creation date: 2026-04-22 17:56
tags: Pathologies
Human Immunodeficiency Virus Infection
Background
Definitions
Infection with human immunodeficiency virus (HIV) was clinically described in 1985.
Early HIV infection refers to the approximately 6-month period following acquisition of HIV.
Acute HIV infection refers to symptomatic early infection.
Other terminology exist in the literature but early and acute are the commonly used terms in clinical care.
Pathogenesis
HIV is part of the Retroviridae family of the Lenivirus genus. There are two types, HIV-1 and HIV-2, which vary in their severity, transmissibility, and prognosis. The majority of cases are HIV-1.
HIV enters the host typically through the anogenital mucosa, binding to CD4 molecules of dendritic cells. Dendritic cells are found in the tonsillar and adenoidal tissue as well. Other target cells include macrophages and other CD4+ T-cells.
Within 2 days, virus spread to regional lymph nodes and in another 3 days, virus is disseminated to systemic circulation and organs. A cellular HIV reservoir is quickly established, which is estimated by HIV DNA levels in peripheral blood mononuclear cells.
HIV continues to target CD4 cells, depleting stores within mucosa. Systemic CD4 targeting results in continuous loss of cells, leading to immune suppression.
HIV-specific immunity occurs simultaneously with infection, predominantly with CD8+ which lowers plasma RNA levels and within six months, will bring RNA levels to a stabilized set point.
Eventually, untreated HIV progresses to advance disease if untreated, and if criteria is met, a diagnosis of AIDS.
Clinical Presentation
Signs & Symptoms
In some patients, early HIV infection will be asymptomatic.
Within 2-4 weeks (or longer in some cases), signs and symptoms may arise:
- Constitutional symptoms (fever, fatigue, myalgias)
- Adenopathy
- Nontender lemphadenopathy of axillary, cervical, occipital
- Oropharyngeal findings
- Sore throat, pharyngeal edema, hyperemia, tonsilitis
- Painful mucocutaneous ulceration: shallow, sharply demarcated ulcers with white bases and thin area of surrounding erythema
- Generalized rash (most commonly upper throax, collar region, face)
- GI symptoms
- Nausea, diarrhea, anorexia, weight loss
- Neurologic findings
- Headache, retroorbital pain exacerbated by eye movement
- Aseptic meningitis and/or self-limited encephalopathy (uncommon)
In patients receiving PrEP (cabotegravir), presentation may be different, wherein classic symptoms are absent.
History & Physical Exam
History:
- Complete review of system
- Opportunistic infections or HIV-associated sequelae
- Risk factors for HIV transmission (sexual contact and risky behaviour, drug use, blood transfusions)
- Sexual history (number of partners, sexual practices, barrier use and frequency, previous history of STI)
- Drug use history (including type, frequency, means of administration, source/sharing of equipment)
- Immunization history
In the case of suspected exposure, determine how long ago was high-risk exposure.
Diagnosis
Criteria
Diagnosis is made with clinical suspicion by:
- RT-PCR-based viral load test (detectable load is diagnostic)
- Antigen/antibody test (negative in early infection, positive in early or established)
Work-up
Additional evaluation following diagnosis
- Drug resistance testing
- Screening for coinfections and prior exposures
Differential
Other diagnoses include:
- Mononucleosis due to Epstein-Barr virus (EBV) or cytomegalovirus (CMV)
- Toxoplasmosis
- Rubella
- Syphilis
- Disseminated gonococcal infection
- Viral hepatitis
- Viral infection
Red Flags / Complications
The primary complication of HIV infection is progression to AIDS, at which the immune system cannot prevent infection and death due to opportunistic infection can occur.
Management
Pre-Exposure Prophylaxis
Pre-exposure prophylaxis (PrEP) is an antiretroviral used to reduce the risk of HIV transmission. Adherent treatment can reduce the risk by >99%.
Indications for PrEP are:
- Sexual risk (eg. partner has uncontrolled HIV, MSM/trans women engaging in sexual practices associated with HIV, heterosexual person with partners from regions with generalized epidemics)
- Concomitant syphilis, gonorrhea, or mpox (associated with higher risk of HIV)
- IV drug use if patient reports sharing needles or equipment
Note that while PrEP is not needed for persons engaging in low-risk behaviour, they may still request PrEP. In such case, PrEP is typically provided given patient understands risks and benefits.
HIV testing should be completed prior to initiating PrEP.
Prophylaxis consist of:
- Tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) PO - indicated for all cases
- Cabotegravir or lenacapavir; PO or IM (not studied for drug injection risk)
Post-Exposure Prophylaxis
For patients who are potentially exposed to HIV, post-exposure prophylaxis (PEP) can reduce the risk of acquiring infection. Exposure may occur from:
- Sexual contact
- Exposure to infected blood
- Exposure to blood-contaminated blood fluids
- Perinatal transmission
In cases of injury/needle-stick, appropriate wound care should be performed.
Indications for PEP are:
- Patients presenting within 72 hours of sexual or percutaneous exposure to source with HIV or unknown HIV status if exposure is high risk
- Health care providers presenting with 72 hours (and in some cases up to a week although with lower efficacy)
Regimens include (once daily):
- Bictegravir-emtricitabine-tenofovir alafenamide (single pill)
- Dolutegravir plus tenofovir disoproxil fumarate-emtricitabine (TDF-FTC)
- Dolutegravir plus tenofovir alafenamide-emtricitabine (TAF-FTC)
Treatment of Early and Acute Infection
The mainstay of early HIV infection is antiretroviral therapy. This should be started as soon as possible to reduce symptom presence and severity.
The choice of therapy should be informed by the result of drug resistance testing. The primary concern is integrase resistance.
In patients who have never received cabotegravir LA (for PrEP):
- Bictegravir-tenofovir alafenamide-emtricitabine
- Dolutegravir plus tenofovir and either emtricitabine or lamivudine
For patients who have received cabotegravir LA a boosted-protease inhibitor-containing regimen is preferred.
Treatment is continued indefinitely and viral RNA levels are monitored regularly to ensure viral suppresion.