Domestic Violence Recidivism: Restorative Justice Intervention Programs for First-Time Domestic Violence Offenders

Domestic violence impacts millions of Americans annually and, in spite of the use of rehabilitative programs, recidivism in domestic violence continues to be more likely than in any other offense. To date, batterer intervention programs (BIPs) have not proven to be consistently impactful in reducing recidivism in cases of domestic violence. The purpose of this quasi-experimental, quantitative study was to examine differences in recidivism for first-time male domestic violence offenders who have participated in a BIP and a more recently developed alternative: victim-offender mediation (VOM). The theories of restorative justice and reintegrative shaming frame this study to determine if offenders take accountability for their actions and face the victim in mediation, there can be a reduction in recidivism. Archival data from records of first-time male, domestic violence offenders, between the ages of 18 and 30, who participated in either a VOM or BIP in a county in the Midwest were examined for recidivism 24-months postintervention, and analyzed with an ANCOVA analysis while controlling for age. The findings revealed no significant difference in recidivism for first-time male offenders 24-months post participation in a BIP or a VOM intervention while controlling for age F (1,109) =.081, p = .777. The findings provide support for the notion that restorative justice interventions may be an additional intervention used in cases of domestic violence deemed appropriate for the intervention. The findings from this study can add to the body of research examining interventions to address the high recidivism in cases of domestic violence, which impacts victims, offenders, and communities

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses

Ajuts: R01/R56 NIH Grant AI-52779 (GDT), NIH F31 Fellowship (1F31AI106519-01)(TLP), Center for AIDS Research (P30 AI 64518) i Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, grant number UM1-AI100645-01 (AM)Abstract.Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called "beneficial" regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control

Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called “beneficial” regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses

Ajuts: R01/R56 NIH Grant AI-52779 (GDT), NIH F31 Fellowship (1F31AI106519-01)(TLP), Center for AIDS Research (P30 AI 64518) i Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, grant number UM1-AI100645-01 (AM)Abstract.Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called "beneficial" regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control

Vaccines based on full-length protein immunogens elicit subdominant responses to beneficial regions and / or conserved elements within the HIV proteome.

<p><b>A.</b> Post-vaccination, pre-infection CD8+ T cell responses to overlapping peptides spanning the MRK Ad5 Gag/Pol/Nef immunogen determined by IFN-γ Elispot assay in 13 HVTN 502 participants (dark blue bars) (4 weeks post-second vaccination). Responses to beneficial regions and Gag conserved elements within the immunogen are indicated by magenta and turquoise bars respectively. <b>B.</b> Pre- and post-vaccination responses to beneficial and non-beneficial regions within Gag determined by IFN-γ Elispot assay in 9 HIV-positive subjects after therapeutic vaccination with MVA.HIVA.</p

CD8+ T cell responses to PTE peptides based on to the entire HIV proteome were measured in HIV-positive HVTN participants (502—vaccinees, black closed circles; placebos, black open circles) and (503—vaccinees, grey closed circles; placebos, grey open circles) at week 5 post-infection by intracellular staining for IFN-γ.

<p><b>A.</b><b>B.</b> Correlation between CD8+ T cell inhibition (CD8+/CD4+ cell ratio = 2:1) of a clade-matched virus and magnitude of CD8+ T cell response to the entire HIV proteome, colour-coded as indicated in A. Five subjects are not shown in B, due to lack of viral inhibition data for the 2:1 ratio.</p

Multivariate linear regression models to investigate associations between beneficial responses, entropy, HLA alleles and % inhibition (dependent variable).

<p>In each model, magnitude = total beneficial response (sum of responses to beneficial peptide pools)</p><p>Ratio of protective / total response = total beneficial response / total proteome response (both defined as IFN-γ+ cells/million CD8+ T cells)</p><p>* HLA-B*27, B*51, B*5701, B*5801, B*81</p><p>^§ HLA-B*35 (Py), HLA-B*53</p><p>Multivariate linear regression models to investigate associations between beneficial responses, entropy, HLA alleles and % inhibition (dependent variable).</p

Distribution of responses to Gag peptides in HIV-positive MVA.HIVA vaccinees.

<p>Distribution of responses to Gag peptides in HIV-positive MVA.HIVA vaccinees.</p

CD8+ T cell inhibitory activity and targeting of beneficial regions and conserved elements within the HIV proteome.

<p>CD8+ T cell responses to peptides based on (<b>A</b>) clade-specific ‘beneficial’ regions and (<b>B</b>) Gag ‘conserved elements’ were measured by IFN-γ Elispot assays. Net responses (background subtracted) are shown; values for negative controls were median (IQR)– 10 (0–15) SFU/million CD8+ T cells. Horizontal lines indicate median values. HVTN vaccinees and placebos are shown as closed and open symbols respectively in <b>A</b>. In <b>B</b>, HVTN subjects are grouped together and represented as follows: HVTN 502—vaccinees, black closed circles, placebos, black open circles; HVTN 503—vaccinees, grey closed circles, placebos, grey open circles. VC are shown as triangles in <b>A & B</b>. Six HVTN 503 subjects were excluded as viral subtype data were not confirmed at the time of the analysis. One VC subject was excluded as no sample was available for Elispot assay. <b>C.</b> Correlation between CD8+ T cell inhibition of a clade-matched virus (CD8+/CD4+ cell ratio = 2:1) and magnitude of CD8+ T cell responses to beneficial peptides (summed) in 26 HVTN subjects. <b>D.</b> The analysis was repeated after removal of subjects with protective HLA class I alleles and (<b>E</b>) with short-term cell lines expanded from CD8+ T cells recovered from Elispot assays in 15 subjects that were then tested with individual peptides from the pools which elicited a response in the ex vivo Elispot assay. <b>For C-F</b>: closed circles—502 and 503 vaccinees; open circles—502 and 503 placebos. <b>F.</b> Correlation between CD8+ T cell inhibition (2:1 ratio) of a clade-matched virus and magnitude of CD8+ T cell responses to conserved elements peptides in 27 HVTN subjects (left panel—sum of all CE peptides, middle—CE pool A, right—CE pool B).</p

Characteristics of HVTN 502 and 503 trial participants.

<p>Data shown are median values (interquartile range) unless otherwise indicated.</p><p>* At time of sampling</p><p>^§ HLA-B*27, B51, B*5701/03, B*5801 and B*8101</p><p>Characteristics of HVTN 502 and 503 trial participants.</p