A Novel Method to Determine HIV Incidence Among Youth
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      Identifying young people with early HIV-1 infection is important for increasing linkage to
      care, for behavioral counseling, and for enrolling individuals into programs that can provide
      effective interventions to disease progression and improve outcome. This study will develop
      and evaluate a saliva-based sensitive/less sensitive (S/LS) assay for differentiating persons
      with recent HIV-1 infection (less than 133 days) from those with established HIV-1 infection.
    

Detailed description: 
      HIV infection incidence estimates are important, not only for determining specific
      populations where community HIV education sessions can have the most benefit or where changes
      in infection patterns are occurring, but also to target these populations for therapeutic
      interventions and measure their effect in the community. It is estimated that half of all new
      HIV infections in the United States occur in persons under the age of 25 each year,
      translating to approximately 20,000 new HIV-infected young people annually.

      Incidence can be estimated by testing a cohort of individuals for antibody at two different
      time periods and observing the number of new infections, or by demonstrating the presence of
      HIV p24 or viral RNA in antibody-negative persons. Since these strategies are logistically
      difficult, expensive, and/or require significant laboratory infrastructure, new
      laboratory-based strategies were devised that can classify individuals as recently infected
      or with established infection. These serologic assays are known as "sensitive/less sensitive
      (S/LS) assays". They are based on either the concept of antibody titer or the concept of
      antibody avidity. There are several S/LS tests available but all of them are performed on
      serum collected via venipuncture. Based on several studies showing that obtaining saliva is a
      more desirable method of collection for adolescents receiving HIV testing, it is anticipated
      that the collection of saliva and its use for determining HIV incidence by S/LS methods among
      adolescents would be a valuable adjunct for population studies and for increasing compliance
      for testing and enrollment.

      The aim of this study is to prove equivalence between the serum S/LS reference method (CDC
      validated serum S/LS Dilutional Vironostika (DV) from Organon Teknika) and the experimental
      method that uses an FDA approved saliva collection device (OraSure Technologies). Our
      rationale follows a syllogism, i.e., if the serum S/LS EIA (DV) is the best serologic method
      to determine incidence estimates and a saliva S/LS method is found to perform equivalently,
      then it follows that the saliva S/LS method can be used effectively to determine incidence.
      Therefore, our purpose is to show equivalence between the two assays. To address the issue of
      accuracy, further studies are planned to assess the saliva S/LS test against seroconversion
      panels where the exact time of acquisition of HIV infection is known.

      This is a cross-sectional, laboratory-based study designed to develop and evaluate a
      saliva-based S/LS assay for differentiating individuals with recent HIV infection (less than
      133 days) from those with established HIV infection. A total of 440 subjects will be
      recruited in the study. A serum and two saliva samples will be obtained from every subject.
      The first 40 patient samples will be used to develop and calibrate the saliva-based S/LS
      method. The remaining patient samples will be tested using the calibrated saliva based S/LS
      assay and the reference serum S/LS assay and concordance between the two methods will be
      analyzed.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Two hundred fifty subjects will be recruited from the fifteen sites of the Adolescent
        Trials Network for HIV/AIDS Interventions (ATN) and 190 from the BCHD STD Clinic, a
        sexually transmitted disease clinic of the Baltimore City Health Department (BCHD). The age
        range for subjects from the ATN clinical sites will be 12 through 24 years and those from
        the BCHD STD Clinic will be 17 through 30 years.
      
Biospecimen description: 
      Phenotypic and genotypic testing for antiretroviral drug (ART) resistance will be done on
      stored samples from all subjects who are identified as recently infected by the serum based
      DV S/LS reference method. An assay for viral replication fitness will also be done on these
      same samples. This testing will provide a recent assessment of prevalence of transmitted ART
      resistant HIV-1 in this population.
    
Keywords: HIV; Detuned Assay; Enzyme Immunoassay (EIA); HIV Incidence; Laboratory assay; Sensitive/Less sensitive Assay; Acute Infection