Profile of men identified as cases and controls in three respective scenarios of primary prevention, cohort study and clinical trial.

<p>CI: Confidence Interval.</p

<em>Mycobacterium tuberculosis</em> Complex Enhances Susceptibility of CD4 T Cells to HIV through a TLR2-Mediated Pathway

<div><p>Among HIV-infected individuals, co-infection with <em>Mycobacterium tuberculosis</em> is associated with faster progression to AIDS. We investigated the hypothesis that <em>M. bovis</em> BCG and <em>M. tuberculosis</em> (Mtb complex) could enhance susceptibility of CD4+ cells to HIV infection. Peripheral blood mononuclear cells (PBMCs) collected from healthy donors were stimulated with <em>M. bovis</em> BCG, <em>M. tuberculosis</em> CDC1551 and <em>M. smegmatis</em> MC²155, and stimulated CD4+ cells were infected with R5-and X4-tropic single replication-competent pseudovirus. CD4+ cells stimulated with Mtb complex showed enhanced infection with R5- and X4-tropic HIV, compared to unstimulated cells or cells stimulated with <em>M. smegmatis</em> (p<0.01). Treatment with TLR2 siRNA reversed the increased susceptibility of CD4+ cells with R5- and X4-tropic virus induced by Mtb complex. These findings suggest that TB infection and/or BCG vaccination may be a risk factor for HIV acquisition.</p> </div

Univariate analysis of Predictors of Retention in three modeled scenarios.

<p>Univariate analysis of Predictors of Retention in three modeled scenarios.</p

Silencing of TLR2 expression attenuates the increased susceptibility to HIV.

<p>Expression of TLR2 increases at the transcription level in cells stimulated with <i>M. bovis</i> BCG when compared to cells stimulated with <i>M. smegmatis</i> (A). The expression levels of TLR4 and TLR9 do not show a significant difference in cells stimulated with different strains of mycobacteria as evidenced by RT-PCR. Comparison of HIV infectivity of CD4+ cells transfected with scrambled siRNA and subsequently stimulated with <i>M. bovis</i> BCG to CD4+ cells transfected with TLR2 siRNA and subsequently stimulated with <i>M. bovis</i> BCG (B) **p<0.005. TLR2 expression on CD4+ cells after stimulation with <i>M. bovis</i> BCG, <i>M. tuberculosis</i>, and <i>M. smegmatis</i> compared to TLR2 expression on CD4+ cells transfected with TLR2 siRNA and subsequently stimulated with <i>M. bovis</i> BCG (C). The expression showed similar trends for the four samples tested. Dot plots comparing the percentage of surface expression of TLR2 on unstimulated CD4+ cells and CD4+ cells stimulated with <i>M. bovis</i> BCG, <i>M. tuberculosis</i> (CDC1551), <i>M. smegmatis</i> (MC²155), and CD4+ cells transfected with TLR2 siRNA and subsequently stimulated with <i>M. bovis</i> BCG (D).</p

<i>M. tuberculosis</i> complex increases susceptibility to HIV infectivity.

<p>The percentage of unstimulated CD4+ cells and CD4+ cells stimulated with PHA (50 µg/ml), <i>M. bovis</i> BCG (Copehnhagen), <i>M. tuberculosis</i> (CDC1551), <i>M. smegmatis</i> (MC²155) from individual subjects infected with X4-tropic pseudovirus (A) or R5-tropic pseudovirus (B). Results from individual donors are color-coded. Statistical analysis was performed using student T test (** p<0.005). Flow cytometry analysis of the representative CD4+ cells after infection with GFP-expressing pseudovirus (C).</p

Differential susceptibility to HIV infection is not dependent on increased expression of the immune activation markers CD38 and HLA DR.

<p>Cells stimulated with different antigens are activated to a similar extent as evidenced by expression of immune activation marker CD38 (A). Dot plots from unstimulated CD4+ cells and CD4+ cells stimulated with PHA (150 g/ml), <i>M. bovis</i> BCG (Copenhagen) and <i>M. tuberculosis</i> (CDC1551) depicting the expression of immune activation marker CD38 (B). Cells stimulated with <i>M. bovis</i> BCG (Copenhagen) and <i>M. tuberculosis</i> (CDC1551) show lower expression of MHC II molecule HLA DR when compared to cells stimulated with <i>M. smegmatis</i> MC²155 (C) *p<0.05.</p

Predictors of retention in the modeled scenario of primary prevention (1a), cohort study (1b) and clinical trial (1c).

<p>Predictors of retention in the modeled scenario of primary prevention (1a), cohort study (1b) and clinical trial (1c).</p

Showing the study participant characteristics in step 1 and step 2 analysis

<p>Showing the study participant characteristics in step 1 and step 2 analysis</p

Factors associated with failure to change from inconsistent condom use to ‘positive’ condom use behavior among male STD patients.

<p>^‡Others include unmarried, divorced, widower and separated.</p><p>GUD: Genital ulcer disease, GD: Genital discharge</p><p>* Significant at p value < 0.05,</p><p>** Significant at p value < 0.01</p><p>¹ Hijra is local term for éunuch</p><p>Factors associated with failure to change from inconsistent condom use to ‘positive’ condom use behavior among male STD patients.</p

Cox professional hazards analysis showing risk factors and hazards of inconsistent condom use during follow-up of two years among male patients attending STD clinics.

<p>^‡ Buddhist, Christian, Muslims and Others</p><p>^$$ Widowed, divorced and separated.</p><p>NA: Not applicable</p><p>* Significant at p value < 0.05,</p><p>** Significant at p value < 0.01</p><p>Cox professional hazards analysis showing risk factors and hazards of inconsistent condom use during follow-up of two years among male patients attending STD clinics.</p