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
- 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
- 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
- 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
- A small subset of persons can spontaneously control the infection without treatment (elite controllers)
- 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/