Stigma and discrimination related to HIV and AIDS ("HIV-related stigma") have been identified worldwide as major barriers to HIV treatment and care, posing challenges to HIV prevention efforts and provision of adequate care, support, and treatment. Despite decades of global efforts to tackle HIV-related stigma, previous interventions designed to reduce stigma have been largely ineffective. The knowledge gaps and challenges for combating HIV-related stigma are partly rooted in the complexity and diversity of the stigma and partly in the limitations in current conceptualization of stigma reduction efforts. Recent research, including our own preliminary data, has shown the promise of resilience approaches that focus on the development of strengths, competencies, resources, and capacities of people living with HIV (PLWH) and those of their real or surrogate family members and healthcare facilities to prevent, reduce, and mitigate the negative effects of stigma. However, the resilience approach, while hypothesized, has not been widely tested in intervention trials. In the current application, we propose to develop, implement, and evaluate a theory-guided, multilevel multimode resilience-based intervention via a stepped-wedge randomized trial among 800 PLWH and their real or surrogate family members as well as 320 healthcare providers in Guangxi, China where we have built a strong research infrastructure and community collaboration through NIH-funded research since 2004. The primary outcome will be viral suppression among PLWH, and the intermediate outcomes will include resilience resources at the levels of individuals, the real or surrogate family members, and healthcare facilities as well as chronic stress response and adherence to treatment and care. The proposed study is innovative as it addresses a number of knowledge gaps in HIV-related stigma reduction intervention research based on both a conceptualization of stigma reduction and advancement in intervention research methodology (e.g., multilevel and multi-component intervention modality, a stepped wedge design, the addition of biomarkers to assess the effects of stigma, and targeting primary HIV clinical outcomes such as viral suppression). The proposed research is significant as it addresses a critical public health issue in the US and globally. The proposed intervention protocol, if proven efficacious, has the potential to be replicated in other low- and middle-income countries to mitigate the negative impact of stigma on the HIV treatment and care continuum.

The finding from the HIV Prevention Trials Network (HPTN) 052 trial of a 96% reduction in HIV incidence among discordant couples when the HIV-positive partner receives antiretroviral therapy (ART) has led to the emergence of "treatment as prevention" as the dominant strategy to end the HIV epidemic in the US and worldwide. However, numerous obstacles continue to prevent appropriate treatment and optimal clinical outcomes, including stigma against people living with HIV (PLWH). This is a significant public health problem globally, particularly in low- and middle-income countries (LMICs), including China. Stigma and discrimination related to HIV and AIDS ("HIV-related stigma") interfere with seeking and receiving appropriate treatment and care, contribute to depression and other psychiatric disorders, lower individuals' quality of life, and produce worsening clinical outcomes among PLWH. Despite substantial global efforts to reduce HIV-related stigma, stigma and discrimination remain widespread and are among the most poorly understood aspects of the epidemic. Previous interventions designed to reduce stigma have been largely ineffective. These knowledge gaps and challenges for combating HIV-related stigma are partly rooted in the complexity of the stigma experience, and partly in the limitations in the current conceptualization of stigma reduction efforts.

Recent research, including our own preliminary data, has suggested the potential utility of adopting a resilience-based approach that focuses on the development of strengths, competencies, resources, and capacities in PLWH, as well as their families and health care systems to reduce and actively mitigate the negative effects of stigma. However, this approach, while hypothesized, has not been empirically tested in longitudinal studies or intervention trials. In the current application, we propose to develop, implement, and evaluate a theory-guided, multilevel, multimodal resilience-based intervention via a stepped wedge cluster randomized trial among 800 PLWH and their real or surrogate family members as well as 320 health care providers in Guangxi, China where we have built a strong research infrastructure and community collaboration through NIH-funded research since 2004. The primary outcome will be viral suppression and the intermediate outcomes will include resilience resources at the level of the individual, the family, and the health care system, as well as psychological stress and medical adherence. In addition to self-reported data (e.g., depression and anxiety, adherence to treatment and care), biomarkers of stress (hair cortisol) and ART adherence (hair antiretroviral [ARV] concentration) will be employed. The proposed study has the following specific aims and research hypotheses:

