Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: Building Mobile HIV Prevention and Mental Health Support in Low-resource Settings

Summary: This project is designed to remedy unaddressed and interlocking HIV-prevention and mental health needs among gay and bisexual men (GBM) in the Central Eastern European country of Romania, and their underpinning stigma-related mechanisms. Rampant stigma contributes to the increasing prevalence of HIV among Romanian GBM (from under 10% in 2009 to close to 20% in 2014, by best available estimates) and keeps GBM out-of-reach of HIV-prevention services. An mHealth pilot intervention (titled "Despre Mine. Despre Noi." [DMDN] translated as "About Me. About Us."), which reduced Romanian GBM's risk for HIV infection while also reducing depression and alcohol abuse in an initial pre-post trial, is now ready for testing in a randomized controlled trial with a large national sample in the current study, entitled Comunică (translation: Communicate). The Comunică intervention entails eight 60-minute live chat sessions delivered by trained counselors on a mobile study platform using motivational interviewing (MI) and cognitive-behavioral skills training (CBST). First, during pre-trial (mos 1-5), in collaboration with a community advisory board consisting of GBM community members, GBM-affirmative physical and mental health providers, and a technical developer, the investigators will fine-tune the Comunică intervention based on the investigators' pilot findings and evaluation interviews, and expand the original DMDN education materials for an education attention condition (EAC) that will serve as control. Second, during the intervention phase (mos 6-45), the investigators will recruit, screen, assess, and randomize GBM at risk for HIV infection and alcohol abuse to either the Comunică intervention (n=163) or EAC (n=163). The conditions are content matched, and both are hosted on the study platform. While Comunică will consist of eight weekly mHealth live chat sessions, EAC will consist of eight self-administered educational modules. Third, during the follow-up phase (mos 8-55), the investigators will assess at 4, 8, and 12 months post-baseline, in a mobile fashion identical to the baseline, the primary outcome of condomless anal sex with male partners and secondary outcomes of alcohol abuse, depression, biologic HIV/STI infection, HIV/STI testing, and psychosocial mechanisms rooted in the Information-Motivation-Behavioral Skills (IMB) model (e.g., HIV/STI knowledge, condom use self-efficacy) and minority stress theory (e.g., identity concealment, internalized homophobia).

Detailed description: Recruitment. Cities. 326 GBM living in or 40-miles within 10 cities (i.e., București, Brașov, Timișoara, Cluj-Napoca, Iași, Constanța, Suceava, Craiova, Galați, Satu Mare) will be recruited and screened for the trial. In selecting these cities, the investigators sought to cover all regions of the country and capture areas of increasing HIV risk.
  Numbers. The investigators set the study total sample at 326 based on power calculations (136 participants will finish per arm accounting for a conservative 20% attrition).
  Venues. The investigators will post study ads on local collaborators' websites, subscriber lists, and key virtual venues (e.g., Grindr, Facebook), as in the pilot successful pilot, where 45% of participants were recruited on Grindr and 41% on Facebook. The investigators will also recruit using word-of-mouth. Trained recruitment staff will approach men in GBM-prevalent venues (bars; known public cruising areas, such as central train stations) across 10 cities. Recruitment staff will conduct quarterly recruitment trips to 9 cities (as they reside in Bucharest) following a rotating schedule. Furthermore, pilot participants who agreed to be contacted for the very purpose of recruiting within their GBM networks will advertise the study within these networks. Finally, enrolled participants will be encouraged to spread the word.
  Screening. Potential participants will complete an eligibility screener on Qualtrics.com, a research-designated secure online software. Eligible GBM will have the option to provide contact information at the end of the screener, in a separate survey, in order for research staff to later contact them for consent.
  Consent. Eligible participants will be contacted within days of screening for consent by affiliated project staff with whom the investigators collaborated on the pilot. Participants will be assigned a numeric identification and undergo the phone consent process used in the pilot. Research staff and participants will read through the entire electronic consent document (10 min). Points of confusion will be clarified and those still interested in participating will submit an electronic consent.
  Baseline assessment. After consent, participants will be sent their unique study ID and an electronic link to their Qualtrics-based baseline (BL) assessment (45 min).
