A Web-Based Antiretroviral Therapy Adherence Intervention (Thrive With Me) in a Community-Recruited Sample of Sexual Minority Men Living With HIV: Results of a Randomized Controlled Study.

BACKGROUND: Most new HIV infections are attributed to male-to-male sexual contact in the United States. However, only two-thirds of sexual minority men living with HIV achieve an undetectable viral load (UVL). We tested a web-based antiretroviral therapy adherence intervention called Thrive with Me (TWM) with core features that included medication self-monitoring and feedback, HIV and antiretroviral therapy information, and a peer-to-peer exchange. OBJECTIVE: We assessed the efficacy of TWM on HIV UVL among adult (aged ≥18 years) sexual minority men. Moreover, we assessed the impact of overall engagement and engagement with specific intervention features on HIV UVL. METHODS: In total, 401 sexual minority men (mean age 39.1, SD 10.8 y; 230/384, 59.9% African American) in New York City were recruited between October 2016 and December 2019 and randomized to receive TWM (intervention) or a weekly email newsletter (control) for 5 months. Computerized assessments occurred at baseline and months 5, 11, and 17. The primary outcome was a dichotomous measure of HIV UVL (≤20 copies/µL). Generalized estimating equations with robust SEs were used to assess the effect of the TWM intervention on HIV UVL over the follow-up period in an unadjusted model and a model adjusted for baseline differences and then stratified by baseline recent drug use urinalysis. In secondary analyses, generalized linear models were used to estimate risk differences in the association of overall engagement with TWM (the sum of the number of days participants accessed ≥1 screen of the TWM intervention out of a possible 150 days) and engagement with specific TWM components on HIV UVL throughout the 17-month intervention period. RESULTS: Participant retention was 88.5% (355/401; month 5), 81.8% (328/401; month 11), and 80.3% (322/401; month 17). No consistent differences in HIV UVL were found between those randomized to receive TWM or the control at the 5- (difference-in-differences [DD]=-7.8, 95% CI -21.1 to 5.5), 11- (DD=-13.9, 95% CI -27.7 to 0.04), or 17-month (DD=-8.2, 95% CI -22.0 to 5.7) time points, or when stratified by baseline recent drug use. However, those TWM-assigned participants with high overall levels of engagement (in the upper 25th percentile) were more likely to have an HIV UVL at the end of the 5-month active intervention period compared to those with low engagement (below the 75th percentile; risk difference=17.8, 95% CI 2.5-33.0) or no engagement (risk difference=19.4, 95% CI 3.3-35.5) in the intervention. Moreover, high engagement with the peer-to-peer exchange was associated with HIV UVL over time in unadjusted models. CONCLUSIONS: TWM did not have overall impacts on HIV UVL; however, it may assist some sexual minority men who are highly engaged with this web-based intervention in achieving HIV viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov NCT02704208; https://clinicaltrials.gov/study/NCT02704208.

Examining inequities in rates of undiagnosed HIV and rectal STIs in a large nationwide cohort study of sexual minority men.

OBJECTIVE: Sexual minority men (SMM) of colour are disproportionately impacted by HIV and bacterial STIs (bSTIs). To better understand within-group heterogeneity and differential risk factors by race and ethnicity, we sought to examine rates of undiagnosed HIV and rectal bSTI at the intersection of racial and ethnic identity with other sociodemographic factors. METHODS: We examined data from 8105 SMM conducting home-based self-testing at enrolment in a nationwide cohort study collected from November 2017 to August 2018. We conducted analyses stratified by racial and ethnic groups to examine within-group (ie, subgroup) unadjusted rates of HIV and rectal bSTI infection across a range of characteristics. RESULTS: Rates of undiagnosed HIV were highest among Black (4.3%, n=39) and Latino (2.4%, n=38) SMM, with lower rates among those identified as multiracial (1.6%, n=15), white (1.3%, n=56) and other races (1.3%, n=6). Across the stratified analyses of HIV infection, 15 significant associations emerged showing that age, region, insurance type, sexual positioning and incarceration history had differential impacts across racial and ethnic groups. In particular, private and public insurance were protective against HIV for white but not Black and Latino SMM, and incarceration was associated with substantially higher rates of HIV infection for Black and Latino SMM relative to white SMM. We found significant co-occurrence of HIV and bSTI rates for participants who identified as Latino (OR=7.5, 95% CI 2.12 to 26.54), white (OR=3.19, 95% CI 1.14 to 8.98) and multiracial (OR=5.5, 95% CI 1.08 to 27.90), but not those who identified as Black (OR=0.82, 95% CI 0.10 to 6.56) or other races (OR=3.56 95% CI 0.31 to 40.80). CONCLUSIONS: Stratified analyses showed differential rates of HIV infection at the intersection of racial and ethnic groups with other characteristics, particularly insurance status and incarceration history, pointing to structural inequities rather than individual behaviours underlying disproportionately high rates of HIV for Black and Latino SMM.

