Poor HIV-related Outcomes Research Articles

The impact of community-based integrated HIV and sexual and reproductive health services for youth on population-level HIV viral load and sexually transmitted infections in Zimbabwe: protocol for the CHIEDZA cluster-randomised trial.

Youth have poorer HIV-related outcomes when compared to other age-groups. We describe the protocol for a cluster randomised trial (CRT) to evaluate the effectiveness of community-based, integrated HIV and sexual and reproductive health services for youth on HIV outcomes. The CHIEDZA trial is being conducted in three provinces in Zimbabwe, each with eight geographically demarcated areas (clusters) (total 24 clusters) randomised 1:1 to standard of care (existing health services) or to the intervention. The intervention comprises community-based delivery of HIV services including testing, antiretroviral therapy, treatment monitoring and adherence support as well as family planning, syndromic management of sexually transmitted infections (STIs), menstrual health management, condoms and HIV prevention and general health counselling. Youth aged 16-24 years living within intervention clusters are eligible to access CHIEDZA services. A CRT of STI screening (chlamydia, gonorrhoea and trichomoniasis) is nested in two provinces (16 of 24 clusters). The intervention is delivered over a 30-month period by a multidisciplinary team trained and configured to provide high-quality, youth friendly services.Outcomes will be ascertained through a population-based survey of 18-24-year-olds. The primary outcome is HIV viral load <1000 copies/ml in those living with HIV and proportion who test positive for STIs (for the nested trial). A detailed process and cost evaluation of the trial will be conducted. The trial protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policy-making bodies. https://clinicaltrials.gov/: NCT03719521.

Differential Associations of Depressive Symptomology to HIV Care Engagement Among Young Black Sexual Minority Men with HIV (YBSMM+) in the US South: A Multi-Group Analysis of Mood, Intimate Partner Violence, and Alcohol Use.

Young Black Sexual Minority Men with HIV (YBSMM+) in the US South encounter multiple socio-structural challenges that contribute to disproportionately poor HIV-related outcomes across the care continuum. Depression, anxiety, intimate partner violence (IPV), and alcohol use are prominent factors that negatively impact engagement with HIV care. Syndemic theory posits that these multiple factors interact synergistically to promote poor outcomes; however, depression itself is highly heterogeneous in presentation, which may pose issues when examining associations to HIV care engagement. This study sought to better understand the associations of specific depressive symptomology subtypes, generalized anxiety, experienced IPV, and alcohol use on HIV care engagement for YBSMM+. Results showed that interpersonally oriented depressive symptomatology was associated with increased HIV care engagement among YBSMM + who abstained from alcohol. On the other hand, among YBSMM + who frequently binge drank, combined negative affect and somatic components of depressive symptomatology and frequency of IPV experiences were associated with decreased HIV care engagement while generalized anxiety was associated with increased HIV care engagement. The findings suggest that the negative affect and somatic components of depression may be particularly salient for HIV care engagement among YBSMM + who binge drink frequently. Developing targeted interventions that address these specific conditions while accounting for the nuances of mood-based symptomatology could improve intervention efforts geared towards improving HIV care engagement among YBSMM+.

Food insecurity and depressive symptoms among young people living with HIV in Eastern Zambia.

Background: Mental health problems are common among people living with HIV/AIDS and contribute to poor HIV-related outcomes, including AIDS-related mortality. We examined the association between severe food insecurity and depressive symptoms in young people living with HIV (YPLH) in Zambia. Methods: We sampled 120 youth living with HIV aged 18-21years in the Eastern Province of Zambia. Household food insecurity was measured using the Household Food Insecurity Access Scale (HFIAS). Mental health was assessed using the Children's Depression Inventory-Short Form. We fitted linear regression models to assess whether food insecurity is associated with depressive symptoms. Results: The mean age was 19years, and 63% were female. Overall, 43% were severely food insecure. After adjusting for sociodemographic variables and other confounders, severely food insecure participants were more likely to report depressive symptoms (β = 0.81, 95% Confidence Interval [CI] 0.07-1.55) and engagement in sex work (β = 1.78, 95% CI 0.32-3.25). Conclusion: Almost half of the sample reported severe food insecurity which was associated with depressive symptoms. Interventions aimed at improving food insecurity may have beneficial effects on mental health and HIV outcomes among young people living with HIV in resource-limited settings.

