Early HIV Infection

Background

Acute HIV infection refers to the very early stages of HIV infection, or the interval from initial infection to the time that antibody to HIV is detectable; early HIV infection usually includes the first 6 months of infection. During the acute stage of HIV infection, patients typically have symptoms of acute retroviral illness, very high HIV RNA levels (>100,000 copies/mL) and detectable p24 antigen, and negative or indeterminate HIV antibody test results.

Diagnosing patients with acute HIV infection is a clinical challenge. The symptoms of acute HIV are nonspecific, and although many patients seek medical care for symptoms of acute retroviral syndrome, the diagnosis commonly is missed at initial presentation. The difficulties involve recognizing the clinical presentation of acute HIV infection and testing patients appropriately. In HIV treatment facilities, clinicians generally do not see patients with primary HIV infection unless they are referred with the diagnosis already established. In other health care settings, clinicians may not be familiar with the signs and symptoms of acute HIV infection and often do not consider this diagnosis. Despite the difficulties, recognizing early HIV infection in symptomatic patients is essential. Early diagnosis provides an opportunity for early linkage to HIV care and treatment and may decrease future HIV transmission by newly identified patients, who are particularly infectious during early untreated HIV infection.

After infection with HIV, it takes a median of about 25 days before the HIV antibodies are detectable in most people; in some individuals, it may be several months before seroconversion occurs. HIV RNA may be detectable within 10 days of infection and p24 antigen in about 15-20 days. Persons with known exposures to HIV, whether occupational or not, should be monitored closely beginning at about 3 weeks after exposure (routine monitoring at 6 weeks, 3 months, and 6 months after exposure to HIV is likely to result in delayed diagnosis of HIV infection). For information on postexposure prophylaxis, see chapters Nonoccupational Postexposure Prophylaxis and Occupational Postexposure Prophylaxis.

S: Subjective

Approximately two thirds of patients infected with HIV develop symptoms of acute HIV infection, a condition known as acute retroviral syndrome. Symptoms typically appear 2-6 weeks after exposure to HIV and generally include several of the following:

  • Fever (present in 80-90%)
  • Rash, often erythematous and maculopapular
  • Fatigue
  • Pharyngitis (with or without exudate)
  • Generalized lymphadenopathy
  • Urticaria
  • Myalgia/arthralgia
  • Anorexia
  • Mucocutaneous ulceration
  • Headache, retroorbital pain
  • Neurologic symptoms (e.g., aseptic meningitis, radiculitis, myelitis, cranial nerve palsies)

This symptomatic phase usually persists for 2-4 weeks or less, although lymphadenopathy may last longer. Symptoms and signs are similar to those of many other illnesses, including other viral syndromes, influenza, and mononucleosis. However, generalized lymphadenopathy, rash, thrush, and mucosal ulceration are sufficiently uncommon in most adult febrile illnesses that, when present, they should trigger suspicion of acute HIV infection. It is important to obtain a history of recent risk behaviors from all patients who present with symptoms consistent with acute HIV infection and to have a low threshold for testing for acute HIV infection. Common laboratory findings include leukopenia, thrombocytopenia, and mild transaminase elevations.

O: Objective

The 3rd-generation assays may detect HIV infection within 4 weeks, but new 4th-generation HIV antigen/antibody tests usually show positive results within 2-3 weeks after an infection occurs. During the symptomatic phase of HIV seroconversion, HIV antibody tests may still indicate negative or indeterminate serostatus. For patients who have negative or indeterminate antibody results but symptoms consistent with seroconversion illness and a recent risk history for HIV exposure, an HIV RNA (viral load) test should be performed. Patients with negative or indeterminate antibody test results but detectable HIV viral loads (particularly >10,000 copies/mL) can be considered to be infected with HIV, although the antibody test should be repeated later to confirm seroconversion. A low viral load (<10,000 copies/mL) may indicate a false-positive result, because viral loads typically run very high (i.e., >100,000 copies/mL and, often, millions of copies/mL) during the acute infection stage. For patients who have negative or indeterminate HIV antibody test results and low positive HIV viral loads, the HIV RNA test should be repeated on a different blood specimen.

