Long-Term Follow-Up of HIV-Infected Individuals Who Have Significant Increases in CD4+ Cell Counts during Antiretroviral Therapy

Descriptions of the durability and consequences of immune reconstitution in patients who start highly active antiretroviral therapy (HAART) while severely immunosuppressed are limited.

Patients with previous CD4⁺ cell counts <50 cells/mm³, all of whom had HAART-induced increases in CD4⁺ cell counts of >100 cells/mm³ on 2 separate occasions (measured sequentially at least 4 weeks apart), were enrolled in a prospective trial and observed every 1632 weeks. Evaluations included assessments for new opportunistic complications, virologic and immunologic (CD4⁺ cell count) responses, or death.

Results     

The median follow-up duration for 612 subjects was 184 weeks (range, 8--216 weeks). The rate of increase in CD4⁺ cell counts was ~5.9 cells/mm³ every 8 weeks, with the degree of increase associated with the baseline HIV RNA load (<500 vs. ≥500 copies/mL).

Subsequent measurements of virologic suppression based on HIV RNA levels were also associated with predicted CD4⁺ cell responses.

Thirty-three AIDS-defining illnesses were reported (1.75 events per 100 person-years of follow-up); >40% (14 cases) occurred with higher than expected CD4⁺ cell counts.

Conclusions   

In conclusion, the authors write, “CD4⁺ cell count increases are related to virological control, with continuing increases seen in individuals who are immunosuppressed. Opportunistic illnesses and/or complications are infrequent but can occur at any time, even in patients who maintained an elevated CD4⁺ cell count.”

Commentary

There were remarkably low numbers of AIDS-defining illnesses over a prolonged follow-up period (1934 person-years) in this study of HIV-infected individuals who had previously been severely immunosuppressed but who had responded to HAART.

In the majority of cases, opportunistic illnesses occurred in the context of decreases in CD4⁺ cell counts and suboptimal control of virologic replication. In those cases in which the CD4⁺ cell counts were uncharacteristically high, diagnoses were more often presumptive or clinical presentations were atypical.

These observations are in dramatic contrast to the historically high risk of life-threatening opportunistic illnesses and generally poor prognosis for untreated HIV-infected individuals who have markedly diminished CD4⁺ cell counts.

Even without maximal virological suppression, some degree of immune recovery occurs following HAART. Because the GEE models used in this analysis should be considered to be exploratory, confirmation warrants further studies in the context of dynamic CD4⁺ cell counts and HIV RNA responses. Opportunistic illnesses and/or complications (including death) are relatively infrequent but can occur at any time, even for patients who maintained increases in the CD4⁺ cell count.

Division of Infectious Diseases, Ohio State University, Columbus, Ohio; Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts; Division of Infectious Diseases, University of CaliforniaSan Diego School of Medicine, San Diego, and University of California at Los Angeles, Los Angeles, California; Infectious Diseases Unit, University of Rochester Medical Center, Rochester, New York; Northwestern University, Chicago, Illinois; and Eudowood Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

11/17/04

Reference
S L Koletar and others (for the AIDS Clinical Trials Group 362 Study Team). Long-Term Follow-Up of HIV-Infected Individuals Who Have Significant Increases in CD4⁺ Cell Counts during Antiretroviral Therapy. Clinical Infectious Diseases 39(10): 1500-1506. November 15, 2004.