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The article presents a study on the challenges and lessons learned in the A5207 study on nevirapine (NVP) resistance in mothers conducted in eight sites located in resource-limited settings (RLS). It states that survey data and semi-structured interviews during the site preparation were assessed. Results show that the sites addressed challenges in four target areas including regulatory affairs, pharmacy services, and clinical research practices.

Background: An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG) A5187 was a phase I/II, randomized, placebocontrolled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00- VP) in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099) Methods: Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation. Results: Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log10 HIV-1 RNA copies/mL, respectively. Conclusions: The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP) was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of discontinuing treatment in this group. Trial Registration: Clinicaltrials.gov NCT00125099. [ABSTRACT FROM AUTHOR]

Background. We have attempted to identify factors associated with T cell reconstitution in response to highly active antiretroviral therapy. Methods. In a prospective, multicenter cohort study, we compared clinical, immune, and viral responses to an initial antiretroviral regimen in older (≥45 years old) versus younger (18-30 years old) human immunodeficiency virus type 1-infected subjects. Multivariable linear-regression models identified independent factors associated with changes in T cell counts. Results. Older subjects had smaller increases in naive T cells but greater T cell receptor-excision circle DNA content after 48 weeks, despite similar virologic responses and comparable reductions in immune activation. Changes in T cell counts were associated with plasma interleukin (IL)-7 levels in subjects with low thymic scores, whereas first-phase T cell increases (perhaps mediated by redistribution to the circulation of tissue-associated lymphocytes) were associated with reductions in immune activation in subjects with high thymic scores. Reductions in immune activation were associated with reductions in spontaneous lymphocyte apoptosis. Conclusions. Distinct processes may underlie T cell restoration, according to estimated thymic volumes. IL- 7-mediated peripheral expansion may drive T cell restoration in persons with low thymic volume, whereas therapy- associated reversal of immune reactivation may drive T cell losses and their restoration in persons with larger thymic volume. [ABSTRACT FROM AUTHOR]