Acute retroviral syndrome

Overview

Acute Retroviral Syndrome (ARS), also known as primary HIV infection or acute HIV syndrome, is the body’s initial response to infection with the human immunodeficiency virus (HIV). It typically occurs 2–4 weeks after exposure and represents the earliest stage of HIV infection. During ARS, the virus replicates rapidly and spreads throughout the body, causing a temporary drop in CD4+ T cells and a flu-like illness. This stage is highly infectious, and individuals may not yet know they are HIV-positive, making early detection critical for timely treatment and prevention of transmission.

Causes

Acute retroviral syndrome is caused by infection with HIV-1 (the most common strain) or less commonly HIV-2. The virus is transmitted through:

• Unprotected sexual contact (vaginal, anal, or oral)

• Sharing of needles or syringes

• Transfusion of contaminated blood (extremely rare in developed countries)

• Mother-to-child transmission during pregnancy, birth, or breastfeeding

Once HIV enters the body, it targets immune cells—primarily CD4+ T cells—leading to widespread infection and immune activation.

Symptoms

Symptoms of ARS typically appear within 2 to 4 weeks after HIV exposure and may last 1–3 weeks. Not all individuals experience symptoms, but when they do, they often resemble mononucleosis or flu. Common signs include:

• Fever

• Fatigue and malaise

• Swollen lymph nodes

• Sore throat

• Muscle and joint pain

• Skin rash: Often maculopapular and affects the trunk

• Headache

• Night sweats

• Diarrhea

• Mouth ulcers

Because these symptoms are non-specific, ARS can easily be mistaken for other viral illnesses.

Diagnosis

Diagnosing ARS is crucial but challenging due to its nonspecific symptoms. Standard HIV antibody tests may be negative during this early window period. Recommended diagnostic methods include:

• HIV RNA PCR (viral load test): Detects HIV RNA as early as 10 days post-infection

• HIV antigen/antibody combination test (4th generation): Detects both p24 antigen and antibodies; effective within 2–3 weeks of exposure

• CD4 count: May be temporarily low during acute infection

• HIV Western blot or confirmatory testing: To validate initial screening results

Clinicians should always take a detailed sexual and exposure history and consider ARS in patients with unexplained febrile illness and risk factors for HIV.

Treatment

The mainstay of treatment for ARS is the early initiation of antiretroviral therapy (ART). Starting ART during the acute phase has been shown to:

• Limit viral reservoir formation

• Preserve immune function

• Reduce the likelihood of transmission to others

• Improve long-term health outcomes

ART typically involves a combination of three drugs from at least two different classes, such as integrase inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs).

Additional management includes counseling, partner notification, and screening for other sexually transmitted infections (STIs).

Prognosis

With early diagnosis and consistent treatment, the long-term outlook for individuals with HIV is excellent. Those who begin ART during the acute phase may maintain a near-normal life expectancy and reduce their viral load to undetectable levels, thereby preventing onward transmission (“Undetectable = Untransmittable” or U=U).

Without treatment, however, HIV progresses through stages of chronic infection and eventually leads to AIDS. Early detection during the ARS phase provides a unique opportunity to intervene and drastically improve quality of life and health outcomes.