Pandemic-related health behavior: repeat episodes of influenza-like illness related to the 2009 H1N1 influenza pandemic.

The Houston Health Department (HHD) in Texas tracks influenza-like illness (ILI) in the community through its Influenza Sentinel Surveillance Program, which began in 2008. After the influenza A(H1N1) pandemic (pH1N1) in 2009, investigators sought to assess the feasibility of this program as a non-traditional data source for tracking and monitoring care-seeking activities. Through the process of characterizing and describing patients who had 'return visits', or who were considered the heaviest ILI-related care-utilizers, the investigators sought to understand the strengths and limitations of this data source. Data used for this study were obtained from a multispecialty clinic in Houston, Texas between August 2008 and January 2011 across three phases: pre-pH1N1, pH1N1, and post-pH1N1. The data, which comprised of 4047 patient visits, yielded 150 return visits. We found an increase in the number of visits for ILI and proportion of return visits during the pandemic phase (pH1N1), as well as differences in the likelihood of a return visit between genders and age groups. More broadly, the findings of this study provide important considerations for future research and expose important gaps in using surveillance data to assess sick-role behaviors.

Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy.

Cytotoxic T lymphocytes (CTLs) are an important defense against human immunodeficiency virus (HIV) type 1 but ultimately fail to control infection. To determine whether more efficient sustained immunity is induced by suppressing replication, the evolution of T cell phenotypes and HIV-specific CD8+ lymphocytes was prospectively investigated in 41 patients initiating combination therapy. Suppression of viremia to <200 copies/mL was associated with increases in naive cells (CD45RA+62L+) and declines in activated T cells (CD95+ cell counts and CD38+ HLA-DR+). HIV-specific tetramer-staining CD8+ T cells were detected in 6 of 10 HLA-A*0201-positive persons, which declined in 5 with treatment. CTL precursor frequencies were markedly consistent before and after treatment. Eight (72%) of 11 recognized > or =1 immunodominant epitope, representing either a new or an increased CTL response after treatment. Thus, activated CD8+ T cells, including those recognizing immunodominant epitopes, decline with combination therapy. However, the overall level of antigen-specific cells that are capable of differentiating into effectors remains stable, and the recognition of new epitopes may occur.

Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection.

T-cell responses were evaluated prospectively in 41 patients with acute human immunodeficiency virus type 1 (HIV-1) infection (30 untreated and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults. By 6-12 months, treated patients had significantly greater median Candida and tetanus lymphoproliferative responses (stimulation index [SI], 76 and 55, respectively) than did untreated patients (SI, 7 and 6, P=.02 and.001, respectively), and the responses of treated patients surpassed those of uninfected adults (SI, 19 and 32, P= .002 and .101, respectively). Unlike the patients in the untreated group, the patients in the treated group mounted a 6-fold increased HIV-1 p24 response (SI increase, 1.0 to 5.7, P= .01) within 3 months. HIV-1-specific cytotoxicity remained detectable in most treated patients. Thus, combination therapy administered within 3-4 months of infection was associated with improved T-cell memory responses that were distinct from those of untreated patients. The amplified HIV-1-specific T-cell responses may help maintain cytotoxic activities.

Cellular immunity and target cell susceptibility in persons with repeated HIV-1 exposure.

We prospectively studied 37 HIV-1 uninfected persons engaging in repeated high risk sexual activity with an HIV-1 infected partner, as well as 18 of their infected partners. Only one subject (3%) demonstrated the homozygous 32-bp deletion delta32delta32 of the HIV-1 co-receptor CCR5. CD4+ cells from all high risk subjects except the delta32delta32 CCR5 homozygote were susceptible in vitro to both CCR5-dependent and CXCR4-dependent HIV-1 strains. Median HIV-1 plasma RNA levels of the infected partners were not significantly different from levels of matched infected controls. Thirteen subjects demonstrated HIV-1 specific CTL at one or more visits, and these activities were more commonly observed in persons with the wild type CCR5 genotype. These results indicate that cellular immunity rather than inheritance of the delta32 CCR5 mutation accounts more often for persistently HIV-1-resistant cases.

Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: evidence for T cell immunity in the absence of inherited CCR5 coreceptor defects.

It has been hypothesized that protection against human immunodeficiency virus (HIV)-1 infection may result from either acquired host immunity, inheritance of a dysfunctional CCR5 HIV-1 coreceptor, or a low or attenuated virus inoculum. Thirty-seven HIV-1-uninfected persons engaging in repeated high-risk sexual activity with an HIV-1-infected partner were prospectively studied to determine the contribution of these factors in protecting against HIV-1 transmission. More than one-third (13/36) demonstrated HIV-1-specific cytotoxicity, and this activity significantly correlated with the wild type CCR5 genotype (P=.03). Only 1 subject (3%) demonstrated the homozygous CCR5 32-bp deletion (Delta32/Delta32). Median plasma HIV-1 RNA levels from 18 HIV-1-infected sex partners were not statistically different from those of matched infected control patients. These results indicate that inheritance of the Delta32 CCR5 mutation does not account for the majority of persistently HIV-1-resistant cases, and the presence of cellular immunity in these persons suggests either undetected infection or protective immunity.