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At 4 years, only 39% of individuals treated with HAART reached a CD4 T-lymphocyte count of 500/microL or greater, and 16% with CD4 T-lymphocyte counts less than 200/microL remained susceptible to opportunistic infections. Treatment interruptions, a poor virologic response, and older age were the major factors negatively affecting the recovery of CD4 T lymphocytes.

Background. The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration.Methods. Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load !1000 copies/mL for у5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (у500 cells/mL was defined as a complete response, and !500 cells/mL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses.Results. The median CD4 T cell count increased from 180 cells/mL at baseline to 576 cells/mL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau !500 cells/mL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders ( ). Older age (adjusted P 1 .05 odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21-2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28-0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19-4.81) were significantly associated with a CD4 T cell count !500 cells/mL at 5 years. The median increases in CD4 T cell count after 3-6 months of ART were smaller in incomplete responders ( ) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% P ! .001 sensitivity and 72% specificity.Conclusion. Individuals with incomplete CD4 T cell recovery to !500 cells/mL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3-6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes.

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considered.

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