Natural History of HIV Supports the Use Of Early Interventions

NEW YORK--The more that is learned about the natural history ofthe human immunodeficiency virus (HIV), the stronger the casefor early intervention. Recent research confirms "the notionthat HIV infection is a dynamic process throughout the courseof infection," said H. Clifford Lane, MD, clinical director,National Institute of Allergy and Infectious Diseases (NIAID).

Speaking at a CME program on the management of HIV-infected patients,jointly sponsored by the Center for Bio-Medical Communicationand AmFAR (American Foundation for AIDS Research), Dr. Lane saidthat the dynamic balance between viral burden and CD4+ T celllevels remains the primary indicator of the progress of the disease(see box).

Within 3 to 6 weeks of primary infection, levels of virus areobserved to peak and then begin to decline. It is hypothesizedthat this indicates the beginning of an immune response.

"The strength of the immune response at this critical junctureseems to have a long-lasting impact on the patient," he said.Patients who are able to control the virus, as evidenced by lowlevels of HIV RNA and diverse T-cell immune response, do muchbetter than those whose response is more restricted and whoselevels of HIV RNA are higher.

Clinically, those patients with the most severe symptoms tendto be the ones who show the highest propensity for rapid progression,he said.

Nonetheless, the majority of patients eventually experience adecline in CD4+ T cell count and an increase in viralburden, resultingin disease progression. It now appears that so-called long-termnonprogressors are merely part of a continuum, Dr. Lane commented.

He said that certain qualitative changes in the immune systemhave profound implications for therapeutic intervention and underlinethe importance of intervening at the earliest possible moment.

"As HIV progresses, elements of the T cell repertoire areprogressively lost," Dr. Lane said, "and the increasesin CD4+ cells one sees in the context of treatment are due toexpansion of the remaining elements of the T cell repertoire ratherthan the entry of new elements."

Monitoring theProgression of HIV

In his talk in New York (see story above), Dr. H. Clifford Lane,of the NIAID, said that laboratory monitoring of HIV-infectedpatients is an essential element of disease management.

Although several new laboratory tests are available, includingassays for HIV RNA, he said that the CD4+ T cell count remainsan important and reliable indicator of disease progression.

Patients with CD4+ T cell counts under 200/mL are at an increasedrisk of Pneumocystis carinii pneumonia (PCP), he said, while thosewith CD4+ counts under 100/mL are at an increased risk of infectionwith cytomegalovirus and Mycobacterium avium-intracellulare.

Dr. Lane recommends a baseline CD4+ test at diagnosis, to be repeatedevery 6 months or more often if a declining trend is noted.

CD4+ count below 500 is a licensed indication for antiretroviraltherapy, and a declining trend may suggest the need to changethe therapeutic regimen. Patients with CD4+ counts below 200 shouldbe placed on a regimen for PCP prophylaxis, he said.