Primary HIV Infection: Why Early Detection Matters

Earlier this year, the New York City Commissioner of Health informed the public of a case of recently diagnosed HIV infection. The patient was infected with a multidrug-resistant strain of HIV, and his infection had progressed to symptomatic AIDS within a month of diagnosis. More worrisome still, the man had had unprotected sexual intercourse with numerous partners in recent months.

This case highlights the importance of detecting HIV infection in its earliest stages. Each year, 40,000 new cases of HIV infection are diagnosed in the United States¹; however, very few of these are identified at the acute infection stage. Diagnosis of primary HIV infection is important because it improves the patient's chances for a good outcome, reduces the risk of transmission, and provides epidemiologic data on virus strains in the community.

IMPROVED OUTCOMES

Although not conclusive, there is some evidence that early treatment lowers the virologic set point, or level of circulating virus. Higher set points have been associated with more rapid disease progression.² Thus, the hope is that lowering of the set point through early intervention will delay or prevent progression and the need for lifelong therapy.

In addition, detection represents an opportunity for the patient to enter regular care. Patients with HIV infection who receive regular care and follow-up usually have a better prognosis than those who do not.

PREVENTION OF TRANSMISSION

Diagnosis of HIV infection, which should always be accompanied by patient education regarding unsafe sexual practices and other risky behaviors, can do much to stop further spread of the disease. Early diagnosis is highly desirable. First, the shorter the time during which a person is unaware of his or her infection, the fewer the opportunities that person is likely to have to transmit HIV to others unknowingly. Also, patients are more infectious early in the natural history of HIV infection and are thus more likely to transmit the disease to sex or drug-using partners at this time.

EPIDEMIOLOGIC DATA ON VIRUS STRAINS IN THE COMMUNITY

Drug-resistant viral mutations typically replicate less robustly than do wild-type viruses. This means that in a person with HIV infection who is not receiving drug treatment, resistant mutations are not favored by natural selection; instead, more replication-competent variants do better. Thus, as HIV infection progresses untreated, the resistant mutations with which the person was infected sometimes revert to these more replication-competent strains. However, even though the drug resistance present at initial infection may eventually become undetectable, it is likely to rapidly reemerge once antiretroviral therapy is initiated.³

Thus, the importance of testing for drug resistance as early as possible in the course of infection is clear. The drug resistance of HIV found in newly infected persons more closely mirrors that of virus strains currently being transmitted in the community than does the resistance of HIV in persons who have been infected (but untreated) for some time. Hence, it enables researchers and public health officials to gain a more accurate picture of the types of drug-resistant strains currently being transmitted. Such information can help clinicians design treatment guidelines that take local patterns of drug resistance into account. In addition, early testing provides a more accurate picture of the resistance in an individual patient, which can help guide his treatment.

PATHOPHYSIOLOGY OF PRIMARY HIV INFECTION

Shortly after infection, HIV begins to replicate rapidly, unimpeded by the HIV antibodies that are just beginning to develop. Viral loads reach high levels (more than 1 million copies of HIV RNA per mL) at this time. In approximately 50% of infected persons, a transient flu-like illness known as acute retroviral syndrome, or primary HIV infection, develops--usually 1 to 4 weeks after exposure.⁴

Typical symptoms of primary HIV infection include fever, myalgia, rash, malaise, headache, sore throat, and lymphadenopathy. A number of other symptoms may also be present (Table). A wide range of laboratory abnormalities may be noted, including leukocytosis, elevated transaminase levels, and evidence of aseptic meningitis in the cerebrospinal fluid; however, none of these can be said to be typical.

The differential diagnosis of the conflux of symptoms commonly seen in primary HIV infection is very broad. The entity that most frequently comes to mind is mononucleosis. Others to consider include toxoplasmosis, group A streptococcal pharyngitis, influenza, and secondary syphilis. One clue that can help differentiate HIV infection from other diseases in the differential is symptomatology suggestive of a respiratory tract infection but without nasal congestion. Nasal congestion is less often seen in primary HIV infection.

Primary HIV infection is a self-limited illness that usually lasts 7 to 14 days. After symptoms subside, viral load declines and then becomes steady at a level known as the set point.

A THOROUGH RISK HISTORY--THE KEY TO DETECTION

Because the nonspecific symptoms of primary HIV infection can resemble those of a number of other very common entities, a thorough risk assessment is essential. Whenever a patient presents with a mononucleosis-like illness, it is worthwhile to ask about risky sexual and drug-using behaviors. In addition to the usual questions--about unprotected sex, anal intercourse, multiple partners, injection drug use--also ask about the behaviors of the patient's sexual partner(s) (eg, Does your partner use injection drugs? Has your partner had multiple sex partners?).

If a history of risk accompanies suspicious symptomatology, testing is recommended.

CONFIRMATORY TESTING

The HIV antibody test that is commonly used to diagnose HIV infection will not show a positive result for weeks to months after infection. Thus, it cannot be used to diagnose primary HIV infection. Instead, primary infection is diagnosed by detection of a high HIV load. Viral load can be measured by either an RNA assay or a p24 core antigen test; the RNA assay, which is regularly used to monitor the response to therapy of patients being treated for HIV infection, is more readily available.

A viral load of more than 10,000 copies/mL, together with a negative or indeterminate result on an HIV antibody test, is considered evidence of primary HIV infection.⁵ Typically, viral loads in patients with acute infection register in the tens of thousands or hundreds of thousands. Because false-positive results do sometimes occur, results of 50 to 10,000 copies/mL are considered indeterminate. For viral loads in this range, order a second test within 3 months and monitor the patient; at this point, antibody testing may also be appropriate.

WHEN TEST RESULTS ARE POSITIVE

If the results of an RNA assay and HIV antibody test are diagnostic of primary HIV infection, first reassure the patient and point out that early detection is associated with a greater likelihood of a good outcome. Next, refer the patient to an HIV or infectious disease specialist. If you are unfamiliar with the HIV specialists in your community, call the local health department or the local or state AIDS hotline.

Increasingly, HIV infection itself--not just AIDS--must be reported to the health department. Laws vary from state to state; be sure to keep abreast of the latest requirements for your locality. Such reporting, where required, is for epidemiologic purposes; the process has resulted in very few or no instances of breach of confidentiality.

References:

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Fox R, Eldred LJ, Fuchs EJ, et al. Clinical manifestations of acute infection with human immunodeficiency virus in a cohort of gay men.

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