Disparities in Care Outcomes in Atlanta Between Black and White Men Who Have Sex With Men Living With HIV: Protocol for a Prospective Cohort Study (Engage[men]t)

Background The US HIV epidemic is driven by infections in men who have sex with men and characterized by profound disparities in HIV prevalence and outcomes for Black Americans. Black men who have sex with men living with HIV are reported to have worse care outcomes than other men who have sex with men, but the reasons for these health inequities are not clear. We planned a prospective observational cohort study to help understand the reasons for worse HIV care outcomes for Black versus White men who have sex with men in Atlanta. Objective The aim of this study is to identify individual, dyadic, network, neighborhood, and structural factors that explain disparities in HIV viral suppression between Black and White men who have sex with men living with HIV in Atlanta. Methods Black and White men who have sex with men living with HIV were enrolled in a prospective cohort study with in-person visits and viral suppression assessments at baseline, 12 months, and 24 months; additional surveys of care and risk behaviors at 3, 6, and 18 months; analysis of care received outside the study through public health reporting; and qualitative interviews for participants who experienced sentinel health events (eg, loss of viral suppression) during the study. The study is based on the Bronfenbrenner socioecological theoretical model. Results Men who have sex with men (n=400) were enrolled between June 2016 and June 2017 in Atlanta. Follow-up was completed in June 2019; final study retention was 80% at 24 months. Conclusions Health disparities for Black men who have sex with men are hypothesized to be driven by structural racism and barriers to care. Observational studies are important to document and quantify the specific factors within the socioecological framework that account for disparities in viral suppression. In the meantime, it is also critical to push for steps to improve access to care, including Medicaid expansion in Southern states, such as Georgia, which have not yet moved to expand Medicaid. International Registered Report Identifier (IRRID) DERR1-10.2196/21985

1 R01 AI112723-01A1 2 ZRG1 AARR-F (02) SULLIVAN, P 1R01AI112723-01A1 Sullivan, Patrick RESUME AND SUMMARY OF DISCUSSION: The applicant seeks to identify factors that explain the disparities in HIV infections among Black MSM compared to their White counterparts although the literature has not reported significant differences in the HIV risk behaviors of these populations. The applicant will leverage the infrastructure put in place for -InvolveMENt,-this team's previous study of MSM, and will continue to involve community stakeholders. In this application, however, the investigators will focus on a prospective cohort of HIV-positive MSM to identify factors that can explain the racial disparities in HIV prevention and care. This very experienced and productive applicant has gathered a team of outstanding collaborators; together, there is no doubt they can carry out this project successfully. This resubmission was generally very responsive to previous critiques; its focus on MSM, a population well documented to be at the highest risk of HIV in this country is important. The plan to elucidate racial disparities between Black and White MSM is significant in that it will inform more effective, targeted interventions for Black MSM who continue to sustain the highest rate of HIV infections among MSM. The application has many strengths; it focuses on the care continuum; uses a mixed methods design, and will collect biomarkers, and the retention plan is very strong. These raise confidence this project will contribute important new information to the field. Enthusiasm for this strong application would have been much higher still, were it not for concerns with some aspects of the methodology. The most critical of these include a lack of justification for conducting STI tests and for interviewing providers; a concern that only including MSM not planning to move for the next two years will bias the sample; a lack of clarity as to whether information will be gathered about these MSM's partners, especially given data showing the critical role of partners in the disparities in HIV infection between Black and White MSM. Other, concerns included sample sizes that are potentially too small, the application's grounding in two theoretical frameworks that may be mutually incompatible, the absence of hypotheses to frame the results, and an insufficient focus on the multi-level components of the related factors, as purported. Despite these, however, there is no doubt this application will contribute substantially to generating new knowledge in understanding racial disparities in HIV/AIDS.

DESCRIPTION (provided by applicant):
MSM are a key risk group in the United States and are disproportionately impacted in terms of HIV prevalence and incidence. For decades, black/white disparities in HIV prevalence and incidence have been recognized. Much of the dialogue about disparities has focused on what might cause disparities in new HIV infections, and we recently completed an NIMH-supported R01 (InvolveMENt) to examine reasons for black/white HIV disparities in an HIV/STI incidence cohort of black and white MSM in Atlanta. An early, important finding from that study is that HIV-negative black MSM, while having comparable levels of individual risk behaviors, have a much greater chance of having a sex partner with a detectable HIV viral loadthus black MSM are at higher risk for acquiring HIV, despite comparable individual risk behaviors. But disparities extend beyond risks for infection: black MSM may fare less well in the treatment cascade because of later access to care, lower adherence to antiretroviral therapy (ARV), mistrust of providers, or, perhaps, stigma and discrimination. Recent national estimates have documented consistent racial disparities at each step of the HIV treatment cascade, culminating in a 30% lower likelihood of viral suppression among black non-Hispanic, compared to white non-Hispanic HIV-positive individuals. This pattern has been observed in the state of Georgia. In a Lancet systematic review in 2012, Millet et al. illustrated that the racial disparities after HIV infection are profound for MSM: black MSM were found to be less likely to initiate ARVT, less likely to adhere to therapy, and less likely to be virally suppressed. Further, this analysis suggested that structural factors, such as education, poverty, and lack of employment, played key roles in care disparities. Thus, we propose to build on our previous MSM cohort in Atlanta, to identify the factors that are prospectively associated with racial disparities in effective HIV care and prevention. The proposed work will build on the infrastructure, community relationships, multilevel conceptual framework and multidisciplinary team assembled for our previous grant, but will shift focus from HIV-negative MSM to those living with HIV. The design will be a prospective cohort of HIV-positive black and white MSM in Atlanta, with rich laboratory, survey, and qualitative data collections. Results 1 R01 AI112723-01A1 3 ZRG1 AARR-F (02) SULLIVAN, P will help provide deeper understanding of why disparities in care outcomes occur, and will provide actionable data for the development of interventions to reduce disparities in effective HIV care.

