This post is a part II to September 14th morning report to go over an approach to new diagnosis of HIV.

1. Timecourse of Infection

You might be familiar with the following diagram which outlines that in the first 3-9 weeks of acute HIV infection, patients may develop acute retroviral syndrome with flu-like symptoms such as pharyngitis, fever, lymphadenopathy, rash, arthralgia, myalgia. Thereafter, there may be a period of time with clinical latency and if untreated, over a period of several years the CD4 can decrease while HIV RNA viral load increases and in this setting opportunistic infections can be seen.

2. New Diagnosis of HIV

There is lots of material to cover when it comes to counselling, vaccinations, investigations, medications, and referrals so this lecture is not inclusive of everything you need to know. In the next two sections I included a couple of pearls on tests you would want to send if you have a new diagnosis of HIV.

• General: CBC, lytes, Cr, LFTs, CK, amylase, LDH, lipid profile, glucose, CXR, urinalysis
• G6PD testing if dapsone to be used
• Beta-HCG if child-bearing potential
• HIV specific
  • Make sure you document a +HIV test
  • Current CD4 count, viral load
  • Genotyping
  • HLA-B5701 for abacavir hypersensitivity +/- CCR5 tropism if maraviroc to be used
  • Other infections:
    • Hepatitis A IgM antibody, Hep B surface Ag, Hep B surface Ab, Hep B core Ab, Hep C antibody
    • Syphilis serology
    • Toxoplasma IgG
    • Cryptococcal Ag
    • TB skin test
    • Gonococcal chlamydia urine/rectal/anal/pharyngeal
    • PAP smear

3. When to initiate therapy?

The following table is from the new JAMA guidelines which state that anti-retroviral therapy should be started right away after HIV diagnosis if patient is ready to commit to treatment. Initiation of anti-retroviral therapy is recommended within 2 weeks of initiation of treatment for most opportunistic infections EXCEPT for individuals with TB and CD4 cell counts of 50/uL or above, then you initiate within 2-8 weeks of initiation of TB treatment. For individuals with cryptococcal meningitis, ART should be initiated within 4-6 weeks after starting antifungal therapy.

4. Classes of Medications

There are many different classes of anti-retroviral drugs. Most regimens involved three drugs – two drugs make up the backbone (usually two nucleoside reverse-transcriptase inhibitors or NRTIs) and then one active drug such as a protease or integrase inhibitor. Usually anti-retroviral therapy involves a three-drug regimen but this can be combined in a single pill combination. See the pathophysiology and mechanism of action of the medications below which help remember how they act in the viral reverse transcriptase and integration pathway.

5. Opportunistic Infections

Finally, we ended our discussion on opportunistic infections (OIs) in the setting of chronic HIV infection and the following table demonstrates the CD4 count at which specific OI’s may be seen.

CD4 count < 500 cells/mm^3	Often asymptomatic Constitutional symptoms fever, night sweats, fatigue, weight loss Mucocutaneous lesions: HSV, VZV, oral hairy leukoplakia (EBV), candidiasis, Kaposi’s sarcoma (KS) Recurrent bacterial infections such as pneumonia Pulmonary and extrapulmonary TB Lymphoma
CD4 count < 200 cells/mm^3	Pneumocystis jiroveci pneumonia (PJP) Kaposi’s sarcoma Oral thrush Local and or disseminated fungal infections (Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum)
CD4 count < 100 cells/mm^3	Progressive multifocal leukoencephalopathy (PML) – JC virus Central nervous system toxoplasmosis
CD4 count < 50 cells/mm^3	CMV infections (reintis, colitis) Mycobacterium avium complex (MAC) Bacillary angiomatosis (disseminated Bartonella) Primary central nervous system lymphoma (PCNSL)

Prophylaxis for PJP is Septra TMP/SMX 1 double strength tab po daily (this also serves as toxoplasma prophylaxis). Azithromycin 1200 mg weekly is used for MAC however is initiated less frequently especially if patients are started immediately on anti-retroviral therapy and CD4 recovery is expected.

6. References

• https://i-base.info/guides/testing/timeline-for-immune-responses-and-testing
• 2020 HIV Guidelines: https://jamanetwork-com.myaccess.library.utoronto.ca/journals/jama/fullarticle/2771873
• HIV Info website: https://hivinfo.nih.gov/home-page 
• https://clinicalinfo.hiv.gov/en/guidelines/perinatal/table-4-what-start-initial-combination-regimens-antiretroviral-naive-pregnant
• Opportunistic infections: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultOITablesOnly.pdf

As always please don’t hesitate to reach out if any questions or comments at cmr@wchospital.ca