The 4th-generation HIV tests do not distinguish between antigen positivity and antibody positivity. Patients with a positive result should be retested with an antibody test; if the result is negative or indeterminate and acute HIV is suspected, an HIV RNA test should be sent, as above (see chapter Expedited HIV Testing).

A/P: Assessment/Plan

Patients with early HIV infection will need additional medical evaluation, baseline laboratory testing, and intensive support, counseling, and education about HIV infection. See chapters Initial History, Initial Physical Examination, and Initial and Interim Laboratory and Other Tests for detailed information on the initial evaluation of HIV-infected patients.

Laboratory

The initial laboratory work should include the following:

  • CD4 cell count and HIV viral load.
  • A baseline HIV genotype test for all patients with early HIV infection, even those who do not choose to start antiretroviral treatment (ART). In some cities in the United States and Europe, 6-16% of infected individuals have acquired HIV virus strains with mutations that confer resistance to antiretroviral medications. These resistance mutations may be identified by early resistance testing, but may not be detectable later. (See chapter Resistance Testing.)
  • Patients diagnosed on the basis of HIV RNA should have an HIV antibody test repeated in 3-6 months to document seroconversion.

Treatment

ART is recommended for all persons with HIV, including those with early HIV infection. Some limited evidence suggests that treatment initiated during primary HIV infection may have particular benefits, including preserving HIV-specific immune function that would otherwise be lost as the infection progresses, limiting the size of the HIV viral reservoir, and decreasing the loss of gastrointestinal lymphoid tissue. In addition, early treatment is expected to decrease rates of HIV transmission during a time of heightened infectiousness.

The potential advantages of ART for primary infection must be weighed against the possibility of short- and long-term toxicities, the possibility of developing drug resistance, and the adherence challenges associated with starting ART quickly for newly diagnosed patients. Issues concerning the possible treatment of primary HIV infection are reviewed in the U.S. Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.

For pregnant women with acute or recent HIV, the risk of perinatal HIV transmission is very high; thus, ART should be started as early as possible to try to prevent infection of the infant (see chapter Reducing Perinatal HIV Transmission).

For patients who opt to start therapy during primary HIV infection, the choice of agents and the recommendations for monitoring are the same as those for the treatment of patients with chronic HIV infection (see chapter Antiretroviral Therapy). The initial goal of therapy in primary HIV infection is to suppress the HIV viral load to undetectable levels.

Patient Education

  • Patients with early HIV infection need support and counseling, as do all newly diagnosed patients.
  • Intensive education about HIV infection, the course of disease progression, prognosis, and the benefits and risks of ART must be undertaken.
  • Counseling patients about safer sex and drug injection techniques, as indicated, is especially important because these patients may have ongoing high-risk behaviors for HIV transmission and because they may be highly infectious during the primary infection period. (See chapter Preventing HIV Transmission/Prevention with Positives for more information about patient support and counseling in these areas.)

References

  • Grijsen ML, Steingrover R, Wit FW, et al.; Primo-SHM Study Group. No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial. PLoS Med. 2012;9(3):e1001196.
  • Hogan CM, Degruttola V, Sun X, et al.; A5217 Study Team. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals. J Infect Dis. 2012 Jan 1;205(1):87-96.
  • Kassutto S, Rosenberg ES. Primary HIV type 1 infection. Clin Infect Dis. 2004 May 15;38(10):1447-53.
  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed December 1, 2013.
  • Pilcher CD, Tien HC, Eron JJ Jr, et al.; Quest Study; Duke-UNC-Emory Acute HIV Consortium. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004 May 15;189(10):1785-92.
  • Schacker T, Collier AC, Hughes J, et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med. 1996 Aug 15;125(4):257-64.

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Abbreviations for Dosing Terminology

BID
twice daily
BIW
twice weekly
IM
intramuscular (injection), intramuscularly
IV
intravenous (injection), intravenously
PO
oral, orally
Q2H, Q4H, etc.
every 2 hours, every 4 hours, etc.
QAM
every morning
QD
once daily
QH
every hour
QHS
every night at bedtime
QID
four times daily
QOD
every other day
QPM
every evening
TID
three times daily
TIW
three times weekly