Poor HIV-Related Outcomes In Older Adults Newly Diagnosed with HIV: A Four-Year Retrospective Analysis from A Single Site in Asia.

In resources limited settings, HIV-related services are often targeted to younger key populations though increasing reports have found adults ≥50 years now account for among the highest increase in new HIV diagnosis. We assessed the proportion of new HIV infections among older adults (≥50 years) and compared their socio-demographics, risk behaviours and HIV-related outcomes to newly diagnosed younger adults (<50 years). This retrospective analysis included all new HIV diagnosis from 2016-2019 at University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using joinpoint regression analysis and characteristics between the older and younger adults were compared using χ2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups. From a total of 594 new HIV diagnosis between 2016-2019, 11.5% (N=68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians (p<0.001), acquired HIV via heterosexual contact (p=0.001), had late presentation to care (p=0.003), and multimorbidity (p<0.001). Immunological responses after 12 months on ART were comparable in both groups. Older adults had a higher probability of death compared to younger adults (aHR 1.81, 95% CI 1.02-3.23, p=0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, ART initiation and multimorbidity. Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.

The impact of community-based integrated HIV and sexual and reproductive health services for youth on population-level HIV viral load and sexually transmitted infections in Zimbabwe: protocol for the CHIEDZA cluster-randomised trial

Background: Youth have poorer HIV-related outcomes when compared to other age-groups. We describe the protocol for a cluster randomised trial (CRT) to evaluate the effectiveness of community-based, integrated HIV and sexual and reproductive health services for youth on HIV outcomes. Protocol: The CHIEDZA trial is being conducted in three provinces in Zimbabwe, each with eight geographically demarcated areas (clusters) (total 24 clusters) randomised 1:1 to standard of care (existing health services) or to the intervention. The intervention comprises community-based delivery of HIV services including testing, antiretroviral therapy, treatment monitoring and adherence support as well as family planning, syndromic management of sexually transmitted infections (STIs), menstrual health management, condoms and HIV prevention and general health counselling. Youth aged 16-24 years living within intervention clusters are eligible to access CHIEDZA services. A CRT of STI testing (chlamydia, gonorrhoea and trichomoniasis) is nested in two provinces (16 of 24 clusters). The intervention is delivered over a 30-month period by a multidisciplinary team trained and configured to provide high-quality, youth friendly services. Outcomes will be ascertained through a population-based survey of 18–24-year-olds. The primary outcome is HIV viral load &lt;1000 copies/ml in those living with HIV and proportion who test positive for STIs (for the nested trial). A detailed process and cost evaluation of the trial will be conducted. Ethics and Dissemination: The trial protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board and the London School of Hygiene &amp; Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policy-making bodies. Trial Registration https://clinicaltrials.gov/: NCT03719521

'I think they might just go to the doctor': qualitatively examining the (un)acceptability of newer HIV testing approaches among Vietnamese-born migrants in greater-Brisbane, Queensland, Australia.

This study used semi-structured interviews to examine the (un)acceptability, barriers and facilitators to newer HIV testing approaches (i.e. PITC, HIV RT and HIV ST) among Vietnamese-born migrants (n = 10) in greater-Brisbane, Queensland, Australia. Vietnamese-born migrants had mixed perspectives on the (un)acceptability of newer HIV testing approaches. PITC was largely viewed by participants as a facilitator to HIV testing for Vietnamese-born migrants. Likewise, HIV RT (undertaken by a doctor in a medical setting, as opposed to a trained community member in a community setting) was generally considered to facilitate HIV testing. HIV ST was largely not considered acceptable to Vietnamese-born migrants and they would prefer to go to a doctor for HIV testing. Several factors were identified that either facilitate or act as barriers to newer HIV testing approaches, including privacy; cost of (accessing) HIV testing; comfort and convenience; healthcare provider relationship; risk perception; symptoms; and technical and emotional support. There is a need to understand migrants' HIV testing preferences if poorer HIV-related outcomes are to be overcome. The findings from this study show a preference for doctor-centred HIV testing, due to enhanced privacy, accuracy and support.

