Initiation of Antiretroviral Therapy During Acute HIV-1 Infection Leads to a High Rate of Nonreactive HIV Serology

Clin Infect Dis. 2016 Aug 15;63(4):555-61. doi: 10.1093/cid/ciw365. Epub 2016 Jun 17.

Abstract

Background: Third- and fourth-generation immunoassays (IAs) are widely used in the diagnosis of human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) during acute HIV infection (AHI) may impact HIV-specific antibodies, with failure to develop antibody or seroreversion. We report on the ability of diagnostic tests to detect HIV-specific antibodies in Thai participants initiating ART during AHI.

Methods: Participants with detectable plasma HIV RNA but nonreactive HIV-specific immunoglobulin G, enrolled in an AHI study, were offered immediate initiation of ART. Participants were tested at initiation and at 12 and 24 weeks following treatment using standard second-, third-, and fourth-generation IAs and Western blot (WB).

Results: Participants (N = 234) initiating ART at a median of 19 days (range, 1-62 days) from HIV exposure demonstrated different frequencies of reactivity prior to and following 24 weeks of ART depending on the IA. Third-generation IA nonreactivity prior to ART was 48%, which decreased to 4% following ART (P < .001). Fourth-generation IA nonreactivity was 18% prior to ART and 17% following ART (P = .720). Negative WB results were observed in 89% and 12% of participants prior to and following 24 weeks of ART, respectively (P < .001). Seroreversion to nonreactivity during ART was observed to at least one of the tests in 20% of participants, with fourth-generation IA demonstrating the highest frequency (11%) of seroreversion.

Conclusions: HIV-specific antibodies may fail to develop and, when detected, may decline when ART is initiated during AHI. Although fourth-generation IA was the most sensitive at detecting AHI prior to ART, third-generation IA was the most sensitive during treatment.

Clinical trials registration: NCT00796146 and NCT00796263.

Keywords: Bangkok; HIV-1; acute HIV infection; immunoassay; seroreversion.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Cohort Studies
  • Diagnostic Tests, Routine
  • Female
  • HIV Antibodies / blood*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Seropositivity
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Homosexuality, Male
  • Humans
  • Immunoglobulin G / blood*
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Viral / blood
  • Sexual and Gender Minorities
  • Thailand
  • Young Adult

Substances

  • Anti-HIV Agents
  • HIV Antibodies
  • Immunoglobulin G
  • RNA, Viral

Associated data

  • ClinicalTrials.gov/NCT00796146
  • ClinicalTrials.gov/NCT00796263