Persistence of viral reservoirs in multiple tissues after antiretroviral therapy suppression in a macaque RT-SHIV model

Although antiretroviral therapy (ART) can suppress HIV-1 replication sufficiently to eliminate measurable plasma viremia, infected cells remain and ensure viral recrudescence after discontinuation of ART. We used a macaque model of HIV-1/AIDS to evaluate the location of infected cells during ART. Twelve macaques were infected with RT-SHIVmne, a SIV containing HIV-1 reverse transcriptase, conferring sensitivity to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten to fourteen weeks post-infection, 6 animals were treated with 3 or 4 antiretroviral drugs for 17-20 weeks; 6 control animals remained untreated. Viral DNA (vDNA) and RNA (vRNA) were measured in peripheral blood mononuclear cells (PBMC) and at necropsy in multiple tissues by quantitative PCR and RT-PCR. The majority of virally infected cells were located in lymphoid tissues with variable levels in the gastrointestinal tract of both treated and untreated animals. Tissue viral DNA levels correlated with week 1 plasma viremia, suggesting that tissues that harbor proviral DNA are established within the first week of infection. PBMC vDNA levels did not correlate with plasma viremia or tissue levels of vDNA. vRNA levels were high in lymphoid and gastrointestinal tissues of the untreated animals; animals on ART had little vRNA expressed in tissues and virus could not be cultured from lymph node resting CD4+ cells after 17-20 weeks on ART, indicating little or no ongoing viral replication. Strategies for eradication of HIV-1 will need to target residual virus in ART suppressed individuals, which may not be accurately reflected by frequencies of infected cells in blood. © 2013 Kline et al

Changes in Hard and Soft News Content of Major Television Network Newscasts in the Middle 1980s

In the last decade, there has been a tendency for the three major television network newscasts to increase the amount of soft news. Soft news is defined as any story that focuses on a human interest topic, feature, or non-policy event. A content analysis of the Vanderbilt Television News Abstracts comparing 1973 through 1976 with 1983 through 1986 shows all three networks did slightly increase the amount of soft news in the middle 1980s. It was, however, a small increase

Impaired Caregiving, Trauma Exposure, and Psychosocial Functioning in a National Sample of Children and Adolescents.

Impairments in Caregiving (ICG) secondary to mental illness and substance use have been linked to adverse outcomes in children. Little is known, however, about whether outcomes vary by type of ICG, exposure to co-occurring traumas, or mechanisms of maladaptive outcomes. Clinic-referred youth age 7-18 years (n = 3988) were compared on ICG history, demographics, trauma history, and mental health symptoms. Child trauma exposure was tested as a mediator of ICG and child symptoms. Youth with ICG were at heightened risk for trauma exposure, PTSD, internalizing symptoms, total behavioral problems, and attachment problems, particularly youth with multiple types of ICG. Effect sizes were moderate to large for PTSD, internalizing symptoms, and total behavioral problems. Number of trauma types mediated the relationship between ICG and child symptoms. ICG was related to trauma exposure within and outside the family context. Understanding these links has important implications for interrupting intergenerational trauma and psychopathology

Impaired Caregiving, Trauma Exposure, and Psychosocial Functioning in a National Sample of Children and Adolescents

Impairments in Caregiving (ICG) secondary to mental illness and substance use have been linked to adverse outcomes in children. Little is known, however, about whether outcomes vary by type of ICG, exposure to co-occurring traumas, or mechanisms of maladaptive outcomes. Clinic-referred youth age 7-18 years (n = 3988) were compared on ICG history, demographics, trauma history, and mental health symptoms. Child trauma exposure was tested as a mediator of ICG and child symptoms. Youth with ICG were at heightened risk for trauma exposure, PTSD, internalizing symptoms, total behavioral problems, and attachment problems, particularly youth with multiple types of ICG. Effect sizes were moderate to large for PTSD, internalizing symptoms, and total behavioral problems. Number of trauma types mediated the relationship between ICG and child symptoms. ICG was related to trauma exposure within and outside the family context. Understanding these links has important implications for interrupting intergenerational trauma and psychopathology

Lymphoid tissue viral DNA at necropsy is correlated with week 1 plasma viremia levels.

<p>(A) The ratio of <i>gag</i> copies per 10⁶ CCR5 copies for each tissue of the untreated RT-SHIV-infected macaques. The average of each qPCR reaction was used for the graph. In addition, the week 1 plasma viral load was included for each animal. Asterisks (*) denote samples that were not collected or in which no significant CCR5 DNA were measured. (B) The amount of <i>gag</i> vDNA detected in each of the lymphoid tissues for each animal was plotted against the week 1 plasma viremia level. Statistics determined a Spearman rank-order correlation of 0.996 with p value of < 0.0001.</p

Plasma viremia was measured in all twelve macaques by qRT-PCR of RT-SHIV <i>gag</i> RNA.

<p>Animals were infected at week 0 and were (A) untreated or (B) treated with 3 or 4 antiretroviral drugs. Animals treated with 3 drugs (TFV, FTC, EFV) are denoted by closed symbols and treatment was initiated at week 10, denoted by the solid arrow. The animals treated with 4 drugs (TFV, FTC, EFV, and L-870812) are denoted by open symbols and treatment was initiated at week 13 (GV08 and GN19) or week 14 (GG45 and GV40), denoted by the open arrow. Treatment was continued daily until necropsy (week 30 or 31). The limit of detection of the assay was 30 vRNA copies/ml plasma.</p

The ratio of RT-SHIV <i>gag</i> RNA copies per 10⁶ macaque CD4 RNA copies were measured in PBMC isolated at week 1 or 2 and 28 or 30 post-infection from each of the untreated and treated macaques (black bars).

<p>The amount of RT-SHIV gag RNA in the plasma is also plotted for each animal at each time point (white bars). Asterisks (*) denote plasma viremia levels below the limit of detection (<30 copies/ml).</p