2. Technical approaches to differentiate vaccine-induced responses from infection
The confounding effects of VISR on HIV diagnostics are due to the fact that these tests are based on detection of antibodies (Fig. 1). Although the fourth generation of diagnostic HIV tests includes detection of viral antigens, they continue to detect antibodies and, therefore, are unlikely to address VISR challenges [7] and [8].
One way to prevent the complications of VISR is to develop tests that detect non-vaccine antibody responses or viral components, such as proteins, RNA, or DNA and to promote their use in community settings. Several small companies are making good progress toward differential tests. One such example is HIV-Selectest [9], [10] and [11], which is being developed by Immunetics, Inc. HIV-Selectest detects antibodies to a region in gp41 that is rarely included in vaccine immunogens and can therefore be used for differential serologic testing. HIV-Selectest has been tested against specimens from a number of clinical trials with good results [11] and [12].
With regard to detecting viral components, monoclonal antibodies can be used to detect viral proteins, such as capsid protein (p24), in the blood, but tests based on this strategy must overcome the challenge of plasma antibodies competing with the assay antibody. Detection of HIV RNA by quantitative PCR is highly accurate and is used in management of HIV disease. However, this assay is complex, expensive, and may give false-negative results in individuals who naturally control viral load or are on ARV medications. Qualitative nucleic acid (DNA or RNA or both) assays face similar challenges, but may provide a cheaper and more reliable alternative. The only nucleic acid-based diagnostic test for HIV infection approved by the US Food and Drug Administration (FDA) is the Aptima HIV-1 RNA assay (Hologic), and there are few point-of-care nucleic acid-based diagnostic tests in development.
In addition to the challenge of technological feasibility, the tests must be adaptable to low-resource settings where electricity and cold chain are not always available. These technologies must also be portable, easy to use with little training, and inexpensive to operate. From a regulatory perspective, the FDA considers HIV tests as Class III devices (i.e., high-risk medical devices), which is the most stringent regulatory category [13]. Therefore the development of differential HIV tests capable of distinguishing VISR from HIV infection entails more regulatory and logistical complexities than other diagnostic areas, discouraging large diagnostic companies from investing in such specialized tests.
Licensure of an HIV vaccine would drastically increase the need for differential testing. However, in the absence of a widely available HIV vaccine, serological tests are likely to remain the primary diagnostic approach. Thus, it is highly unlikely that the challenges that trial participants with VISR face in the community will have simple/rapid technological solutions in the near future. Therefore, it is up to the organizations sponsoring these studies to help study participants avoid social harm by offering support and state-of-the art diagnostic testing.
2. เทคนิคยื่นเพื่อแบ่งแยกการตอบสนองที่เกิดจากวัคซีนจากเชื้อผล confounding ของ VISR การวินิจฉัยเชื้อเอชไอวีได้เนื่องจากข้อเท็จจริงที่ว่าการทดสอบเหล่านี้จะขึ้นอยู่กับตรวจแอนตี้ (Fig. 1) แม้ว่ารุ่นที่สี่ของเอชไอวีเทครวมถึงตรวจหาไวรัส antigens พวกเขายังคงตรวจพบแอนตี้ แล้ว ดังนั้น ไม่มีการท้าทาย VISR ที่อยู่ [7] [8]วิธีการป้องกันภาวะแทรกซ้อนของ VISR หนึ่งคือ พัฒนาทดสอบที่ตรวจหาแอนติบอดีวัคซีนไม่ตอบหรือคอมโพเนนต์ไวรัส เช่นโปรตีน อาร์เอ็นเอ หรือดีเอ็นเอ และ การส่งเสริมการใช้ในการตั้งค่าของชุมชน บริษัทขนาดเล็กหลายแห่งกำลังทำการทดสอบแตกต่างก้าวหน้าดี อย่างหนึ่งคือ เชื้อเอชไอวี-Selectest [9], [10] [11], และที่จะถูกพัฒนา โดย Immunetics, Inc. เอชไอวี-Selectest ตรวจพบแอนตี้กับภูมิภาคใน gp41 ที่แทบไม่มีอยู่ในวัคซีน immunogens และสามารถใช้สำหรับการทดสอบ serologic แตกต่างดังนั้น Selectest เอชไอวีได้ถูกทดสอบกับไว้เป็นตัวอย่างจากการทดลองทางคลินิกกับผลดี [11] [12]With regard to detecting viral components, monoclonal antibodies can be used to detect viral proteins, such as capsid protein (p24), in the blood, but tests based on this strategy must overcome the challenge of plasma antibodies competing with the assay antibody. Detection of HIV RNA by quantitative PCR is highly accurate and is used in management of HIV disease. However, this assay is complex, expensive, and may give false-negative results in individuals who naturally control viral load or are on ARV medications. Qualitative nucleic acid (DNA or RNA or both) assays face similar challenges, but may provide a cheaper and more reliable alternative. The only nucleic acid-based diagnostic test for HIV infection approved by the US Food and Drug Administration (FDA) is the Aptima HIV-1 RNA assay (Hologic), and there are few point-of-care nucleic acid-based diagnostic tests in development.In addition to the challenge of technological feasibility, the tests must be adaptable to low-resource settings where electricity and cold chain are not always available. These technologies must also be portable, easy to use with little training, and inexpensive to operate. From a regulatory perspective, the FDA considers HIV tests as Class III devices (i.e., high-risk medical devices), which is the most stringent regulatory category [13]. Therefore the development of differential HIV tests capable of distinguishing VISR from HIV infection entails more regulatory and logistical complexities than other diagnostic areas, discouraging large diagnostic companies from investing in such specialized tests.Licensure of an HIV vaccine would drastically increase the need for differential testing. However, in the absence of a widely available HIV vaccine, serological tests are likely to remain the primary diagnostic approach. Thus, it is highly unlikely that the challenges that trial participants with VISR face in the community will have simple/rapid technological solutions in the near future. Therefore, it is up to the organizations sponsoring these studies to help study participants avoid social harm by offering support and state-of-the art diagnostic testing.
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