  Randomization. After BL, participants will be block randomized to the Comunică (n=163) or EAC (n=163) condition. Qualtrics will stratify participants into randomly chosen blocks of 4 and 6 according to: baseline # CAS acts and # past-3-mo alcohol abuse days. After HIV/STI testing (below), Comunică participants will be randomly assigned to counselors so that all counselors always have an equal case load. Counselors will contact their assigned participants via preferred contact method to schedule the first session, when they will both log onto the mHealth platform. Comunică sessions and EAC modules span 3 months. Participants can use any mobile device (smartphone, tablet, laptop).
  Comunică Intervention. The intervention aims to support GBM in reducing their CAS and alcohol abuse and improving their mental health. Comunică is delivered over eight 60-min live chat sessions on an mHealth study platform compatible with any mobile device (laptops, smartphones). Comunică is based on the Information-Motivation-Behavioral Skills (IMB) model of health behavior change, which postulates that individuals must possess the requisite information for enacting sexual health, motivation to change their HIV risk and alcohol use, and behavioral skills necessary for reducing their risk. Therefore, Comunică includes MI to provide accurate information about HIV transmission, alcohol abuse, and local GBM-affirmative health resources (e.g., HIV-testing sites) and build motivation to improve behavioral skills (via CBST). MI is an evidence-based form of person-centered therapeutic communication that privileges client values and preferences for change to help individuals resolve ambivalence and move toward their valued goals. Skills-building is often a natural outcome of MI, especially for individuals who attain a high degree of motivation for change. CBST is a therapeutic approach used in the treatment of various behavioral problems, such as alcohol abuse and depression and more recently HIV risk. CBST can help modify cognitions driving unhealthy behaviors, promote awareness of contextual triggers and unhealthy behavioral patterns, and teach coping skills to improve health. Comunică also draws upon minority stress theory recognizing that stigmatizing societal contexts compromise health behavior. GBM in highly stigmatizing contexts such as Romania experience a lack of structural protections (e.g., national policies), institutional support (e.g., GBM-affirmative healthcare), and coping resources (e.g., social support). Thus, the CBST skills in Comunică are presented in a manner that acknowledges the barriers that social stigma poses to GBM's health, while empowering them to circumvent these barriers by building self-efficacy, effective communication, and planful problem-solving. All participants will receive referrals to GBM-affirmative psychologists trained by the investigators. DMDN Safety. Protocols include instructions for protecting participants' identities, data, and safety. Comunică is unable to address pre-exposure prophylaxis (PrEP). PrEP is not available in Romania and it would be unhelpful and likely unethical to discuss this inaccessible prevention tool. However, the investigators' long-term agenda includes working with NGOs to promote PrEP in Romania.
  The EAC Condition. The EAC condition consists of eight modularized topics (Appendix 1), content-matched with the Comunică sessions, which the investigators have generated based on HIV-prevention education with GBM in the US and Romania. Topics include 1) GBM identity, 2) "HIV 101," 3) HIV/STI testing, 4) alcohol and the body, 5) the role of alcohol in HIV risk, 6) HIV-status disclosure and sexual health communication, 7) IPV and finding social supports, and 8) summary. The content is preliminary and will be refined with the CAB. To maintain uniformity of information exposure across participants and maximize learning, each screen will be timed at a comfortable speed and participants will be unable to advance to the next screen prior to the set time limit. EAC participants will receive five quiz questions after each module, with correct answers in a following screen.
  Retention. The investigators will utilize retention strategies that yielded a 93% retention rate from BL to 26-month follow-up in the pilot. The investigators will: 1) build strong rapport, 2) update contact information often, 3) use all means of communication permitted by participants, and 4) send frequent reminders.
