Publications

CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.

BACKGROUND

Several host-encoded antiviral factors suppress HIV-1 replication in a cell-autonomous fashion in vitro. The relevance of these defenses to the control of HIV-1 in vivo remains to be elucidated. We hypothesized that cellular restriction of HIV-1 replication plays a significant role in the observed suppression of HIV-1 in "elite controllers", individuals who maintain undetectable levels of viremia in the absence of antiretroviral therapy (ART). We comprehensively compared the expression levels of 34 host restriction factors and cellular activation levels in CD4+ T cells and sorted T cell subsets between elite controllers, HIV-1-infected (untreated) non-controllers, ART-suppressed, and uninfected individuals.

RESULTS

Expression of schlafen 11, a codon usage-based inhibitor of HIV-1 protein synthesis, was significantly elevated in CD4+ T cells from elite controllers as compared to both non-controllers (p = 0.048) and ART-suppressed individuals (p = 0.024), with this effect most apparent in central memory CD4+ T cells. Schlafen 11 expression levels were comparable between controllers and uninfected individuals. Cumulative restriction factor expression was positively correlated with CD4+ T cell activation (r² = 0.597, p < 0.0001), viral load (r² = 0.34, p = 0.015), and expression of ISG15 (r² = 0.73, p < 0.0001), a marker of interferon exposure. APOBEC3C, APOBEC3D, CTR9, TRIM26, and TRIM32 were elevated in elite controllers with respect to ART-suppressed individuals, while levels were comparable to uninfected individuals and non-controllers.

CONCLUSIONS

Host restriction factor expression typically scales with cellular activation levels. However, the elevated mRNA and protein expression of schlafen 11, despite low activation and viral load, violates the global pattern and may be a signature characteristic of HIV-1 elite control.

In 2012, new publications in the Journal described both the predictive value of the new IFN-γ release assays for diagnosis of latent tuberculosis (TB), but also provided evidence that these new tests cannot be interpreted simply as positive or negative, as initially hoped. Surgical masks can reduce transmission of TB infection, but other measures such as state-wide implementation of targeted testing and treatment of latent TB or active case finding require substantial and sustained effort to successfully reduce TB morbidity and mortality. A quasiexperimental study revealed that a package of social interventions could substantially reduce risk of TB disease in heavily exposed (and infected) children in the preantibiotic era. A study in a high-TB burden setting suggested that a new rapid drug-susceptibility test for TB may be more practical for implementation than traditional culture-based phenotypic tests. And two studies of TB vaccines revealed that currently used bacillus Calmette-Guérin strains vary in their ability to affect correlates of immunogenicity, whereas a new candidate vaccine, MVA85A, was safe and immunogenic in adults. Studies of nontuberculous mycobacteria (NTM) described a rapid rise in the prevalence and spatial clustering of NTM in the United States over the past decade. Although risk factors for pulmonary NTM such as advanced age and low BMI are known, the mechanisms underlying infection and disease remain mysterious. Four studies of therapy of NTM disease highlighted the pressing need for well-designed international randomized controlled trials to improve our management of NTM disease.

OBJECTIVE

To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization.

RESEARCH DESIGN AND METHODS

The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified. The effect of diabetes with and without insulin use on the rate of first fall-related injury hospitalization was assessed using proportional hazards models.

RESULTS

At baseline, 719 participants had diabetes, and 117 of them were using insulin. Of the 293 participants who were hospitalized for a fall-related injury, 71 had diabetes, and 16 were using insulin. Diabetes was associated with a higher rate of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12-1.95]) in models adjusted for age, race, sex, BMI, and education. In those participants using insulin, compared with participants without diabetes, the HR was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as fainting in the past year, standing balance score, cystatin C level, and number of prescription medications, accounted for some of the increased risk associated with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]). Among participants with diabetes, a history of falling, poor standing balance score, and A1C level ≥8% were risk factors for an injurious fall requiring hospitalization.

CONCLUSIONS

Older adults with diabetes, in particular those using insulin, are at greater risk of an injurious fall requiring hospitalization than those without diabetes. Among those with diabetes, poor glycemic control may increase the risk of an injurious fall.