Viral and Immunologic Studies in 30 Long-Term Survivors with Nonprogressive HIV-1 Infection


Viral and Immunologic Studies in 30 Long-Term Survivors with Nonprogressive HIV-1 Infection

Seattle Treatment Education Project (STEP) Perspective, Vol. 7, No. 1 - Spring 1995; A Publication of the Seattle Treat- ment Education Project, 127 Broadway E. Ste. 200, Seattle, WA 98102 * (206) 329-4857. Published 3 times a year
Jeffrey T. Schouten, MD

On January 26, 1995 the New England Journal of Medicine published three studies of persons infected with HIV-1 for over ten years who had no significant immunologic deficiencies.[1,2,3] The term used to define this group of persons is long-term nonprogressors. This rather technical sounding term is used to differentiate this small group of persons, estimated to be about 5-8% of all persons infected with HIV, from persons who survive HIV infection for more than ten years, but have some evidence of HIV-related illness or immune surpression.[4] Overall, 50% of all persons infected with HIV develop symptoms related to HIV or immunologic surpression within 10 years.[5] Generally, the term long-term survivor is used to refer to persons who have been infected with HIV for over ten years and have remained relatively healthy. The term long-term nonprogressor refers to a subgroup of long-term survivors who have an intact immune system, despite being infected for over ten years. For the purpose of these studies, long-term nonprogressors were defined as persons who were infected with HIV for over 10 years, had received no antiretroviral therapy, and had no evidence of HIV-associated illnesses.

Long-term nonprogressive HIV infection is of interest for several reasons. First, these studies were done to determine if there are "host factors" which render a person "immune to HIV infection". Do long-term nonprogressors have some unique factors such as, cellular defenses, antibodies, immunologic markers, tissue types, etc., to explain why they are able to resist damage to their immune system? Secondly, these studies were undertaken to see if these persons had evidence of ongoing viral replication. Also, the investigators sought to find out if the strain of virus that these persons were infected with was different from the usual strain of virus infecting persons who develop immune surpression and AIDS.

Dr. David Ho's group at New York University studied 10 people, 9 men and 1 woman, ranging in age from 38 to 47 years6. All had normal CD4 counts throughout the course of their infection. All subjects were found to have very low levels of virus. HIV could not be cultured from the peripheral blood of any of the subjects, but more sensitive tests looking for viral RNA and DNA did show HIV to be present. Evidence of a strong immune response to HIV was found, including HIV-1 specific antibodies and a strong surpressive response by CD-8 lymphocytes. The level of virus found in two of the persons was surprising high and the virus isolated reproduced very efficiently in vitro. Thus, the lack of immune surpression cannot be attributed solely to infection with a weak, or non-virulent strain of HIV. Dr. Ho concluded this report by noting that the strong immune response observed and low levels of virus observed would support therapies which reduce the burden of HIV-1 to levels seen in long-term survivors, or below.

Dr. Anthony Faucci's group at the National Institute of Health reported on 15 persons with long-term nonprogressive HIV infection, 14 men and 1 woman, ranging in age from 33 to 467. Lymph node biopsies were performed to examine lymphatic structure. Unlike most persons with HIV infection, the long-term nonprogressors showed no destruction of lymph node architecture, indicating a more effect control of HIV. Plasma levels of HIV RNA and viral levels were lower than those in persons with progressive HIV infection. As in Dr. Ho's study, HIV could not be cultured from the plasma; however, HIV was cultured from the lymph nodes in 7/14 persons.

The third study, from the Harvard Medical School, studied HIV isolated from 5 long-term nonprogressors8. The virus isolated from one patient was found to be unique, it lacked a gene necessary for replication, the nef gene. Apparently, this person was infected with a defective form of HIV which immunized him to infection by other strains of HIV. This appears to be a very rare situation. This form of the virus has been used to immunize monkeys with a live virus. However, recently this form of the virus was reported to cause immunodeficiency in newborn monkeys.[9] Other than this one case, persons with long-term nonprogressive HIV seem to be infected with the same strains of HIV as persons with progressive HIV infection.

An accompanying editorial to three articles pointed out that persons infected with HIV only carry one strain of HIV and seems to be immune to infection with other strains of HIV10. The immune system appears to be able to keep viral levels low enough in 5-8% of persons infected with HIV so that the immune system is able to remain healthy indefinitely. It is important to emphasize that persons with nonprogressive HIV infection still have virus present in their system and are potentially infectious. Persistent viral replication was observed in almost all of the persons with long-term nonprogressive HIV infection. Also, persons who are HIV-positive should follow safer sex guidelines if sexually active with other HIV-positive persons because infection with a more virulent HIV strain is possible (even though it does not usually occur) and other sexually transmitted diseases , such as herpes, may accelerate the course of HIV infection.

Jeffrey Schouten is a general surgeon and co-chair of STEP's Scientific Review Committee.

1. Cao Y, Qin L, Zhang L, Safrit J, Ho DD. Virologic and Immunologic Characterization Of Long-Term Survivors Of Human Immunodeficiency Virus Type 1 Infection. N Eng J Med 1995;332:201-8.

2. Pantaleo G, Menzo S, Vaccarezza M, et al. . Studies In Subjects With Long-Term Nonprogressive Human Immunodeficiency Virus Infection. N Eng J Med 1995;332:209-16.

3. Kirchhoff F, Greenough TC, Brettler DB, Sullivan JL, Desrosiers RC. Brief Report: Absence Of Intact nef Sequences In A Long-Term Survivor With Nonprogressive HIV-1 Infection. N Eng J Med 1995;332:228-32.

4. Buchbinder SP, Katz MH, Hessol Na, et al. Long-term HIV-1 infection without immunologic progression. AIDS 1994;8:1123-8.

5. Rutherford GW, Lifson AR, Hessol NA, et al. Course of HIV-1 infection in a cohort of homosexual and bisexual men: an 11 year follow up study. BMJ 1990;301:1183-8.

6. Ibid #1.

7. Idib #2.

8. Idib #3.

9. Note: At Conference, Hope for Success Is Further Attenuated. Science 1994;266:1154 Nov 16

10. Baltimore D. Ed:Lessons From People With Nonprogressive Infection. N Engl J Med 1995;332:259-60.

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