Specific Aim#1: Develop a multilevel resilience-based intervention engaging PLWH, their real or surrogate family members (i.e., either "family of origin" or "family of choice"), and health care providers (HCPs); the intervention will target individual factors (e.g., resilience, self-efficacy), family factors (e.g., supportive family members), and structural factors (e.g., supportive HCPs and care facilities) by adapting existing intervention components that have shown preliminary efficacy in China or elsewhere; Specific Aim#2: Test the short-, medium-, and long-term efficacy of the intervention through a cluster randomized stepped wedge trial among 800 PLWH-family member dyads and 320 HCPs from 40 HIV clinics in Guangxi with a longitudinal follow-up over a period of 36 months in 6-month intervals; Specific Aim #3: Identify individual and contextual factors that may mediate or moderate the effect of the intervention on viral suppression, other clinical outcomes (e.g., CD4 Lymphocyte count, quality of life), and the intermediate psychosocial and behavioral outcomes (e.g., resilience, stress, medical adherence); Hypothesis #1: Compared to the control condition (either within clusters or cross clusters in the stepped wedge trial), PLWH in the intervention condition will demonstrate: a) increases in personal resilience strengths and perceived support from family members and HCPs; b) decreases in psychological stress; c) increases in medication adherence, as measured by both self-report and biomarkers; and d) improved viral suppression and other clinical, virologic, and immunologic endpoints; Hypothesis #2: Compared to the control condition, the proposed family and HCP interventions will decrease stigmatizing attitudes/practices toward PLWH at both individual (e.g., family members, HCPs) and institutional (e.g., health care facilities) levels and will increase participants' willingness and level of comfort to support and assist PLWH in engaging in appropriate treatment and care; Hypothesis #3: A number of individual and contextual factors will mediate or moderate the effects of the proposed intervention on intermediate outcomes and endpoint clinical outcomes; such factors may include socio-economic status, intersecting stigma, perceived social support from other community members, disclosure experiences, and other barriers to medication adherence.

PLWH.

The eligibility criteria for PLWH include:

1) at least 18 years of age; 2) a confirmed diagnosis of HIV or AIDS; 3) with a detectable viral load (i.e., viral load≥50 copies/mL) or a viral round during the past year (a confirmed detectable viral load following a suppression); 4) willing to refer or give permission for us to contact one of their adult family member (either of origin or of choice) to participate (but the decision to participate will solely reside in the family member); 5) willing to provide a hair sample for test of hair cortisol and ARV hair concentration; 6) willing to consent the retrieval of their past and recent CD4 count and viral load from their medical charts; and 7) willing to be randomized to intervention condition at different time point in the stepped wedge trial.

The exclusion criteria for PLWH include

1. mental or physical inability to respond to assessment questions or to participate in intervention;
2. currently incarcerated or institutionalized for drug use or commercial sex;
3. participating in other intervention activities during the current study period; and
4. plan to permanently relocate outside of the province within a year. Physical and developmental inability will be screened by the local research team in consultation with physicians at the participating clinics.

Family members. The eligibility criteria for family members include

1. at least 18 years of age;
2. either family member of origin or family member of choice who provide emotional and other social support to study PLWH;
3. have been referred by case PLWH to participate in the study; and
4. willing to be randomized (along with study PLWH) to intervention condition.

The exclusion criteria for family members will be the same as PLWH.

Note: An HIV-infected family member will be eligible to participate. The decision of the family member to or not to participate will not affect the eligibility of PLWH to participate. Based on our experience working with PLWH in Guangxi, we anticipate that at least 80% of the referred family members will participate. With appropriate consent, we will collect brief information (e.g., key demographic characteristics and treatment profiles) on those PLWH who either cannot identify a family member (of origin or of choice) or her/his family member refuses to participate for potential secondary analysis to inform the refinement and scale-up of the proposed intervention in the future.

Health care providers. The eligibility criteria for health care providers include:

1. at least 18 years of age;
2. provides health care services at one of the participating HIV clinics; and
3. has regular contact with HIV-infected patients. The exclusion criteria for health care providers include

1) a plan to permanently relocate outside of the province within a year.