Background:  Effective ART promotes recovery of immune functions. We evaluated the changes in HIV-specific and -nonspecific cell-mediated immunity and circulating T cell phenotypes and the correlates of these characteristics with control of viral replication and increase of CD4⁺ cells in response to a first HAART regimen.

Methods:  We studied 37 ARV-naïve children, 3 to 21 years of age, who initiated didanosine (ddI), emtricitabine (FTC), and efavirenz (EFV) were tested at weeks 0, 16, 24, and 48 by ELISpot using HIV inactivated whole virion to estimate CD4⁺ responses (HIV_CD4); 7 HIV peptide pools to estimate CD8⁺ responses (HIV_CD8), and Candida, and by T cell immunophenotyping. The median CD4⁺ and plasma HIV RNA at weeks 0 and 48 were 17% and 47,775 copies/mL, and 33% and <50 copies/mL, respectively.

Results:  At entry, the median HIV CD4, HIVCD8, and Candida spot-forming cells (SFC)/10⁶ mononuclear cells were 20, 5731, and 35, respectively. Positive associations existed between entry Candida SFC and CD4⁺ cells and HIV CD8 SFC and plasma HIV RNA. Candida and HIV CD4 SFC increased on HAART reaching significant and marginally significant, respectively, changes by week 16. In contrast, HIVpp decreased over time. Week 16 Candida SFC was negatively associated with plasma HIV RNA. Week 48 HIV CD4 SFC increased with higher pre-HAART HIV CD4 SFC. Naïve (CD45RA⁺CD62L⁺) and CD28⁺ T cells increased on HAART, whereas activated (CD38⁺HLADR⁺) and CD95⁺ T cells decreased over time. Activated T cells correlated with plasma HIV RNA before, but not after HAART initiation. While on HAART, there were positive associations between activated T cell percentages and Candida and HIV CD4 SFC. With respect to the predictive value of baseline measures, higher CD4⁺, CD4⁺ naive and lower CD4⁺ activated cell percentages were associated with higher CD4⁺ cells at week 48; broader HIV CD8 responses marginally correlated with shorter time to plasma HIV<50 RNA copies/mL.

Conclusions:  HAART was associated with a more robust increase of Candida- than HIV-specific immunity. During HAART, decreased viral replication and higher frequencies of activated T cells correlated with higher Candida and HIV CD4 SFC. HIV CD4 responses increased with higher pre-HAART values. The best immunologic predictor of virologic response to HAART was the breadth of HIV CD8 responses, whereas high frequency of naïve, low frequencies of activated cells, and low plasma HIV RNA pre-HAART correlated with higher CD4⁺ cells after 1 year of effective treatment.