Publications

HIV infection can result in depletion of total CD4(+) T cells and naive CD8(+) T cells, and in the generation of dysfunctional effector CD8(+) T cells. In this study, we show that naive CD8(+) T cells in subjects with progressive HIV disease express low levels of CD8α and CD8β chains. Such naive CD8(low) T cells display broad signaling defects across the T-cell receptor complex, and their appearance correlates with generalized up-regulation of major histocompatibility complex class I (MHC-I) antigens on peripheral blood mononuclear cells (PBMCs). To explore a causal link between increased MHC-I up-regulation and the generation of naive CD8(low) T cells, we used the humanized SCID-hu Thy/Liv mouse model to show that HIV infection of the thymus and interferon α (IFNα) treatment alone result in MHC-I up-regulation and in the generation of dysfunctional CD3(high)CD8(+)CD4(-) single-positive 8 (SP8) thymocytes with low expression of CD8. We suggest that dysfunctional naive CD8(low) T cells are generated as a result of IFNα-mediated up-regulation of MHC-I on stromal cells in the thymus and antigen-presenting cells in the periphery, and that dysfunction in this naive compartment contributes to the immunodeficiency of HIV disease. This study is registered at www.clinicaltrials.gov as NCT00187512.

OBJECTIVE

To evaluate the association between treatment of HIV-tuberculosis (TB) coinfection and primary virologic failure among children initiating antiretroviral therapy in South Africa.

DESIGN

We performed a retrospective cohort study of 1029 children initiating antiretroviral therapy at two medical centers in KwaZulu Natal, South Africa, a region of very high TB incidence.

METHODS

Data were extracted from electronic medical records and charts and the impact of TB cotreatment on viral suppression at 6 and 12 months was assessed using logistic regression.

RESULTS

The overall rate of virologic suppression (<400 HIV RNA copies/ml) was 85% at 6 months and 87% at 12 months. Children who received concurrent treatment for TB had a significantly lower rate of virologic suppression at 6 months (79 vs. 88%; P = 0.003). Those who received nonnucleoside reverse transcriptase inhibitor-based HAART had similar rates of viral suppression regardless of whether they received concurrent TB therapy. In contrast, children who received protease inhibitor-based HAART had significantly lower viral suppression rates at both 6 and 12 months if treated concurrently for TB (P = 0.02 and 0.03). Multivariate logistic regression revealed that age at initiation, protease inhibitor therapy, and TB coinfection were each independently associated with primary virologic failure.

CONCLUSION

Concurrent treatment for TB is associated with lower rates of viral suppression among children receiving protease inhibitor-based HAART, but not among those receiving nonnucleoside reverse transcriptase inhibitor-based HAART. Guidelines for the care of young HIV-TB coinfected infants should be continually evaluated, as protease inhibitor-based antiviral therapy may not provide optimal viral suppression in this population.

OBJECTIVE

To examine the impact of physician counseling on perceived risks, benefits, and likelihood of use of anxiolytic pharmacotherapy during pregnancy among women with a history of anxiety.

METHOD

We surveyed 96 nonpregnant women, aged 21-45 years, with panic disorder and/or generalized anxiety disorder (DSM-IV criteria) recruited by their family physicians to participate in an anxiety treatment trial from 7 primary care practices in Pittsburgh, Pennsylvania. Trained research assistants telephoned study participants to assess sociodemographics, psychiatric history, comorbidities, and anxiety severity. Respondents were asked to assess risks, benefits, and likelihood of taking a prescribed anxiolytic during pregnancy using 3 Likert scales at baseline. Respondents were then asked to indicate whether their perceptions would change with (1) a US Food and Drug Administration (FDA) warning reporting a 5% chance of birth defects with use and (2) physician counseling that the medication was safe during pregnancy despite the warning. Data were collected from January 1, 2005, through December 30, 2007.

RESULTS

In this study, 46% (44/96) of respondents had generalized anxiety disorder, 14% (14/96) had panic disorder, and 40% (38/96) had both generalized anxiety disorder and panic disorder. The mean baseline Hamilton Anxiety Rating Scale score was 25.6 (SD = 8.4). Respondents were less likely to perceive risk if counseled by their primary care physicians that medication use was safe despite FDA warning. They also saw more benefit in use and reported being more likely to take anxiolytic medications during pregnancy if counseled that doing so was safe. Age, ethnicity, and severity of anxiety did not modify the effect of physician counseling. However, college educated women were less likely to be reassured by primary care physician counseling (P = .05) that anxiolytic use during pregnancy was safe.

CONCLUSIONS

Women with anxiety disorders are often hesitant to use anxiolytic medications during pregnancy. Physician counseling may change some women's perceptions of risk and decisions regarding use during pregnancy.

TRIAL REGISTRATION

Clinicaltrials.gov Identifier: NCT00158327.