Important note: Information in this article was accurate in December 1998. The state of the art may have changed since the publication date.The Primary Infection Clinic began in September of 1992 with the goal of following the natural history of early/acute HIV, an area about which very little was known at the time.
In the past 5 years, partly as a result of our work, knowledge surrounding acute or primary HIV has grown from a suspicion about a viral conversion syndrome to a well-described clinical symptom complex of pharyngitis, fever, and fatigue 1.
The variation of symptoms and severity of illness among individuals is marked, and may range from a mild sore throat that lasts only a couple of days, to high fevers, rash, and headache that require hospitalization. The most common symptoms reported in our natural history study at the University of Washington are fever and/or night sweats, sore throat, headaches, muscle aches (similar to those experienced with the flu), fatigue, and rash.
Dr. Phillipe Vanhems of France recently compared our data to two primary infection clinics in Geneva, Switzerland and Sydney, Australia. He found reassuring evidence that the same symptoms we see here in individuals seroconverting were seen in both Australia and Switzerland. Other symptoms seen less frequently in all three clinics were oral and genital ulcers, swollen lymph nodes, diarrhea, and anorexia (loss of appetite).
Our recent data suggest that individuals with more severe syndromes, i.e., those who present to medical attention, may have a more rapid progression to clinical AIDS2, suggesting a strong need to identify all such cases early and to offer early treatment. Local HIV/AIDS epidemiologists in the State Department of Health and the Seattle-King County Department of Public Health estimate that we continue to have 600 to 900 seroconversions per year in this state, possibly half of which have a symptomatic seroconversion syndrome3.
We know from our data that only about half of persons with HIV who present to their medical provider with symptoms will be screened for HIV antibody. We hope that reminding the public and providers about primary HIV will increase the number of infections caught early on. Symptoms are not required for enrollment in the Primary Infection Clinic, however. I have outlined our criteria below, but we are happy to perform all screening bloodwork.
After an initial behavioral-risk-factor interview, consent forms are signed to allow blood to be studied for antibody, viral load testing (plasma RNA), proviral HIV detection (DNA PCR), CD4+ cell count, and cellular response to the potential HIV infection (cytotoxic T-lymphocytes). During very early HIV infection, the anti-HIV antibody (the antibody that is detected on the standard screening test) may remain negative for 6 weeks after the infecting exposure, so it is important to test for HIV RNA in the plasma, which may be detectable within 10 days after exposure. It takes a week to get the viral load (RNA) back from the lab; at that time we review the results and discuss potential studies for enrollment, which I discuss below.
Our contribution to the current understanding of early HIV infection has recently been recognized with a 4-year, multi-site, $6.7 million/year grant from the National Institute of Allergy and Infectious Diseases for the continuation of our studies. The Aaron Diamond AIDS Research Center, the University of California at San Francisco, Johns Hopkins University School of Medicine, the University of Colorado Health Sciences Center, and the University of Alabama at Birmingham will be collaborating with us on the Acute Infection and Early Disease Research Program. We have established a cooperative network with clinics in Minnesota (Tim Schacker); Cincinnati (Judith Feinberg); National Institute of Health (Anthony Fauci); Sydney, Australia (David Cooper); and Geneva, Switzerland (Luc Perrin) to better understand the evolution of the infecting virus, the cellular immune response of the host (particularly the early defect in immune response), emergence of the neutralizing antibodies, and how pharmaceutical intervention may impact all of these.
Acute seroconvertor. An individual with an acute seroconversion syndrome with corresponding labs bDNA-positive and EIA- negative, or EIA-positive, with indeterminate western blot converting to positive
Asymptomatic seroconvertor; An individual with a negative antibody test within the last 6 months, who has a positive test now (no seroconversion symptoms)
Symptomatic seroconvertor; An individual with a negative antibody test within the last 12 months, a positive EIA now, and with a seroconversion syndrome within the last 3 months.
The Primary Infection Clinic's natural history study enrolls individuals who meet the above-listed criteria to better define the clinical, virologic, and immunologic characteristics of primary HIV. The study provides free laboratory tests including viral load testing and CD4 counts, and offers optional testing of semen viral load and lymph node biopsies. The study is ongoing and is not limited to a maximum number of participants.
We are currently enrolling in a trial of "triple" drugs: AZT (zidovudine), 3TC (lamivudine), and indinavir (Crixivan) to study the effects of early intervention on the mutations of the virus, the viral replication rates, CD4+ cell counts, and other measures of immune system integrity. The study provides free medication for 12 months, as well as free lab tests during the study. The study is limited to persons infected within the last 3 months (with a recent negative EIA or with symptoms suggestive of recent infection), and will include a maximum of 10 enrollees.
The International Acute Infection and Early Research Network grant funded by the NIH will also include a pharmaceutical intervention with multiple antiretrovirals. This trial will begin enrollment around the first of 1998. Medications will be provided, as will frequent lab monitoring.
Drug treatment during primary HIV has the theoretical benefit of attacking HIV when the virus has perhaps not established a foothold in the body, when the immune system is strongest, and while a relatively homogeneous strain of virus still predominates. However, there is also real concern that we may be using up our "magic bullet" too soon -- that over the long haul early therapy will not always be optimal. And, of course, there are toxicities with all these drugs.
The trials performed in our clinic are designed to observe clinical as well as viral and immunologic parameters in early intervention, and will, we hope, reveal some of the predictors that may help us be able to decide very early whether someone would benefit from very early intervention, or whether his or her own immune system will be able to control the virus.
To answer questions means we need to see people and enter them into clinical trials. Our approach is to allow individuals to select their therapeutic approach with their primary care providers, although we are certainly available at any time to help with therapeutic decision-making. Through the new Madison Clinic at Harborview we can also provide primary care for those people who do not have a regular provider.
Please feel free to contact us at any time with questions at 206-667-5300, or toll-free within the state of Washington at 800-968-1437.
You can also reach the clinic via e-mail at mmb@u.washington.edu. Although we hope for the fewest possible seroconversions, it is our hope to have every case of early HIV identified and referred to us.
Michelle Berrey is the clinic physician at the Primary Infection Clinic. She has been doing clinical research in primary HIV infection since 1996.
1Schacker T, Collier AC, Hughes J, Shea Y, Corey L. "Clinical and epidemiologic features of primary HIV infection", Ann Intern Med 1996 Aug 15;125(4):257-64.
2 Schacker TW, Hughes JP, Shea T, Coombs RW, Corey L. The natural history of primary HIV infection (in press)
3 Personal communication, Bob Wood, MD. Seattle-King County Department of Public Health, January 1997.
980101
STEP9304
Copyright © 1998 - Seattle Treatment Education Project, 1123 East John Street, Seattle, WA 98102. (206) 329-4857 or (877) 597-STEP [7837] (toll-free, valid only in the Pacific Northwest: Washington, Oregon, Idaho, Alaska, and Montana) e-mail: step100@aol.com
ÆGiS is made possible through unrestricted grants from Roxane Laboratories, Inc., iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.
ÆGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1985, 2000. ÆGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on ÆGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS and the Sisters of Saint. Elizabeth of Hungary, or the party credited as the provider of the content.