Detection of Acute and Early HIV-1 Infections in an HIV Hyper-Endemic Area with Limited Resources

PLoS One. 2016 Oct 20;11(10):e0164943. doi: 10.1371/journal.pone.0164943. eCollection 2016.

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.

MeSH terms

  • Acute Disease / epidemiology
  • Adult
  • CD4 Lymphocyte Count
  • Cross-Sectional Studies
  • Early Diagnosis
  • Endemic Diseases*
  • Female
  • HIV Infections / diagnosis*
  • HIV Infections / epidemiology*
  • HIV Infections / immunology
  • HIV-1 / physiology*
  • Humans
  • Male
  • Viral Load

Grants and funding

1. National Health Laboratory Service Research Trust (NHLS-RT) grant (www.nhls.ac.za), SHM and DJM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 2. Federation of Infectious Diseases Societies of Southern Africa and GlaxoSmithKline (FIDSSA-GSK) grant (www.fidssa.co.za), SHM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 3. University of Pretoria research assistant grant (www.up.ac.za), SHM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 4. South African Medical Research Council Self Initiated Research (MRC-SIR) grant (www.mrc.ac.za), SHM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 5. Discovery Foundation (www.tshikululu.org.za), SHM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 6. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (www.nih.gov), TCQ and OL; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. DJM is an employee of a commercial company, Toga Laboratories. The Toga Laboratories provided support in the form of salaries for [DJM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. SHM received a research grant from a commercial funder, GlaxoSmithKline. GlaxoSmithKline did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.