Barriers and Facilitators Along the HIV Care Cascade Among Hospitalized Adolescents in Western Kenya

Background/Objective: There are 1.7 million adolescents living with HIV (ALHIV) globally, the majority of whom live in Eastern and Southern Africa. Despite increasing access to antiretroviral therapy (ART), ALHIV experience poorer HIV-related outcomes at each stage of the care cascade relative to other age groups. We sought to investigate barriers and facilitators experienced at each stage of the HIV “care cascade” – testing, linkage to care, retention in care, and adherence to and viral suppression on ART – among a cohort of hospitalized adolescents. &#x0D; &#x0D; Methods: This qualitative study used semi-structured interviews of hospitalized ALHIV and their caregivers to investigate if crucial delays occurred at each stage of the HIV care cascade. Interviews explored barriers and facilitators at each stage, and were guided by a framework that considered adolescent- or family-level factors, developmental and mental health needs, society-level, programmatic, and health system factors. Interviews were audio-recorded, transcribed and translated. Members of the study team independently coded each transcript after inter-coder reliability was established. &#x0D; &#x0D; Results: Hospitalized ALHIV experienced critical delays in care, most frequently at the stages of HIV diagnosis and ART adherence. Common barriers to testing related to lack of awareness around perinatal HIV and unknown maternal HIV status. Barriers to adherence were complex and heterogeneous. Common barriers included lack of HIV disclosure or problematic disclosure to the adolescent; intense stigma and challenges coming to terms with one’s HIV status; and issues related to ART side effects and tolerance. Facilitators to adherence included family supervision and support in ART taking, and HIV education and adherence counseling provided at the clinic. &#x0D; &#x0D; Conclusion and Policy Impact: Hospitalized adolescents experienced significant delays in care, most frequently at the stages of pediatric HIV diagnosis and ART adherence. Barriers to adherence are particularly complex. Interventions to address adolescent ART adherence are urgently needed.

The impact of China-to-US immigration on structural and cultural determinants of HIV-related stigma: implications for HIV care of Chinese immigrants

ABSTRACT Objectives: Asian Americans have poor HIV-related outcomes, yet culturally salient barriers to care remain unclear, limiting development of targeted interventions for this group. We applied the ‘what matters most’ theory of stigma to identify structural and cultural factors that shape the nature of stigma before and after immigration from China to the US. Design: Semi-structured interviews were conducted with 16 immigrants to New York from China, recruited from an HIV clinic and community centers. Deductive followed by focal inductive qualitative analyses examined how Chinese cultural values (lian, guanxi, renqing) and structural factors influenced stigma before and after immigration. Results: In China, HIV stigma was felt through the loss of lian (moral status) and limited guanxi (social network) opportunities. A social structure characterized by limited HIV knowledge, discriminatory treatment from healthcare systems, and human rights violations impinged on the ability of people living with HIV to fulfill culturally valued goals. Upon moving to the US, positions of structural vulnerability shifted to enable maintenance of lian and formation of new guanxi, thus ameliorating aspects of stigma. Conclusions: HIV prevention and stigma reduction interventions among Chinese immigrants may be most effective by both addressing structural constraints and facilitating achievement of cultural values through clinical, peer, and group interventions.

Housing Instability, Depression, and HIV Viral Load Among Young Black Gay, Bisexual, and Other Men Who Have Sex With Men in Atlanta, Georgia.

Housing instability is common among sexual minority youth. Research suggests that psychological distress, such as depression, may mediate the association between housing instability and poor HIV-related outcomes, but this hypothesis remains underexplored. Housing instability was assessed using two variables (residential moves in 6 months, and self-reported homelessness at any time since age 15 years). We examined cross-sectional relationships between the housing instability variables and detectable HIV-1 viral load (VL) in a sample of young Black gay, bisexual, and other men who have sex with men (YB-GBMSM) living with HIV (N = 81) in Atlanta, GA, in 2015-2016. Additionally, we explored whether depressive symptoms mediated this relationship. Our exploratory study suggests that psychological distress may partially mediate the association between housing instability and detectable VL. In addition to structural interventions that ensure housing stability, increasing use of mental health services by unstably housed YB-GBMSM may improve VL suppression in this high-risk population.

