title: Detection of Acute and Early HIV-1 Infections in an HIV Hyper-Endemic Area with Limited Resources.
abstract: BACKGROUND
  Two thirds of the world's new HIV infections are in sub-Saharan Africa. Acute HIV infection (AHI) is the time of virus acquisition until the appearance of HIV antibodies. Early HIV infection, which includes AHI, is the interval between virus acquisition and establishment of viral load set-point. This study aimed to detect acute and early HIV infections in a hyper-endemic setting.
  
  
  METHODS
  This was a cross-sectional diagnostic study that enrolled individuals who had negative rapid HIV results in five clinics in South Africa. Pooled nucleic acid amplification testing (NAAT) was performed, followed by individual sample testing in positive pools. NAAT-positive participants were recalled to the clinics for confirmatory testing and appropriate management. HIV antibody, p24 antigen, Western Blot and avidity tests were performed for characterization of NAAT-positive samples.
  
  
  RESULTS
  The study enrolled 6910 individuals with negative rapid HIV results. Median age was 27 years (interquartile range {IQR}: 23-31). NAAT was positive in 55 samples, resulting in 0.8% newly diagnosed HIV-infected individuals (95% confidence interval {CI}: 0.6-1.0). The negative predictive value for rapid HIV testing was 99.2% (95% CI: 99.0-99.4). Characterization of NAAT-positive samples revealed that 0.04% (95% CI: 0.000-0.001) had AHI, 0.3% (95% CI: 0.1-0.4) had early HIV infection, and 0.5% (95% CI: 0.5-0.7) had chronic HIV infection. Forty-seven (86%) of NAAT-positive participants returned for follow-up at a median of 4 weeks (IQR: 2-8). Follow-up rapid tests were positive in 96% of these participants.
  
  
  CONCLUSIONS
  NAAT demonstrated that a substantial number of HIV-infected individuals are misdiagnosed at South African points-of-care. Follow-up rapid tests done within a 4 week interval detected early and chronic HIV infections initially missed by rapid HIV testing. This may be a practical and affordable strategy for earlier detection of these infections in resource-constrained settings. Newer molecular tests that can be used at the points-of-care should be evaluated for routine diagnosis of HIV in hyper-endemic settings.
authors.affiliation: Department of Medical Virology, University of Pretoria, City of Tshwane, South Africa.|National Health Laboratory Service-Tshwane Academic Division (NHLS-TAD), City of Tshwane, South Africa.
authors.forename: Simnikiwe H
authors.initials: SH
authors.lastname: Mayaphi
authors.affiliation: Department of Medical Virology, University of Pretoria, City of Tshwane, South Africa.|Toga Laboratories, Johannesburg, South Africa.
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Martin
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.|Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.|Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.affiliation: Biostatistics unit, Medical Research Council, City of Tshwane, South Africa.
authors.forename: Steve A S
authors.initials: SA
authors.lastname: Olorunju
authors.affiliation: Department of Internal Medicine, University of Pretoria, City of Tshwane, South Africa.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Tintinger
authors.affiliation: Department of Internal Medicine, University of Pretoria, City of Tshwane, South Africa.
authors.forename: Anton C
authors.initials: AC
authors.lastname: Stoltz
mesh_terms: D000208:Acute Disease / Q000453:epidemiology; D000328:Adult; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D019353:Endemic Diseases; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D019562:Viral Load