/or hospitalization.
- •Active drug or alcohol use or dependence.
- •Current imprisonment or involuntary incarceration.
- •Any other condition that in the opinion of the study investigator would compromise the safety of the study participant or study staff, or would prevent proper conduct of the study.
- •Partner Participants:
- •Active drug or alcohol use or dependence.
- •Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness.
- •Exclusion for Receipt of Antiretroviral Drugs in the BIA Arm
- •Note:A key component of this pilot study is to estimate the potential effect of ARVs during acute infection when applied on a large population scale.In effect, this pilot study should be viewed as a pilot for an effectiveness trial. Consequently, we will randomize all eligible participants to one of the three arms. If, however, persons should not receive ARVs for a variety of medically-related reasons, these persons will remain in the BIA arm, but will not receive ARVs. Women who are of reproductive potential but who refuse to use at least one form of contraception (see below), will remain in the BIA arm but will not receive ARVs. Similarly, persons randomized to the BI arm who do not attend all sessions will remain in the BI arm.
- •Persons randomized to BIA with any of the following conditions will be excluded from receiving ARVs, but will remain in the BIA group for purposes of analysis.
- •Laboratory values obtained at Day 0 prior to initiating ARVs at a subsequent visit
- •Absolute neutrophil count <300/mm3
- •Hemoglobin <8.0 g/dL
- •Platelet count <40,000/mm3
- •Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase > 5 x upper limit of normal (ULN)
- •Total bilirubin >2.5 x ULN
- •Creatinine Clearance (CrCl) <60 mL/min
- •Hepatitis B surface antigen positivity
- •Positive serum or urine pregnancy test at Day
- •Breastfeeding
- •Refusal to use at least one method of contraception, if a woman is of reproductive potential.
- •Acceptable forms of contraception include: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, intrauterine device (IUD), or a hormonal-based contraceptive.
- •Women not meeting the reproductive potential criteria above may receive the study drugs without using contraception.
- •Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
- •Requirement for any current medications that are prohibited with any study drugs.
研究组 & 干预措施
Standard Counseling Arm
The SC arm consists of a single session of standard HIV prevention messages during HIV post-test counseling. The counseling will be comparable to that given to persons with established HIV infection with supplemental information regarding the acute stage of their infection.
干预措施: Standard HIV prevention messages (Behavioral)
Behavioral Intervention Arm only
Behavior- BI: Information-Motivation-Behavioral Skills Model the Information-Motivation-Behavioral Skills (IMB) Model. The 5 sessions are designed to provide participants with the information, motivation, and skills needed to abstain or practice protected sex during the brief acute HIV period, as well as plan for long-term behavioral risk reduction.
干预措施: Standard HIV prevention messages (Behavioral)
Behavioral Intervention plus ARV
The BIA arm consists of the behavioral intervention plus antiretroviral drugs (ARVs) with raltegravir (400 mg twice daily) and fixed dose combination (FDC) emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (200/300 mg daily) orally for 12 weeks.
干预措施: Standard HIV prevention messages (Behavioral)
Behavioral Intervention plus ARV
The BIA arm consists of the behavioral intervention plus antiretroviral drugs (ARVs) with raltegravir (400 mg twice daily) and fixed dose combination (FDC) emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (200/300 mg daily) orally for 12 weeks.
干预措施: Raltegravir (Drug)
Behavioral Intervention plus ARV
The BIA arm consists of the behavioral intervention plus antiretroviral drugs (ARVs) with raltegravir (400 mg twice daily) and fixed dose combination (FDC) emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (200/300 mg daily) orally for 12 weeks.
干预措施: emtricitabine/tenofovir disoproxil fumarate (Drug)
结局指标
主要结局
Proportion of Persons Agreeing to be Screened for Acute HIV Infection Among Those Offered Screening
时间窗: 1 year
Prevalence of AHI Among Persons Screened
时间窗: 1 year
Prevalence of AHI among all persons screened. This measure is among all persons screened, prior to randomization.
Proportion of Persons With AHI Successfully Recruited Into the Study
时间窗: 1 year
This outcome reflects the ability to recruit persons with AHI into a study. The outcome is based on the population prior to randomization.
Proportion of Participants Completing Full Course of ARVs in Arm BIA
时间窗: 1 year
Proportion of participants in the BIA arm receiving full course of ARVs. This outcome is calculated among the BIA arm only, as that
Proportion of Participants in Arm BI and BIA (Combined) Who Complete the 4 Behavioral Sessions Within 3 Weeks of Enrollment.
时间窗: 1 year
In this pilot study, we addressed our ability to complete the behavioral intervention quickly. As two arms received the behavioral intervention, this outcome is combined across those two arms.
Proportion of Persons Completing All Scheduled Visits in Each Study Arm
时间窗: 1 year
Number of Adverse Events
时间窗: one year
Mean number of adverse events per group
次要结局
- Blood HIV RNA Concentration at Week 12(12 weeks)
- Blood HIV RNA Concentration at Week 26(26 weeks)
- Genital HIV RNA Concentration - Week 12, Men(12 weeks)
- Suppression of HIV RNA to <1000c/ml at 12 Weeks(12 weeks)
- Unprotected Sex Acts in Previous One Week - 12 Weeks(12 weeks)
- Unprotected Sex Acts in Previous One Week - 26 Weeks(26 weeks)
- Unprotected Sex Acts in Previous One Week - 52 Weeks(52 weeks)
- Unprotected Sex Acts in Previous One Month - 12 Weeks(12 weeks)
- Unprotected Sex Acts in Previous One Month - 26 Weeks(26 weeks)
- Unprotected Sex Acts in Previous One Month - 52 Weeks(52 weeks)
- Cumulative Incidence of Gonorrhea, Chlamydial Infection and Trichomoniasis (Composite)(52 weeks)
- Cumulative Incidence Herpes Simplex Virus Type 2(52 weeks)
- Number of Partners Reporting for HIV Testing(52 weeks)
- Proportion of Partners Reporting for HIV Testing(52 weeks)
- Time to HIV RNA Suppression <1000 c/ml(From date of randomization until viral load suppression, up to 52 weeks)
- Blood HIV RNA Concentration at Week 52(52 weeks)
- Genital HIV RNA Concentration - Week 12, Women(12 weeks)
- Genital HIV RNA Concentration - Week 26, Women(26 weeks)
- Genital HIV RNA Concentration - Week 52, Women(52 weeks)
- Genital HIV RNA Concentration - Week 26, Men(26 weeks)
- Genital HIV RNA Concentration - Week 52, Men(52 weeks)