Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 1: Testing and Assessment

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 of >100,000 copies/mL, and negative or indeterminate HIV antibody tests.

The diagnosis of 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 clinics, clinicians generally do not see patients with primary HIV infection, unless they are referred with this 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.

After infection with HIV, it takes a median of 25 days before the HIV antibody test becomes positive; in some individuals, it may be several months before seroconversion. Individuals 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

More than three quarters of patients who become infected with HIV develop symptoms consistent with primary HIV infection. Symptoms typically appear a few days to a few weeks after exposure to HIV, and generally include several of the following:

• Fever
• Rash, often erythematous maculopapular
• Fatigue
• Pharyngitis
• Generalized lymphadenopathy
• Urticaria
• Myalgia/arthralgia
• Anorexia
• Mucocutaneous ulceration
• Headache, retroorbital pain
• Neurologic symptoms (eg, aseptic meningitis, radiculitis, myelitis)

This symptomatic phase usually persists for 2-4 weeks or less, although lymphadenopathy may last longer. These symptoms and signs are similar to those of many other illnesses, including other viral syndromes. To diagnose early HIV infection, clinicians must consider HIV in the differential diagnosis for at-risk patients with symptoms resembling flu or mononucleosis. A history of recent risk behaviors should be obtained from all patients who present with symptoms consistent with acute HIV infection.

O: Objective

During the symptomatic phase of HIV seroconversion, the HIV antibody test is likely to be negative or indeterminate. For patients who have symptoms consistent with seroconversion illness and a recent high-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 tests 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 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 (ie, >100,000 copies/mL and often millions of copies/mL) in acute infection. 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 have repeat antibody testing in 4-6 weeks, without other interventions. For patients without significant risk factors, indeterminate results rarely indicate evolving seroconversion.

A: Assessment and 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:

• The CD4 count and HIV viral load should be checked on 2 occasions within several weeks.
• A baseline HIV genotype test should be obtained 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, up to 15-20% of individuals infected in recent years have acquired HIV virus strains with mutations that confer resistance to antiretroviral medications. These resistance mutations may be identified by early resistance testing, but later may not be detectable. (See chapter Resistance Testing.)
• The HIV antibody test should be repeated in 4-6 weeks to document the HIV status of patients who are presumed to have primary HIV infection.

Treatment

It is reasonable to consider starting combination ART in 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 yet 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 antiretrovirals quickly in newly diagnosed patients. These issues are complex, and consultation with an HIV expert or referral to a clinical trial is recommended.

For patients who choose to start therapy during primary HIV infection, the choice of agents and the monitoring of patients on treatment are similar to those in the treatment of 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.

Clinical trials across the country currently are recruiting individuals to evaluate both the natural history of primary HIV infection and the possible benefits of treatment of acute HIV infection. Information on clinical studies of primary HIV may be obtained through the AIDS Clinical Trials Information Service (ACTIS) on its Web site at http://www.aidsinfo.nih.gov/clinicaltrials or by telephone at 800-HIV-0440. Issues concerning the possible treatment of primary HIV infection also 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.

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, prognosis, and the risks and benefits of ART must be undertaken. Counseling about safer sex and drug injection techniques, as indicated, is especially important for these patients because they 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

• Daar ES, Little, S, et al. Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network. Ann Intern Med. 2001 Jan 2;134(1):25-9.
• 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.
• Smith DE, Walker BD, Cooper DA, et al. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? AIDS. 2004 Mar 26;18(5):709-18.
• U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. May 4, 2006. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7.