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Primary HIV Infection and Post Exposure Prevention

Introduction

Most HIV-infected individuals, even those with minimum levels of replicating virus, would benefit from treatment and, therefore, aggressive treatment with effective combinations of antiretrovirals should span the spectrum of those with HIV infection, irrespective of their immune competence and not be limited to those with advanced degrees of immune suppression. This includes treatment for those with primary HIV infection and may apply to those with HIV exposure as part of a comprehensive prevention program including education and counseling for subsequent exposure risk reduction.

Prompt and early treatment following exposure may prevent occupational acquired HIV infection among healthcare workers (2). Treatment for infected women during pregnancy and then continued in their newborn children reduces the rate of "vertical transmission" from these infected mothers to their children (3). Other studies have demonstrated that treating people prior to immune destruction, reduces viral load and improves clinical outcomes, led investigators to a strategy aimed to treat persons at the earliest stage of HIV infection, ie, during primary HIV infection (4). It was hoped that effective therapy, begun prior to viral dissemination and entry into sanctuary sites, prior to when the virus has mutated; and at a time to augment the immune system's attempt to control viral replication, may lead to an effective HIV suppression strategy. The early suggestions of eradication may prove impossible; but identifying those with early infection may have important consequences for individuals to reduce their biologic set point.

Pathogenesis of Primary HIV Infection

The events of primary infection has been studied in the simian immunodeficiency virus (SIV) model of acute infection (8-10). In this model, SIV is detected in the regional lymph nodes of macaques within a few hours after inoculation. Active viral replication occurs in lymph nodes within five days following inoculation. Individual cells expressing SIV can be detected by in situ hybridization.

Early Identification of People with Primary HIV Infection

The signs and symptoms of primary HIV infection are relatively nonspecific and can be confused with a variety of acute illnesses. In addition, HIV infection is not as common as the other infections that enter the differential diagnosis of primary HIV infection. Thus, many persons with suspected primary HIV infection due to a possible exposure ultimately will not have documented HIV infection as the explanation for the acute illness. This represents an important opportunity to engage these high-risk individuals and to enroll them in HIV risk-reduction programs and is a critical issue for

Signs, Symptoms and Laboratory Evaluation of Primary HIV Infection

Initial or primary HIV infection is often accompanied by signs and symptoms of an acute viral infection. These signs and symptoms are listed in Table 1. The symptoms usually present within days to weeks after initial exposure and subsequent infection. Up to 80% of newly infected individuals will report a history of a viral illness and most will seek medical attention from primary care physicians, emergency rooms, sexually transmitted disease clinics, dermatologists, and other clinical settings. The most common signs and symptoms of initial HIV infection include fever, fatigue, rash, and headache. Other common signs or symptoms include lymphadenopathy; pharyngitis; myalgia; arthralgia; retro-orbital pain; weight loss; depression; gastrointestinal distress characterized by nausea, vomiting, or diarrhea; night sweats; and oral ulcers.

Rationale for Treatment of Primary HIV Infection

Support for the concept of treatment during primary HIV infection comes from recent observations that show that HIV may be more vulnerable to effective combination therapy during primary infection. Early in the course of infection the immune system remains relatively intact although the rate of loss of CD4 cells may be increasing with contemporaneous primary HIV infection. Newly infected persons tend to have a relatively homogeneous swarm of viruses, whereas persons with long-term infection have a diverse swarm of viruses. The low degree of diversity among viral isolates soon after initial infection suggests that there are relatively few resistant isolates; these have developed not as a result of selective pressure, but because of the replicative infidelity of HIV and the replicative tolerance of various isolates that may harbor resistant genotypes. Thus, the low numbers of resistant isolates may enhance the efficacy of treatment during primary HIV infection.

If replication can be completely halted in all body compartments and if treatment can maintain cessation without replication in all body tissues for years, eradication is believed possible. However, many questions regarding integrated but non-replicating virus remain unanswered. In addition the are

Treatment of Persons with Primary or Early HIV Infection

Specific limitations regarding published investigations of the treatment of primary HIV infection are that the definition of primary infection is imprecise or has been applied to cohorts that are not comparable. In general, primary HIV infection has been confused with early or recent HIV infection. Treatment of people with early HIV infection has been tested in a randomized, double-blind, placebo-controlled clinical trial.