PUBLIC HEALTH RELEVANCE:
Profound disparities in effective HIV care exist for black MSM compared to white MSM; the reasons are most likely related to structural and community factors. A cohort study of HIV-positive black and white MSM is proposed to further understanding of these disparities, and suggest possible interventions.

CRITIQUE 1:
Significance: 2 Investigator(s): 1 Innovation: 1 Approach: 2 Environment: 1 Overall Impact: This revised application proposes: Aim 1, to prospectively examine factors temporally associated with incident ineffective (and incident effective for Aim 2) medical care and prevention among MSM previously diagnosed (and newly diagnosed for aim 2) with HIV in Atlanta; Aim 3, to understand modifiable reasons for key missed opportunities for HIV care and prevention, by using nested, prospective qualitative data collections regarding -sentinel care events‖ or -sentinel prevention events. This is a highly meritorious, methodologically complex and ambitious study, with multiple sources of data that will generate a great deal of information. The study is highly descriptive, and although there is a theoretical explanatory model, there are no specific hypotheses. Thus, it is not completely clear what is the potential for explaining the ways in which health disparities relate to negative outcomes. Enthusiasm for impact is diminished by attempting to explain health disparities through comparisons between Black and White MSM rather than by specific mechanisms that exacerbate and perpetuate those disparities.

Significance: Strengths
Proposed aims are of significance. Findings will provide information to pursue causal models in future studies.

Weaknesses
Black-White comparison is not of significance; it is well documented that disparities between these two groups exist.
The applicants state that racial comparisons will help develop culturally appropriate interventions. Many culturally appropriate interventions have been developed without racial comparisons, but rather, by examining and understanding variability within racial groups.

Strengths
Very accomplished PI with great research experience. Capable of recruiting the samples and of carrying out ambitious data collection. He has an excellent record of delivering results.
Strong research team, mainly with biomedical expertise. Addition of Mr. Millet strengthens cultural competence of team.

Strengths
The use of nested, prospective, mixed methods qualitative data collections regarding sentinel care events and sentinel prevention events is highly innovative.
A prior reviewer questioned the innovation of examining cascade of care. The applicant has clarified that most studies have used cross-sectional data, whereas this study will use temporal, prospective data to examine the dynamics of the cascade of treatment from an ecological perspective.
Qualitative component, as described in this application, is innovative.

Weaknesses
None observed.

Strengths
Numerous strengths of this application; hard to list them all to do justice to application.
Excellent use of preliminary data to develop recruitment plan; it seems feasible to identify 80 undiagnosed infections, which is the most challenging group to identify. However, it may be more challenging to recruit an equal number of Black and White participants given lower incidence in the latter group.
Two-year follow-up with assessments will yield valuable information. Strong retention plan.
In-depth interviews to follow up sentinel cases are very well described and promise to be a model for other researchers.
Use of CASI, triangulation of in-depth interviews, biological data, medical chart abstraction.

Weaknesses
There are no specific hypotheses guiding quantitative analyses. It seems that the same conceptual model will be used for Black and White MSM. Given that the end point is viral suppression, as written, it seems findings will reiterate once again that there are racial disparities. The opportunity to understand how different factors intervene and interact to create disparate outcomes within Black MSM could be missed.
Conducting the analyses and interpreting results from so many sources of data can be unwieldy. Stepwise regression is not the most elegant way for analyzing the data. If there were more precise hypotheses, better analytic methods could be used.
Unclear why HIV screening will be done at 24 months; they are all living with HIV (Table 2). Similarly, no justification for STI testing is provided.
Minor: No questions about sexual behavior or adherence in measures section (Table 3), but presumably they are in survey as per text in application.
No justification for medical providers' interviews. As proposed, it might simply reflect the extent to which medical providers agree with Bonfenbrenner's model. Unclear if there is sufficient power in the sample of 80, half white, half black, to detect the race by time interaction. There is a risk that there will not be enough variability in the sample of 80.

Strengths
Emory University is an excellent environment to carry out the aims of the study.

Weaknesses
None observed.

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections No concerns; adequate protections.

Sex/Gender: Distribution justified scientifically
Race/Ethnicity: Distribution justified scientifically Inclusion/Exclusion of Children under 21: Including ages < 21 justified scientifically o Only men, all ages, justified scientifically.

