Altered dynamics and differential infection profiles of lymphoid and myeloid cell subsets during acute and chronic HIV-1 infection

The dynamics of immune cell populations during acute HIV-1 infection are not fully deciphered, especially for non-T cells. In this study, we tested whether specific cellular subsets of the innate arm of the immune response are affected early after HIV-1 infection. Using a cohort of HIV-1-infected individuals, we have monitored the relative frequency of blood T lymphocytes, monocytes, and DCs at various infection stages and measured their respective intracellular HIV-1 DNA loads. The HIV-1 DNA load in naive CD4(+) T lymphocytes, which are lost very early during acute infection, was ten- to 100-fold lower than in CD57(-) and CD57(+) memory CD4(+) T lymphocytes. We observed that despite rapid, persistent loss after HIV-1 infection, pDCs represented a non-negligible HIV-1 DNA reservoir. CD16(+) proinflammatory cDCs and monocytes accumulated gradually, and HIV-infected CD16(+) monocytes contained higher HIV-1 DNA loads than their CD16(-) counterpart during acute infection. During chronic infection, CD16(+) cDCs exhibited higher HIV-1 DNA loads than the CD16(-) population. Overall, our results demonstrate that non-T cell compartments are a major HIV-1 DNA reservoir, and CD16(+) monocytes and CD16(+) cDCs potentially play an important role in HIV-1 dissemination. J. Leukoc. Biol. 89: 785-795; 201

Analysis of the effect of highly active antiretroviral therapy during acute HIV-1 infection on HIV-specific CD4 T cell functions

Background: It has been reported that antiretroviral therapy (HAART) during acute HIV-1 infection may rescue HIV-1-specific CD4 T cell responses. Objective: To determine the duration of this preserved response by investigating the long-term effects of HAART during acute infection on HIV-specific CD4 T cell function related to possible immune control during subsequent therapy interruption. Methods: A longitudinal analysis followed HIV-specific CD4 T cell reactivity in 17 individuals with well-documented acute HIV-1 infection where five out of 11 HAART-treated patients stopped therapy and six were untreated. Peripheral blood mononuclear cells were stimulated with overlapping peptide pools derived from Gag and Nef. Production of interferon-[gamma] (IFN-[gamma]) and interleukin-2 (IL-2) by CD4 T cells was analysed together with proliferative responses. Results: Absolute numbers, but not percentages, of Gag-specific IFN-[gamma]-, IL-2- or IFN-[gamma]/IL-2-producing CD4 T cells were increased in treated compared with untreated individuals up to 2 years after seroconversion. HAART during acute HIV-1 infection was associated with lower viral load but did not result in increased proliferation of HIV-specific CD4 T cells. One out of five individuals who discontinued therapy showed evidence for immune control. However, patients who failed to control viraemia also had measurable proliferative HIV-specific CD4 T cell responses and preserved numbers of cytokine-producing CD4 T cells. Conclusions: Early HAART during acute HIV-1 infection resulted in higher numbers of HIV-specific IFN-[gamma]- and IL-2-producing CD4 T cells, but this preservation in four out of five patients was not associated with control of viraemia upon treatment interruption

Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells. In all children and in adults with relatively high CD4 T cell counts at start of therapy (>200 cells/microl), total CD4 T cell numbers normalized within 1 year of therapy. After long-term HAART (4.4-9.6 years), naive CD4 T cell counts had normalized in both groups. Although in adults with low baseline CD4 T cell counts ( <200 cells/microl) total CD4 T cell numbers normalized eventually after at least 7 years of HAART, naive CD4 T cell counts had still not recovered. TCR excision circle data showed that thymic T cell production contributed to naive T cell recovery at all ages. The fraction of CD31-expressing naive CD4 T cells was found to be normal, suggesting that the CD4 T cell repertoire was diverse after long-term HAART. Hence, under sustained viral suppression during long-term HAART, the T cell compartment has the potential to fully recover by generating new naive T cells both in children and in adults with high baseline CD4 T cells counts. Irrespective of baseline CD4 T cell counts, reconstitution occurred without a significant effect on T cell aging as reflected by markers for replicative histor

Plasma viral load and CD4 cell count after randomization/treatment interruption in the no treatment and treatment arms.

<p>Modeled mean pVL (A) and CD4 cell count (B) over time after randomization/TI in the no treatment and the 24- and 60-wk treatment arms for the group of patients randomized over the three study arms. Graphs show the estimates (± standard error of the mean) from the linear mixed models. The box below each graph shows the number of pVL and CD4 cell count measurements at each time point used for fitting the linear mixed models. c/ml, copies/ml.</p

Baseline characteristics of 115 patients randomized over three study arms.

<p>Data are <i>n</i> (percent) unless indicated otherwise.</p>a<p>16 patients with missing data.</p>b<p>51 patients with missing data.</p>c<p>65 patients with missing data.</p>d<p>60 patients with missing data.</p><p>MSM, men who have sex with men; n.a., not applicable.</p