Primary HIV infection (PHI) refers to the period of time immediately after initial infection, which is characterized by a prolific phase in viral replication (sometimes up to one million copies of virus) and an acute drop in the CD4 count. However, the HIV antibody is negative, because it has not yet had time to develop. (It usually takes 1-3 months for detectable levels of antibody to HIV to develop.) Identifying individuals during this initial phase of infection is important not only to the newly infected person, but to the community as well.

The most common symptoms of PHI include fever, lymphadenopathy (enlarged "glands"), pharyngitis (sore throat), and rash. These symptoms generally manifest two to four weeks after exposure to HIV. Although PHI often is symptomatic, the symptoms are very non-specific. A diagnosis of PHI may be overlooked since the symptoms are similar to and at times indistinguishable from the flu or another flu-like illness. Plus, since self-limited, people usually do not seek medical attention during this critical time.

Persons with PHI are, however, thought to be extremely infectious because of the high viral load and high levels of genital shedding found. In one small study, five people with PHI and their partners who subsequently developed PHI were enrolled. The study revealed that HIV is highly transmissible by sexual intercourse during PHI even days before the onset of PHI symptoms. The increased risk of HIV transmission during primary infection is a significant public health concern and emphasizes the need for identifying newly infected persons. However, as noted above, several barriers exist that hinder easy identification of persons during this period of initial infection.

Over the past decade, the trend in HIV care has been to delay initiation of antiretroviral therapy until the CD4 count has dropped significantly. The one exception is persons identified during the period of primary HIV infection. Highly active antiretroviral therapy (HAART) during PHI has produced a shorter symptomatic period and rapid suppression of viral replication. In one study persons with primary HIV infection treated with 2 reverse transcriptase inhibitors and a protease inhibitor had immediate reductions of viral load. Individuals also had significantly decreased incidence of oral and esophageal candidiasis as well as less respiratory complaints.

Treatment during PHI may be protective against rapid progression to AIDS. Bruce Walker and others have shown that HAART for one year may preserve the HIV-specific immune response (your body's ability to fight HIV), leading to long-term "non-progression". Since starting HAART during PHI has not been well studied, once started, it is unclear how long one needs to continue on the medications to have this long-term benefit. One small study by Sarah Fidler and others, presented at the International AIDS Conference this year, found that just a short course of HAART (SCART) after initial HIV infection until the viral load becomes undetectable (4 to 32 weeks) may help keep the immune function against HIV intact. After HAART was stopped, although every participant's viral load rebounded, several people remained at a lower set point. More studies are needed to confirm this, but potentially SCART may reduce the long-term need for HAART, thus minimizing toxicity and costs. Unfortunately, despite the early treatment, however, it has been well documented that the virus is never completely eradicated.

Selecting an initial HAART regimen in primary HIV infection is becoming more and more complicated as viral resistance is increasing. A retrospective study of approximately 200 antiretroviral-naive people revealed increasing drug resistance to non-nucleoside reverse transcriptase inhibitors in primary HIV infection from 0 percent in the mid-1990s to 8 percent in 2000-2001. Therefore, resistance testing is now recommended for some newly infected persons who have never been on HAART before, especially in areas of the country with higher rates of resistance. Overall, resistance in antiretroviral-naive people still remains uncommon, but those persons with drug-resistant infections appear to take longer to virally suppress and have a shorter period of time to drug failure.

It is therefore important to educate both the public and healthcare providers on how to recognize primary HIV infection, to increase the number of people diagnosed during the critical period of initial infection. It is important not only to minimize transmission to others, but appears that treatment during PHI may alter HIV progression over time.