Primary HIV Infection
Acute retroviral syndrome occurs at the time the infection is acquired in 60% to 80% of HIV-infected persons. The illness resembles infectious mononucleosis from infection with Epstein-Barr virus (EBV), and acute retroviral syndrome is a consideration in differential diagnosis of heterophil-negative mononucleosis. Risk factors for transmission of HIV include history of a sexually transmitted disease, especially genital ulcers; unprotected anal or genital intercourse; and multiple sexual partners.
Clinical signs and symptoms
The period between acquisition of HIV and onset of symptoms is about 14 days, and the characteristic signs and symptoms range from a mild fever and sore throat to a severe mononucleosis-type syndrome with high spiking fevers and a measles-like rash.
In those patients with symptomatic seroconversion, the five most common signs and symptoms are fever, fatigue, pharyngitis, weight loss, and myalgias. Characteristic symptoms of acute retroviral syndrome occur in 50% to 90% of patients.
| Differential Diagnosis of Primary HIV Infection |
| Epstein-Barr virus mononucleosisPrimary cytomegalovirus infection
Primary herpes simplex virus infection Viral hepatitis Rubella Toxoplasmosis Secondary syphilis Measles Disseminated gonococcal infection Drug reaction |
| Signs and Symptoms of Primary HIV Infection | |
| Feature | Frequency (%) |
| FeverFatigue
Pharyngitis Weight loss Myalgias Headache Nausea Cervical adenopathy Night sweats Diarrhea Vomiting Rash |
9590
70 68 60 58 58 55 50 50 40 35 |
Laboratory features
Primary HIV infection is diagnosed by a positive plasma HIV RNA obtained on the same day as a negative Western blot assay. If the interval between onset of symptoms and ordering of the HIV RNA test and Western blot assay is prolonged, both tests will be positive, suggesting that the patient has been infected with HIV for an extended period.
Clinical evaluation of possible primary HIV infection often includes a heterophil antibody (Monospot) test to rule out EBV mononucleosis, cytomegalovirus antigen or antibody, acute and convalescent serologic tests for rubella and toxoplasmosis, rapid plasma reagin test, Western blot assay for herpes simplex virus, and serologic tests for hepatitis (including hepatitis C virus RNA polymerase chain reaction). Because up to 30% of mononucleosis syndromes caused by EBV are heterophil-negative, other serologic tests for EBV may be necessary as well (eg, EBV IgM, IgG, early antigen, and nuclear antigens).
Initial management
When the diagnosis of primary HIV has been established, the patient should be examined for syphilis, herpes simplex, venereal warts, gonorrhea, and hepatitis.
If the patient is not infected with hepatitis A or B, vaccination should be considered. If the patient was identified as HIV RNA-positive and HIV EIA-negative, a follow-up HIV antibody test should be obtained 2 to 3 weeks after resolution of symptoms to establish that seroconversion has taken place.
A baseline CD4+ T-lymphocyte count should be obtained at the time of diagnosis. In the earliest stages of infection, the CD4+ count can sometimes be below 200 cells/µL. After the first several weeks of infection, a rebound in the CD4+ count to near normal levels may occur.
Baseline quantitative HIV RNA measurement should be obtained. In patients with severe symptoms of HIV seroconversion, viral titers may exceed 50 million copies/mL of blood. Viral titer falls rapidly after the first few weeks of infection, sometimes to undetectable levels.
Therapy during primary HIV infection
Viral loads are very high in the first weeks and months of HIV infection, and intervention at this time may ultimately result in a significant decrease in overall viral burden.
The therapeutic regimen for acute HIV infection should include a combination of two nucleoside reverse transcriptase inhibitors and one potent protease inhibitor. Potential combinations of agents are much the same as those used in established infection and include the following regimens:
Two nucleosides reverse transcriptase inhibitors plus a protease inhibitor2 NRTIs and 1 protease inhibitor
Zidovudine ( AZT, Retrovir 300 mg PO bid) + lamivudine ( 3TC, Epivir 150 mg bid), didanosine ( ddl, Videx), or zalcitabine ( ddC, Hivid) + potent protease inhibitor ( indinavir, Crixivan 800 mg q8h) or
Stavudine ( d4T, Zerit) + lamivudine or didanosine + potent protease inhibitor
Two nucleosides plus a non-nucleoside reverse transcriptase inhibitor:
Zidovudine (AZT, Retrovir) + lamivudine, didanosine, or zalcitabine + nevirapine (Viramune) or delavirdine mesylate (Rescriptor) or
Stavudine + lamivudine or didanosine + nevirapine or delavirdine.
Triple-drug therapy may result in a significant clinical benefit when instituted as soon as possible after HIV acquisition. Once therapy is initiated it should be continued indefinitely because viremia may reappear or increase after discontinuation of therapy.
Postexposure prophylaxis
Combination chemotherapy results in fewer transmissions, and use of combination chemotherapy, including a protease inhibitor, is suggested following a significant intravenous exposure.
Postexposure prophylaxis should also be initiated following sexual exposure.
Postexposure prophylaxis treatment regimens
Zidovudine (ZDV): 300 mg PO bid and
Lamivudine (3TC, Epivir): 150 mg bid
Protease Inhibitor: Indinavir ( Crixivan) 800 mg q8h or Nelfinavir 750 mg tid (if needed to ensure 2 new antiviral drugs or for very risky exposure).