  HIV/STI Testing, Counseling, and Linkage to Services. All study participants will be tested for HIV, gonorrhea, and chlamydia at BL and 12-month follow-up, and, if positive, will be linked to care. The investigators have developed the HIV/STI protocol with ARAS (translated as the Romanian Association against AIDS), which contributes a 25-year experience in HIV/STI testing and care and demonstrates unusually high GBM-sensitive testing expertise for Romania. The investigators will convene with ARAS testing counselors to review protocols and set up all communication systems (i.e., with participants, IDPs) and results reporting. Procedures. After consent, the Project Coordinator will provide ARAS with the participant's information. An assigned ARAS testing counselor will contact the participant to provide two options: 1) mail an HIV/STI test kit to their home or 2) have the participant pick up the test at the study's infectious disease physician's (IDP) office in the region where the participant lives. The investigators provide these options based on the feedback they received from Romanian GBM, some of whom prefer not to receive such a package at home due to privacy concerns. Testing. Participants will receive a self-testing kit containing an HIV and syphilis test by drawing one drop of blood from their finger, and swabs and urine collection container for pharyngeal, rectal and urethral testing of chlamydia and gonorrhea (Cobas® Taqman® CT/NG PCR, Roche Molecular Diagnostics) to be performed by SH24, a UK-based partner for HIV/STI testing service. The kits will contain instructions in Romanian, and the ARAS testing counselors will conduct phone-based VCT and walk participants through testing steps. After self-testing, participants will mail the specimens in a prepaid discrete envelope to ARAS, who will then mail those to SH24 for analysis. SH24 will report results to ARAS within 3-5 days, at which time ARAS counselors will call participants to discuss results. Confidentiality of results will be stressed during consent and contact with ARAS staff, and on the kit instructions. Counseling. The investigators base their testing protocols on the CDC's voluntary counseling and testing (VCT) guidelines and WHO guidelines for self-testing. VCT will consist of one 45-min phone session. By phone, ARAS HIV-test counselors will conduct pre-test counseling for all participants and post-testing counseling for positive or inconclusive results, with linkage to care to local study-affiliated IDPs. Home testing has proven to be highly acceptable globally Only participants who receive an HIV-negative test result are eligible to participate in the study. Test result reporting. SH24 will report STI results to participants and ARAS. Negative results. Participants will be encouraged by the ARAS counselor to re-test every three months with the IDP in their area. IDP information will be provided on the online study platforms of all participants. Positive or inconclusive results. Instructions about steps to follow for reactive tests will be included in the testing kit and will be repeated by the ARAS counselor on the phone. The participant will receive the name and contact information of the study-affiliated IDP in their area.
  Baseline (BL), 4-, 8-, and 12-month assessments. The project coordinator will send a link to the BL survey to all HIV-negative participants, and tell them that they will be contacted by their counselor after submitting the survey. The quarterly self-administered mobile assessments are identical, take 45 min. to complete, have been validated by the Romanian pilot gay and bisexual men participants, and assess: 1) sexual behavior (e.g., # condomless anal sex acts; number and types of partners; sex under the influence) and 2) past-3-mo alcohol use; 3) depressive symptoms; 4) HIV/STI testing and other healthcare access (e.g., annual exams; mental health) patterns; 5) hypothesized mediators of intervention efficacy, including IMB model components (e.g., HIV-risk-related information, motivation, behavioral skills) and minority stress or (e.g., outness, internalized homonegativity, collective self-worth); 6) demographics and psychosocial risk contexts. During the follow-up phase (mos 8-55), the investigators will assess at 4, 8, and 12-mos post-baseline, in the same mobile fashion as the baseline, the primary outcome of condomless anal sex (CAS) with male partners, and secondary outcomes of alcohol abuse, depression, biologic HIV/STI infection, HIV/STI testing, and psychosocial mechanisms rooted in the Information-Motivation-Behavioral Skills (IMB) model (e.g., HIV/STI knowledge, condom use self-efficacy) and minority stress theory (e.g., identity concealment, stigma consciousness).

Eligibility: Inclusion Criteria:
  -  Gay and bisexual men will be eligible if they report: 1) male sex at birth and current male identity; 2) ≥ age 16; 3) ≥ 3 acts of condomless anal sex with an HIV-positive or status-unknown male partner in the prior 3 months; 4) ≥ 15 heavy drinking days in the prior 3 months, (e.g., binge drinking as defined by SAMHSA: ≥ 5 standard alcoholic drinks on five occasions per month); 5) own a mobile device (smartphone, tablet, laptop); and 6) are confirmed to be HIV-negative upon testing at study baseline.
  Exclusion Criteria:
  -  As severe mental illness poses barriers to participation, GMB will be excluded if they report past-year: (a) psychiatric hospitalization, (b) psychotic and manic symptoms, or (c) current mood-stabilizing or anti-psychotic medication prescription. Lastly, we will exclude participants based on any condition that, in the principal investigators' judgment, interferes with safe study participation.

Relevance to patient case: not relevant