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Primary HIV Infection (PHI)

Definition of PHI

  • High-risk exposure within previous 6 weeks, and
  • Detectable virus in plasma (p24 Ag and/or HIV-RNA) and/or
  • Evolving anti-HIV antibody reactivity (negative or indeterminate to positive)
  • With or without clinical symptoms
  • In case of positive serology with complete seroconversion, a negative anti-HIV test within the last 6 months
  • See footnotes (i-iv)

Classification of PHI

  • Acute infection: HIV detection (p24 Ag and/or HIV-RNA) in the absence of HIV antibody
  • Recent infection: HIV antibody detection; up to 6 months after infection
  • Where available, Western Blot (WB) or Immunoblot patterns of reactivity can be used to stage the infection as follows:
    • Stage I: HIV-RNA positive only (average duration 5 days) HIV-VL levels are median 2,000 copies/mL (IQR 300-20,000 copies/mL), and are < 100 copies/mL in approximately 10% of cases. Low HIV-VL levels should be interpreted with caution due to the risk of false positivity
    • Stage II: HIV-RNA and p24 Ag positive only (average duration 5.3 days) HIV-VL levels are usually > 10,000 copies/mL
    • Stage III: HIV-RNA, p24 Ag and anti-HIV antibody positive by immune assay, no specific WB bands (average duration 3.2 days)
    • Stage IV: as Stage III but indeterminate WB pattern (average duration 5.6 days)
    • Stage V: as Stage III, but reactive WB pattern lacking p31 reactivity (average duration 69.5 days)
    • Stage VI: as stage III but full WB reactivity including a p31 band (indefinite)
  • Stages may be delayed in PrEP users with PHI
  • See footnotes (i-v)

Starting treatment

Treatment of PHI is recommended for all cases

The recommendation is based on:

  • Improvement of clinical symptoms of PHI, when present, especially severe general symptoms and/or neurological disease
  • Benefits of early therapy:
    • virological: decrease of the HIV-VL set-point and size of the viral reservoir; reduction of viral genetic evolution
    • immunological: decrease of immune activation and inflammation; preservation of immune function and integrity of lymphoid tissue; possibly neurological and gut protection; possibly enhancement of post-treatment control and response to future eradication strategies
  • Usually short interval between identification of PHI and a CD4 count < 500 cells/μL
  • Potential benefits of treatment for the community: reduced risk of transmission. Most infections are transmitted by persons who are unaware of their HIV status.
  • Reduced anxiety and facilitated disclosure to contacts The person should be counselled on indications and benefits of starting treatment as soon as possible, despite absence of demonstrated improved long-term clinical benefits(v)
  • Once ART is started, it should be continued. A subsequent interruption is not recommended

Treatment selection

  • The person should preferably be recruited into a clinical trial or studies investigating HIV curative strategies
  • Any use of PrEP or PEP should be identified and taken into account when choosing the initial regimen
  • A drug resistance test is recommended in all cases as soon as possible after diagnosis
  • Therapy may have to start before the results of resistance testing become available. In such cases, preference should be given to starting a three drug regimen including preferably a second generation INSTI with high barrier to resistance (DTG or BIC) or a PI/b, in order to increase the barrier to resistance of the overall regimen. More than three active drugs are not needed. 
    A potential advantage for selecting DTG or BIC is the faster VL suppres-sion. The benefit of combining PI/b with INSTI has not been shown. It is recommended to select a first-line regimen with a high barrier to resistance, preferably a second generation INSTI or alternatively a PI/b plus TDF or TAF and XTC, and the regimen adjusted, if needed, once the resistance test becomes available and viral load suppression is achieved. Where such a regimen is not available, national epidemiological data on prevalence and patterns of transmitted drug resistance (where available and sufficiently representative) may assist with the treatment selection process. A two drug regimen is not recommended. 
  • In cases of injectable PrEP with LA CAB, a DRV/b regimen should be immediately started until resistance test is available.

Other considerations

  • All people with recent HIV acquisition should undergo investigations to diagnose sexually transmitted infections (e.g. syphilis, gonorrhoea, chlamydia), HBV, HCV and HPV. See Assessment. Antibody seroconversion for hepatitis C can be delayed and tests to identify the viral RNA are required in order to identify a recent HCV infection
  • All women living with HIV of reproductive age should have a pregnancy test
  • All persons should be counselled about the high risk of transmission, preventive measures, and importance of notifying partners

Footnotes

  1. HIV-1 RNA becomes detectable in plasma around day 11 after exposure, approximately 7 days before p24 Ag and 12 days before anti-HIV antibodies
  2. Every person with detectable HIV-VL and negative or indeterminate serology must receive confirmation of anti-HIV antibody seroconversion in follow-up testing. The interval of testing (up to stage V) is one week
  3. Some centres may have access to sero-incidence markers (e.g., antibody avidity testing) that identify an infection acquired within the previous 3-6 months. Assay reliability varies and results should be interpreted with caution when they are the sole indicators of a recent infection
  4. A small subset of persons can spontaneously control the infection without treatment (elite controllers)
  5. Post-treatment controllers. A small proportion of recently-infected persons have been able to spontaneously control HIV-infection following ART discontinuation, when ART was initiated during PHI


See online lectures for ART from the EACS online course 
https://www.eacsociety.org/education/online-course/