Not Applicable (No Vertebrate Animals)
Biohazards:

Resubmission:
A concern brought up by previous reviewer may have not been completely addressed; nevertheless, the knowledge that this study will yield is invaluable. "Not clear why a need exists to verify previously documented prevalent racial disparities in previously diagnosed White and Black MSM".

Budget and Period of Support:
Recommend as Requested: The resources used to recruit a White sample could have been used to recruit a much larger Black sample, which would allow more robust statistical analyses, including SEM. This is 1 R01 AI112723-01A1 6 ZRG1 AARR-F (02) SULLIVAN, P particularly important for previously undiagnosed infections, because if all 80 were Black other more important questions could be addressed.
No budget for Mr. Millet, who says his contribution is inkind. How much effort will he be able to devote?

Additional Comments to Applicant (Optional):
o I recommend deleting interviews to health care providers as they are and use those resources to increase Black sample size.

CRITIQUE 2:
Significance: 2 Investigator(s): 1 Innovation: 4 Approach: 3 Environment: 1 Overall Impact: Previous studies that have been carried out to understand Black/White disparities in care, treatment, and prevention among Black MSM have largely been cross sectional. The current study, in Atlanta with HIV+ Black and White MSM, attempts to use a prospective analysis to examine factors that explain incident lack of success in the care continuum. The authors seek to use survey methods, chart extraction, biomarkers and qualitative data to identify multi-level factors that explain the lack of initiation and retention in medical care. They also seek to identify modifiable targets along the care continuum using an analysis of sentinel care events. The team has substantial success in this area of work previously, the environment is outstanding, and the applicants have adequately responded to most of the previous reviewer comments, and have made clear attempts to bolster the impact of the current application. While they have improved the application, there are a few missed opportunities: inclusion of partners, restrictive inclusion criteria concerning stating that one will not move in the next two years, and lack of analysis of masculinity in the model or the measures limits the impact somewhat. In addition, the application still is not clear on whether it is truly multi-level-many indicators appear to be on the individual level or are about perceptions of the neighborhood level despite previous findings in the researchers' own team that indicate the importance of partner and neighborhood effects. Finally, previous reviewers did note the importance of intervention development, and the team did not take this into account all that much aside from the identification of some perceptions of modifiable impact-that wasn't an entirely strong response, although it is responsive.

Strengths
There are not that many papers nor funded projects carried out on HIV+ Black MSM that seek to understand Black/White disparities in care and that identify the factors that explain lack of success along the care continuum All too many cross-sectional studies are carried out when focused on the care continuum-very few longitudinal Nuanced use of qualitative data to examine sentinel care and prevention events is likely to uncover modifiable domains

Weaknesses
Unclear work on providers is included in the qualitative analysis-HOW would providers be included in this study? How should they be? This was not a strong component of the proposal.
Lack of inclusion of partners and information about partners limits the usefulness given the importance of partners noted in the background information Level of analysis appears to be focused at multiple levels but measures are often at the individual level-the need for multi-level analysis is made very clear in this application but it is not fully brought to fruition

Strengths
This team has an outstanding background in this area of study, in this region, with excellent and long term success in recruiting and retaining study samples

Weaknesses
None noted

Strengths
While we do know that Black MSM fare poorly in the care continuum, we do not have enough information to intervene due to a lack of longitudinal data and a lack of nuanced understanding of the mechanisms through which health care disengagement occurs. This fills an important gap Temporal ecological lens is critical-far too many studies are focused at the individual level

Weaknesses
While the chart is very helpful on page 77 to show the lack of previous studies and funded research in this area of study, the authors did not make it entirely clear what we do know about the other studies focused on HIV+ MSM who are Black (aside from Millet's findings of structural factors being important and Sullivan & Rosenberg finding that couple level factors mattered). Thus, reviewers are not entirely able to evaluate the innovation. Nine studies are listed in the chart and 3 are discussed.

Strengths
Use of biomarkers, survey, medical record abstraction and qualitative work strengthen the application.
Reasonable changes have been made in the application that Indicate a real responsiveness to previous reviews, including removing restrictive inclusion criteria from the last round Weaknesses 1 R01 AI112723-01A1 8 ZRG1 AARR-F (02) SULLIVAN, P The lack of inclusion or information gathered on partners seems like an important omission given the importance of partners that was highlighted in the background information (e.g. less discussion of HIV status and partner less likely to be virally suppressed) There was no discussion of masculinity in the theoretical model, the literature review, the measures, or the analysis despite the fact that men frequently do not seek care due to ideals of strength, invulnerability, and more that are particularly relevant to Black MSM The requirement that MSM must not be planning on moving within the next 2 years limits the sample to those who are more economically well off and stable. This biases the sample in a direction that would yield far less helpful information focused on resolving problems found along the care continuum. After all, Black MSM are far more transient and economically disenfranchised Unclear if the authors have maximized the analytical utility of a multi-level model-not only whether they are examining whether 1 level affects another but also the model didn't seem to be truly capitalizing on/adequately measuring levels beyond individual?