Pregnancy in women with perinatally acquired HIV-infection: Outcomes and challenges

This is a retrospective comparison of pregnant women with perinatally acquired HIV-infection (PAH) with a cohort of pregnant women with behaviorally acquired HIV-infection (BAH). PAH cases (11 women) included all pregnant adolescents followed at our HIV clinic from January 2000 to January 2009. BAH cases (27 women) were randomly selected from all deliveries within the study period at the same institution. Demographics, mode of delivery, CD4+ counts, and viral loads (VLs) before, during, and six months postpartum, as well as neonatal outcomes, were reviewed

Immunodominance of HIV-1 Specific CD8+ T-Cell Responses Is Related to Disease Progression Rate in Vertically Infected Adolescents

BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. CONCLUSIONS/SIGNIFICANCE: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions

Selective Loss of Innate CD4(+) Vα24 Natural Killer T Cells in Human Immunodeficiency Virus Infection

Vα24 natural killer T (NKT) cells are innate immune cells involved in regulation of immune tolerance, autoimmunity, and tumor immunity. However, the effect of human immunodeficiency virus type 1 (HIV-1) infection on these cells is unknown. Here, we report that the Vα24 NKT cells can be subdivided into CD4(+) or CD4(−) subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4(+) and CD4(−) NKT cells frequently express both CXCR4 and CCR5 HIV coreceptors. We find that the numbers of NKT cells are reduced in HIV-infected subjects with uncontrolled viremia and marked CD4(+) T-cell depletion. The number of CD4(+) NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4(−) NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4(+) NKT cells relative to regular CD4(+) T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4(+) lymph node homing (CD62L(+)) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4(−) CD62L(−) phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients

Categorization of subjects into two distinct disease progression groups.

<p>Two examples of representative patients categorized into either long-term survivors with No Immune Suppression (NS) (A) or Severe Immune Suppression (SS) (B). The dotted line is the boundary of the CD4% value of that progression group. The shading shows the window from within which PBMC samples were chosen for study.</p

Distribution of HLA class I alleles in study Cohort.

<p>The frequency of expression of HLA class I A alleles (A) and B alleles (B) among the two progression groups in the cohort was compared to the expected frequency in a Hispanic and African American cohort (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021135#s4" target="_blank">methods</a>). Associations between HLA Class I alleles and clinical characteristics are shown in panels C–F. Associations between log viral load (LCL) of all subjects and class I HLA-A alleles (C) and B alleles (D), are ordered from lowest LVL to highest. Associations between CD4% values and HLA Alleles (E) and B alleles (F) are ordered from highest CD4% to lowest. The solid line in each column is the median value for that HLA allele. The dotted line is the median value of the total cohort.</p

Association between CD57 expression on CD4 T cells and disease progression.

<p><b>A.</b> Comparison of CD57 expression on CD4 T cells between progression groups. <b>B.</b> Correlation between log viral load (LVL) and CD57 expression on CD4 T cells. <b>C.</b> Correlation between CD4% and expression of CD57 on CD4 T cells.</p

Patient cohort characteristics.

a<p>Log viral load.</p>b<p>H = Hispanic; AA = African American.</p

Patient cohort characteristics.

a<p>Log viral load.</p>b<p>H = Hispanic; AA = African American; M = Male; F = Female; Race was not available for 1 subject in the NS group and 2 subjects in the SS group.</p><p>The numbers in parentheses represent 95% confidence intervals.</p

Association between Gag specific responses and disease progression.

<p>The magnitude of the total observed Gag specific responses (the sum of all the epitope- specific responses) is compared between the two groups in panel A. Correlations between LVL and the magnitude of the total observed Gag response are displayed for both progression groups in panels B and C.</p