Routine monitoring of blood lymphocyte subpopulations in people with HIV infection

In patients with HIV infection not receiving antiretroviral therapy (ART), the blood CD4+ T cell count or proportion (CD4+ T cells as a percentage of total lymphocytes) should be monitored because they relate to the extent of HIV disease and guide the use of prophylactic antimicrobial therapy to prevent opportunistic infections. However, there is limited value in regularly monitoring CD4+ T cell counts in patients who achieve persistent suppression of HIV replication (HIV RNA <200 copies/mL) and a CD4+ T cell count >300/mL once ART is established, unless non-HIV related causes of CD4+ T cell depletion, such as radiotherapy or immunosuppressive therapy, are introduced (1). Guidelines on using CD4+ T cell counts to monitor people with HIV infection are provided at http://arv.ashm.org.au/plasma-hiv-1-rna-viral-load-and-cd4-count-monitoring/

Assessing T cell CD4/8 ratios may have clinical utility in HIV-infected individuals, particularly those with suppressed HIV replication on ART, because they reflect the effect of both the number of CD4+ T cells and CD8+ T cell activation and expansion related to reactivation of infections with viruses such as cytomegalovirus, which has been linked to an increased risk of HIV co-morbidities (2). In addition, examination of other lymphocyte subpopulations may provide additional information about HIV disease progression or immune reconstitution on ART. For example, increased proportions of activated T cells are a strong predictor of HIV disease progression independent of CD4+ T cell counts (3,4) and may predict CD4+ T cell recovery on ART (5). Also, the number or proportion of naïve CD4+ T cells or recent thymic emigrants in patients receiving ART are an indicator of immune reconstitution related to production of new CD4+ T cells (6,7). Finally, assessing memory B cells may provide information about the cause of defects of antibody production sometimes encountered in patients receiving ART (8). However, the information obtained from assessing these other lymphocyte subpopulations is not routinely needed to make treatment decisions

The methods used to assess lymphocyte subpopulations in the blood of patients with HIV infection are summarised in Table 1.

Table 1. Methods used to detect and enumerate lymphocyte subsets

Cell type

Lymphocyte markers

Method

CD4+ (‘helper’) T cell

CD8+ (‘cytotoxic’) T cell

Naïve CD4+ or CD8+ T cell

Central memory CD4+ or CD8+ T cell

Effector CD4+ or CD8+ T cell

Effector memory CD4+ or CD8+ T cell

CD4+

CD8+

CCR7+, CD45RA+

CCR7+, CD45RA-

CCR7-, CD45RA+

CCR7-, CD45RA-

Flow cytometry

Activated CD4+ or CD8+ T cell

CD38+, HLA-DR+

Flow cytometry

Recent thymic emigrant T cell

TRECs

PCR

B cell

Memory B cell

CD19+

CD27+

Flow cytometry

TRECs: T cell receptor excision circles      PCR: Polymerase chain reaction