Patterns of alcohol use and associated characteristics and HIV-related outcomes among a sample of African-American women living with HIV

BackgroundAlcohol use is common among people living with HIV and negatively impacts care and outcomes. African-American women living with HIV are subject to vulnerabilities that may increase risk for alcohol use and associated HIV-related outcomes. MethodsWe used baseline data from a randomized controlled trial of an HIV-related stigma-reduction intervention among African-American women living with HIV in Chicago and Birmingham (2013–2015). Patterns of alcohol use [any use, unhealthy alcohol use (UAU), heavy episodic drinking (HED)] were measured using the AUDIT-C. We assessed demographic, social, and clinical characteristics which may influence alcohol use and HIV-related outcomes which may be influenced by patterns of alcohol use in bivariate and multivariable analyses. ResultsAmong 220 African-American women living with HIV, 54 % reported any alcohol use, 24 % reported UAU, and 27 % reported HED. In bivariate analysis, greater depressive symptoms, lower religiosity, lower social support, marijuana, and crack/cocaine use were associated with patterns of alcohol use (p < 0.05). Marijuana and cocaine/crack use were associated with patterns of alcohol use in adjusted analysis (p < 0.05). In adjusted analysis, any alcohol use and HED were associated with lower likelihood of ART adherence (ARR = 0.72, 95 % CI: 0.53-0.97 and ARR = 0.65, 95 % CI: 0.44-0.96, respectively), and UAU was associated with lack of viral suppression (ARR = 0.78, 95 % CI: 0.63-0.96). ConclusionsFindings suggest any and unhealthy alcohol use is common and associated with poor HIV-related outcomes in this population. Regular alcohol screening and intervention should be offered, potentially targeted to subgroups (e.g., those with other substance use).

Immigration Legal Services as a Structural HIV Intervention for Latinx Sexual and Gender Minorities.

Lack of legal immigration status is associated with poor HIV-related outcomes for immigrant Latinx sexual and gender minorities (LSGM). LSGM often meet eligibility criteria for legal immigration relief. A Medical-Legal Partnership (MLP) may thus be strategic to improve their health. We know little about the challenges LSGM face during the immigration legal process. We conducted in-depth interviews with six key informants and sixteen LSGM who recently applied for immigration legal relief. We coded and analyzed the data for emergent themes. Challenges to instituting an MLP for LSGM included lack of specialized training on working with SGM for immigration attorneys, and for clients: knowledge about legal deadlines, lack of housing and family support, and re-traumatizing experiences. Clients' outcomes were positive when attorneys and mental health providers collaborated. For LSGM, the benefits of immigration relief included reduced HIV risk. An MLP that addresses the surmountable challenges could improve HIV-related outcomes among LSGM.

Impact of intimate partner violence on clinic attendance, viral suppression and CD4 cell count of women living with HIV in an urban clinic setting

ABSTRACTThe substance abuse, violence and HIV/AIDS (SAVA) syndemic represents a complex set of social determinants of health that impacts the lives of women. Specifically, there is growing evidence that intimate partner violence (IPV) places women at risk for both HIV acquisition and poorer HIV-related outcomes. This study assessed prevalence of IPV in an HIV clinic setting, as well as the associations between IPV, symptoms of depression and PTSD on three HIV-related outcomes—CD4 count, viral load, and missed clinic visits. In total, 239 adult women attending an HIV-specialty clinic were included. Fifty-one percent (95% CI: 45%–58%) reported past year psychological, physical, or sexual intimate partner abuse. In unadjusted models, IPV was associated with having a CD4 count <200 (OR: 3.284, 95% CI: 1.251–8.619, p = 0.016) and having a detectable viral load (OR: 1.842, 95% CI: 1.006–3.371, p = 0.048). IPV was not associated with missing >33% of past year all type clinic visits (OR: 1.535, 95% CI: 0.920–2.560, p = 0.101) or HIV specialty clinic visits (OR: 1.251, 95% CI: 0.732–2.140). In multivariable regression, controlling for substance use, mental health symptoms and demographic covariates, IPV remained associated with CD4 count <200 (OR: 3.536, 95% CI: 1.114–11.224, p = 0.032), but not viral suppression. The association between IPV and lower CD4 counts, but not adherence markers such as viral suppression and missed visits, indicates a need to examine potential physiologic impacts of trauma that may alter the immune functioning of women living with HIV. Incorporating trauma-informed approaches into current HIV care settings is one opportunity that begins to address IPV in this patient population.

