Primary HIV Infection

Background

Primary 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. During this stage of HIV infection, patients typically have symptoms of acute HIV seroconversion illness, very high HIV RNA levels (>100,000 copies/mL), and negative or indeterminate HIV antibody test results.

Diagnosing patients with primary HIV infection is a clinical challenge. The symptoms of primary HIV are nonspecific, and although many patients seek medical care for symptoms of HIV seroconversion illness, 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 primary HIV infection in symptomatic patients is essential. Early diagnosis provides an opportunity for early linkage to HIV care 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 25 days before the HIV antibody test indicates positive results; in some individuals, it may be several months before seroconversion occurs. 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

HIV antibody tests usually show positive results within 4 weeks after an infection occurs. However, during the symptomatic phase of HIV seroconversion, these HIV antibody tests may still indicate negative or indeterminate serostatus. For patients who have symptoms consistent with seroconversion illness and a recent risk history for HIV exposure, an HIV RNA (viral load) test should be performed, in addition to the HIV antibody test, as part of the evaluation. Patients with negative antibody test results but high HIV viral loads (>100,000 copies/mL) can be considered to be infected with HIV, although the antibody test should be repeated later to confirm seroconversion. False-positive HIV viral loads have been reported in approximately 5% of cases involving patients who were tested after HIV exposures. A low viral load (<1,000 copies/mL) usually indicates a false-positive result at this stage, because viral loads typically run very high (i.e., >100,000 copies/mL and, often, millions of copies/mL) during the acute infection stage. Patients who have indeterminate HIV antibody test results, low HIV viral loads, and no clear HIV risk factors or symptoms of primary HIV infection should undergo repeat antibody testing in 4-6 weeks, without other interventions. For patients without significant risk factors, indeterminate antibody results rarely indicate evolving seroconversion.

A/P: Assessment/Plan

Patients with primary 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 primary 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 4-6 weeks to confirm seroconversion and HIV infection.

Treatment

It is reasonable to consider starting ART for patients with acute HIV infection, because some limited evidence suggests that treatment initiated during primary HIV infection may preserve HIV-specific immune function that would otherwise be lost as the infection progresses. However, it is not clear whether initiating early treatment yields long-term immunologic, virologic, or clinical benefits. 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. These issues are complex, and consultation with an HIV expert or referral to a clinical trial is recommended. 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 primary 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 risks and benefits 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

• Kassutto S, Rosenberg ES. Primary HIV type 1 infection. Clin Infect Dis. 2004 May 15;38(10):1447-53.
• 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.
• U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. March 27, 2012.
• Zetola NM, Pilcher CD. Diagnosis and management of acute HIV infection. Infect Dis Clin North Am. 2007 Mar;21(1):19-48, vii.