Empiric Therapy of Helminth Co-infection to Reduce HIV-1 Disease Progression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 948
- 试验地点
- 1
- 主要终点
- CD4 count
研究概览
简要总结
Abstract:
Over 25 million HIV-1 infected individuals are currently living in Africa and as many as 50-90% may be co-infected with soil transmitted helminths such as roundworms, hookworms or whipworms. Helminth infection in HIV-1-infected individuals may increase HIV-1 RNA levels and increase the rate of progression of HIV-1 to AIDS. Studies have also shown that successful treatment of helminth co-infection (as documented by clearance of helminth eggs in stool) led to a significant decrease in HIV-1 plasma viral load (-0.36 log10). This change in viral load was significantly greater than that seen in those individuals without documented clearance of their helminth co-infection (+0.67 log10) (p=0.04). Studies conducted in Africa have shown an estimated 2.5-fold increased risk for sexual transmission of the HIV-1 for each log increase in plasma HIV-1 viral load. In addition to direct effects on plasma viral load, the rate of CD4 cell decline in helminth infected individuals may be directly impacted by the significant immune activation seen with such co-infection.
The investigators propose a randomized controlled trial examining the potential benefits of routine empiric helminth eradication in HIV-1 infected adults who do not yet qualify for antiretroviral (ARV) therapy in Kenya. The current standard of care of symptomatic diagnosis and treatment will be compared to a systematic empiric scheduled de-worming program for HIV infected adults. The investigators will compare markers of disease progression including rate of CD4 decline and changes in HIV-1 RNA levels between the two treatment arms.
详细描述
INTRODUCTION AND BACKGROUND: BACKGROUND, SIGNIFICANCE AND RATIONALE
• Epidemiology of HIV-1 and helminth infections in Africa: Over two thirds of all HIV-1 infected individuals live in Africa. An expected 4 million new infections will occur this year in Africa alone. While antiretroviral therapies (ARTs) offer the hope of stemming this tremendous public health disaster, the reality is that many individuals are not able to access ARTs. In addition, millions of HIV infected individuals do not yet qualify for ART based on clinical or immunologic staging criteria. Alternative care strategies to delay immunosuppression and reduce infectivity are critically needed. Treatment of co-infections that are prevalent in areas of high HIV-1 sero-prevalence may be one strategy to address this need.
Helminths represent some of the most common infections of humans throughout the world. It is estimated that over half of all individuals living in Sub-Saharan Africa are infected with at least on species of soil transmitted helminths. Distribution mapping of HIV-1 sero-prevalence and helminth infection prevalence reveal remarkably geographic similarities.
We have recently conducted a large study of helminth infection among HIV-1 infected adults at several sites in Kenya. While rates of helminth co-infection are highest in Kilifi and Nyanza sites, there is a significant rate of co-infection even within the greater Nairobi area.
We also determined that while hookworm was the most common helminth identified in this cohort, the type of helminth infection varied significantly with the location.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must not be or have been on highly active antiretroviral therapy.
- •Participants must have CD4 count > 350 cells/mm3 in order to be enrolled in the randomized controlled trial.
- •Participants must be at least 18 years of age.
- •Participants must be able and willing to participate and give written informed consent.
- •Participants must be able and willing to return for the scheduled follow-up visits.
排除标准
- •Participants must not be pregnant at the time of enrollment (by urine HCG testing).
研究组 & 干预措施
1
Arm 1 will receive an intensive regimen of anti-helminthic therapy consisting of albendazole every three months for two years and praziquantel at enrollment and at one year of follow up.
干预措施: Albendazole (Drug)
1
Arm 1 will receive an intensive regimen of anti-helminthic therapy consisting of albendazole every three months for two years and praziquantel at enrollment and at one year of follow up.
干预措施: Praziquantel (Drug)
2
Arm 2 will receive symptomatic diagnosis and treatment of helminth infection as is current standard of care in Kenya.
干预措施: Current standard of care in Kenya (Drug)
结局指标
主要结局
CD4 count
时间窗: every 6 months for 24 months (enrollment and months 6, 12, 18, and 24 )
The primary measure of efficacy for the randomized clinical trial is the time to ART eligibility and the time to CD4 counts of less than 200 and 350 cells/mm3.
HIV-1 RNA level
时间窗: enrollment, 12, and 24 months.
次要结局
- Markers of clinical disease progression as measured by WHO staging criteria(Every 3 months for 24 months (enrollment, months 3, 6, 9, 12, 15, 18, 21, and 24))
研究者
Judd Walson
Principal Investigator
University of Washington