Association between internalized stigma and depression among HIV-positive persons entering into care in Southern India.

BackgroundIn India, which has the third largest HIV epidemic in the world, depression and HIV–related stigma may contribute to high rates of poor HIV–related outcomes such as loss to care and lack of virologic suppression.MethodsWe analyzed data from a large HIV treatment center in southern India to estimate the burden of depressive symptoms and internalized stigma among Indian people living with HIV (PLHIV) entering into HIV care and to test the hypothesis that probable depression was associated with internalized stigma. We fitted modified Poisson regression models, adjusted for sociodemographic variables, with probable depression (PHQ–9 score ≥10 or recent suicidal thoughts) as the outcome variable and the Internalized AIDS–Related Stigma Scale (IARSS) score as the explanatory variable.Findings521 persons (304 men and 217 women) entering into HIV care between January 2015 and May 2016 were included in the analyses. The prevalence of probable depression was 10% and the mean IARSS score was 2.4 (out of 6), with 82% of participants endorsing at least one item on the IARSS. There was a nearly two times higher risk of probable depression for every additional point on the IARSS score (Adjusted Risk Ratio: 1.83; 95% confidence interval, 1.56–2.14).ConclusionsDepression and internalized stigma are highly correlated among PLHIV entering into HIV care in southern India and may provide targets for policymakers seeking to improve HIV–related outcomes in India.

Attitudes of Indian HIV Clinicians Toward Depression in People Living with HIV

BackgroundDepression is highly prevalent in people living with HIV (PLHIV) and is associated with increased morbidity and mortality. In India, where access to mental health specialists is limited, little is known about the attitude of HIV clinicians toward depression in PLHIV. MethodsWe administered a questionnaire to HIV clinicians attending the 2015 Chennai Antiretroviral Therapy Symposium that assessed respondents' level of agreement with 29 statements regarding the etiology, importance, and management of depression and whether they felt capable and willing to manage depression in PLHIV. ResultsThe 69 respondents were from 9 Indian states. Most respondents agreed that depression in PLHIV is a serious problem (91%) and is associated with poorer HIV-related outcomes (62%-81%). Although most respondents (76%) reported feeling comfortable discussing mental health problems with PLHIV, almost half (48%) admitted that lack of knowledge and training about mental health issues hindered the diagnosis and treatment of depression in PLHIV. With few exceptions, there were no significant differences in responses by gender, urban/rural practice location, or government versus private practice. ConclusionsIndian HIV clinicians believe that depression in PLHIV is important and are willing to manage depression in the HIV primary care setting. These findings suggest that HIV clinicians require further training to deliver evidence-based interventions to treat PLHIV with depression.

State of HIV in the US Deep South.

The Southern United States has been disproportionately affected by HIV diagnoses and mortality. To inform efforts to effectively address HIV in the South, this manuscript synthesizes recent data on HIV epidemiology, care financing, and current research literature on factors that predispose this region to experience a greater impact of HIV. The manuscript focuses on a specific Southern region, the Deep South, which has been particularly affected by HIV. Epidemiologic data from the Centers from Disease Control and Prevention indicate that the Deep South had the highest HIV diagnosis rate and the highest number of individuals diagnosed with HIV (18,087) in 2014. The percentage of new HIV diagnoses that were female has decreased over time (2008-2014) while increasing among minority MSM. The Deep South also had the highest death rates with HIV as an underlying cause of any US region in 2014. Despite higher diagnosis and death rates, the Deep South received less federal government and private foundation funding per person living with HIV than the US overall. Factors that have been identified as contributors to the disproportionate effects of HIV in the Deep South include pervasive HIV-related stigma, poverty, higher levels of sexually transmitted infections, racial inequality and bias, and laws that further HIV-related stigma and fear. Interventions that address and abate the contributors to the spread of HIV disease and the poorer HIV-related outcomes in the Deep South are warranted. Funding inequalities by region must also be examined and addressed to reduce the regional disparities in HIV incidence and mortality.

