跳至主要内容
临床试验/NCT06363500
NCT06363500已完成不适用

Characterization of HIV-1 Reservoirs in HIV+ Adolescents

Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS1 个研究点 分布在 1 个国家目标入组 140 人开始时间: 2021年11月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
140
试验地点
1
主要终点
Archived HIV drug resistance mutations

研究概览

简要总结

Background: Combination antiretroviral therapy (cART) can bring HIV-1 in blood plasma to level undetectable by standard tests and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, cART is not curative, as within a few weeks of treatment cessation, HIV viremia in most patients rebounds except for rare elite or post-treatment controllers of viremia. The primary source of this rebound is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses integrated into the genomic DNA of resting memory CD4+ T cells. To achieve a cure for HIV, understanding the cell reservoir environment is of paramount importance. The size and nature of viral reservoir might vary per timing of therapy, therapeutic response, ART duration, and immune response. Mechanisms of reservoir maintenance generally depend on levels/type of immune recognition, dynamics of viral persistence are different between pediatric and adult populations, owing to, but not limited to, types/numbers of target cells, efficiency in clearing HIV-infected cells, plasma viremia and HIV drug resistance patterns. This difference could become more evident as these children grow toward adolescence (increasing population due to ART benefits), a stage during which suboptimal adherence is frequent, leading to viral rebound and archiving of resistant patterns.

Objectives: We plan to conduct a cross sectional study with the aim to characterize HIV reservoirs and their variability according to virological and immunological profiles of non-B HIV-1 vertically infected adolescents receiving antiretroviral therapy. Specifically, we shall (1) evaluate the size of HIV reservoir; (2) Determine HIV-1 genetic variability and drug resistance in cellular reservoirs; (3) Characterize immune activation/inflammation of HIV infected adolescents.

Methods: We plan to conduct an observational and comparative study involving 90 HIV-1 non-B infected adolescents aged 10-19 years vertically infected, have been on ART for at least 12 months selected from a cohort of the ongoing EDCTP-READY study; intravenous blood will be collected for CD4/CD8 count, plasmatic viral load, PBMCs isolation, immune activation/inflammatory markers, genotyping and Viral reservoir quantification. We will as well recruit a group of 30 HIV-negative adolescents as control for immunological profiling.

Overall impact: Our findings will help in advancing knowledge on HIV reservoir, in terms of size and genetic variability in adolescents living with HIV (ADLHIV). Such evidence will also help in understanding the effects of ART timing and duration on the size of reservoirs among ADLHIV, a unique population from whom findings generated will largely contribute in designing functional cure strategies in this vulnerable population.

详细描述

Title: Characterization of Viral Reservoirs among HIV-1 non-B Vertically Infected Adolescents receiving Antiretroviral Therapy in Cameroon.

Acronym: AVIR-study, Adolescent viral reservoir

Importance and relevance Sub-Saharan Africa (SSA) is disproportionally affected with HIV/AIDS, with close to 70% of the global epidemics. With the highest burden of paediatric HIV infections, about nine out of every 10 children living with HIV found in the SSA region(1, 2). Adolescents and young people represent a growing share of people living with HIV worldwide. In 2019, about 1.7 million [1.1 million-2.4 million] adolescents between the ages of 10 and 19 were living with HIV worldwide representing about 5% of all people living with HIV, about 1.5 million [1.0 - 2.1 million] or 88% of HIV infected adolescent live in SSA. In 2019 alone, 460,000 [260,000-680,000] young people between the ages of 10 to 24 were newly infected with HIV, of whom 170,000 [53,000-340,000] were adolescents between the ages of 10 and 19. To compound this, most recent data indicate that only 27% of adolescent girls and 16% of adolescent boys aged 15-19 in Eastern and Southern Africa - the region most affected by HIV - have been tested for HIV in the past 12 months and received the result of the last test. The testing rates in West and Central Africa and South Asia are even lower. If current trends continue, hundreds of thousands more will become HIV-positive in the coming years, and without knowing their status, adolescents will miss out on life-saving treatment. Additionally, a large population of children infected with HIV perinatally over the last decade are growing into adolescence (3). Of the estimated 690,000 people who died of AIDS-related illnesses in 2019, 110,000 (or approximately 16%) of them were children under 20 years of age. (UNICEF global and regional trends, July 2020).

With the advent and scalability of Antiretroviral therapy (ART), there is a global decrease in AIDS-related deaths. As of the end of 2019, 25.4 million people were accessing antiretroviral therapy, representing 67% of all people living with HIV. However, only 53% of children living with HIV were receiving ART. Interestingly, about 94% of all children receiving ART are from SSA (4). In this context of continuous new HIV paediatric infections and increasing coverage in paediatric ART, the number of children living with HIV will increase, suggesting a higher likelihood of reaching adolescent age and even adulthood if treatment regimens remain fully effective in controlling HIV infection (3, 4). ADLHIV therefore constitutes an HIV population with growing health concerns and with very limited findings for generalizable best practices specific to this target population, especially in SSA.

Like several West and Central African countries, Cameroon is still faced with a generalized HIV epidemiology (2.7% prevalence) (5), with higher prevalence among pregnant women (5.7%) and HIV-exposed infants/children (5.8% [958/16,638] positivity at first PCR and 15% at the end of the PMTCT cascade) (6). As of June 2018, the national coverage of ART was 51.5% (281,083), which includes 12,362 children below 15 years of age (6). Regarding response to ART in Cameroon, we reported an overall rate of 79.4% viral suppression, with significant disparities across age ranges: 81.1% in adults, 75.6% in children, and only 53.3% in adolescent aged 10-19 years (7). Similar to UNAIDS reports, adolescents living with HIV (ADLHIV) represent the most vulnerable and underserved population in response to the epidemics(1, 5). For a safer growth toward adulthood, there is need to prioritize this population for the quest of innovative treatment strategies that ensure their well-being and their contribution for the development of SSA.

研究设计

研究类型
Observational
观察模型
Other
时间视角
Cross Sectional

入排标准

年龄范围
10 Years 至 19 Years(Child, Adult)
性别
All
接受健康志愿者

入选标准

  • Consenting HIV+ Adolescents on ART

排除标准

  • Insufficient blood for lab tests

结局指标

主要结局

Archived HIV drug resistance mutations

时间窗: 6 months

Identify HIV drug resistance mutations in pro-viral HIV DNA

次要结局

  • HIV-1 reservoirs measurement(1 year)

研究者

发起方
Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS
申办方类型
Other Gov
责任方
Principal Investigator
主要研究者

Judith Ndongo Embola Torimiro

Researcher

Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS

研究点 (1)

Loading locations...

相似试验

Characterization of HIV-1 Reservoirs in HIV-1 Non-B... | 临床试验