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
  • 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
  • See footnotes (i-iv)

Starting treatment

Treatment of PHI is recommended for all PLWH(v). Several circumstances indicate immediate treatment initiation

Circumstances where immediate treatment initiation should be advised:

  • Acute symptomatic infection
  • Severe or prolonged symptoms
  • Neurological disease
  • Age ≥ 50 years
  • CD4 count < 350 cells/µL
  • Pregnancy

The recommendation is based on:

  • Improvement of clinical symptoms of PHI, when present, especially severe general symptoms and/or nerurological disease
  • Demonstrated 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. Since PrEP will increase the early diagnosis, it will be very important in order to decrease transmission to treat these persons as soon as possible
  • Reduced anxiety and facilitated disclosure to contacts The PLWH 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 treatment is started, it should be continued. A subsequent interruption is not recommended

Treatment selection

  • The PLWH 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. A genotypic test is recommended
  • Therapy may have to start before the results of resistance testing become available. In such cases, preference should be given to starting a PI/b or an INSTI with high genetic barrier (DTG or BIC), in order to increase the barrier to resistance of the overall regimen. A potential advantage for selecting DTG o BIC is the faster VL suppression. The benefit of combining PI/r with INSTI has not been shown. A combination of TDF or TAF, FTC, and either DRV/b, DTG or BIC, should therefore be considered, 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

Other considerations

  • All PLWH should undergo investigations to diagnose sexually transmitted infections (e.g. syphilis, gonorrhoea, chlamydia), HBV, HCV and HPV. See Assessment. Antibody seroconversion can be delayed and tests to identify the viral RNA are required in order to identify a recent HCV infection
  • All  women living with of reproductive age should have a pregnancy test
  • All PLWH 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. 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 PLWH. 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) NB: HIV-VL levels are usually > 10,000 copies/mL
    • Stage III: HIV-RNA, p24 Ag and anti-HIV antibody positive by immuno assay, no specific WB bands (average duration 3.2 days)
    • Stage IV: as Stage III but indeterminate WB pattern (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)
  3. Everyone 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
  4. Some centres may have access to sero-incidence markers (e.g., anti-body 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
  5. Potential disadvantage of treatment: firm, controlled evidence that treatment of PHI results in clinical benefit in the long-term (relative to starting therapy past the PHI stage) is currently lacking. A small subset of PLWH can spontaneously control the infection without treatment (elite controllers)

See online video lectures When to start ART-Part 1, When to start ART-Part 2, What ART to start-Part 1 and What ART to start-Part 2 from the EACS online course on Clinical Management of HIV