Prevalence and correlates of psychosocial conditions among people living with HIV in southern India

ABSTRACTPsychosocial conditions such as depression, intimate partner violence (IPV), and history of childhood sexual abuse (CSA) have been associated with poor HIV-related outcomes. In India, which has the third largest HIV epidemic in the world, little is understood about the impact of psychosocial conditions on people living with HIV (PLHIV). We aimed to understand the prevalence and correlates of psychosocial conditions among PLHIV entering into HIV care at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India. Thirteen questions were added to the standard voluntary counseling and testing questionnaire, including the Patient Health Questionnaire-9 (a depression scale) and questions assessing for CSA and IPV. We fitted logistic regression models, stratified by gender, with psychosocial condition as the outcome of interest and substance use variables and socio-demographic variables as the correlates of interest. Three hundred and eighty-three persons were enrolled into the study; of these, 253 (66%) tested positive for HIV, including 149 men and 104 women, and were included in the models. More than one-quarter (28%) of the men and 19% of the women reported at least one psychosocial condition (probable depression, CSA, or IPV). In adjusted analysis, current alcohol use was associated with greater than two times higher odds of a psychosocial condition (Adjusted Odds Ratio = 2.24, 95% CI, 1.04–4.85) among men. In conclusion, we estimated the prevalence of probable depression, CSA, and IPV among PLHIV presenting for HIV care in southern India and found that, among male PLHIV, alcohol use was associated with a markedly higher odds of reporting a psychosocial condition. Further study is needed to characterize alcohol use among male PLHIV and the possible deleterious impact of psychosocial conditions and alcohol use on HIV-related outcomes in India.

Trauma history in African-American women living with HIV: effects on psychiatric symptom severity and religious coping

Women living with HIV (WLHIV) have rates of post-traumatic stress disorder (PTSD) up to 5 times higher than the general population. Individuals living with HIV and a concurrent diagnosis of PTSD have poorer HIV-related outcomes; however, the prevalence and impact of PTSD on African-American WLHIV seeking mental health treatment is unknown. The aim of this study is to examine the associations between PTSD symptoms with psychiatric symptom severity and psychological/religious coping strategies in African-American WLHIV who are seeking mental health treatment. This is a cross-sectional study of 235 African-American WLHIV attending an urban community mental health clinic. Bivariate analyses were conducted to evaluate associations between a PTSD symptoms scale (PSS ≥ 21 versus PSS < 21) and (1) psychiatric severity, (2) coping strategies, and (3) religious coping strategies. Thirty-six percent reported symptoms consistent with PTSD (PSS ≥ 21). These women were significantly more likely to have worse mental health symptoms and were more likely to employ negative psychological and religious coping strategies. On the contrary, women with a PSS < 21 reported relatively low levels of mental health symptoms and were more likely to rely on positive psychological and religious coping strategies. Over one-third of African-American WLHIV attending an outpatient mental health clinic had symptoms associated with PTSD. These symptoms were associated with worse mental health symptoms and utilization of dysfunctional religious and nonreligious coping strategies. Untreated PTSD in WLHIV predicts poorer HIV-related health outcomes and may negatively impact comorbid mental health outcomes. Screening for PTSD in WLHIV could identify a subset that would benefit from evidence-based PTSD-specific therapies in addition to mental health interventions already in place. PTSD-specific interventions for WLHIV with PTSD may improve outcomes, improve coping strategies, and allow for more effective treatment of comorbid mental health disorders.

Too Few HIV-Infected Patients Are Receiving Care

With potent antiretroviral therapy (ART) now available, attention is turning to failed retention in care as a cause of poor HIV-related outcomes. In