An Examination of Gay Couples' Motivations to Use (or Forego) Pre-exposure Prophylaxis Expressed During Couples HIV Testing and Counseling (CHTC) Sessions.

While many gay couples perceive themselves to have little risk for HIV transmission, research estimates that 35-68% of new HIV infections are transmitted within main partnerships. Pre-exposure prophylaxis (PrEP) is recommended for those partnered gay and bisexual men (GBM) who engage in sex outside their primary relationship or who have an HIV-positive partner. There is reason to believe that couples' sero-status and sexual agreement will shape perceptions of PrEP's personal relevance among gay couples. The current study examined motivations for and ambivalence towards PrEP uptake reported in a sample of 67 gay couples during completion of a brief CDC-recommended prevention intervention: Couples HIV Testing and Counseling. Findings suggest that all types of couples identified some circumstances in which they would consider PrEP; however, PrEP messaging should be crafted to avoid undermining current prevention strategies or threatening the trust and legitimacy of the relationship.

Treatment Is More Than Prevention: Perceived Personal and Social Benefits of Undetectable = Untransmittable Messaging Among Sexual Minority Men Living with HIV.

Research suggests that the science of undetectable viral load (VL) status and HIV transmission-conveyed with the slogan "Undetectable = Untransmittable" or "U = U"-has gaps in acceptance despite robust scientific evidence. Nonetheless, growing acceptance of U = U creates conditions for a shift in the sociopolitical and personal implications of viral suppression. We conducted an online survey over a 23-month period in 2018 and 2019 among 30,361 adolescent and adult (aged 13-99) sexual minority men living with HIV (SMM-LHIV) across the United States. We examined the impact of U = U on self-image, potential for changing societal HIV stigma, whether SMM-LHIV had ever spoken with a provider about viral suppression and HIV transmission, and primary sources of hearing about U = U. Approximately 80% of SMM-LHIV reported that U = U was beneficial for their self-image and societal HIV stigma, 58.6% reported it made them feel "much better" about their own HIV status, and 40.6% reporting it had the potential to make HIV stigma "much better." The most consistent factors associated with these beliefs centered around care engagement, particularly self-reported viral suppression and excellent antiretroviral therapy adherence. Two-thirds reported ever talking to a provider about VL and HIV transmission, although the primary sources for having heard about U = U were HIV and lesbian, gay, bisexual, transgender, and queer (LGBTQ) news media and personal profiles on networking apps. These findings demonstrate the significant personal and social importance of U = U for SMM-LHIV that go above-and-beyond the well-documented health benefits of viral suppression, suggesting that providers should consider routinely initiating conversations with patients around the multifaceted benefits (personal health, sexual safety and intimacy, increased self-image, and reduced social stigma) of viral suppression.

Mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase kinase 1 protein expression is subject to translational regulation in prostate cancer cell lines.

Mitogen-activated protein kinase kinase 4/c-Jun NH(2)-terminal kinase kinase 1 (MKK4/JNKK1; hereafter referred to as MKK4) is a dual-specificity kinase with a critical role in regulating the activity of c-Jun NH(2)-terminal kinase and p38 kinases. We identified a novel biological function for MKK4 in the regulation of growth of ovarian and prostate cancer metastases. Clinical correlative studies showed that MKK4 protein levels were reduced in high-grade prostate cancer and prostate and ovarian cancer metastases compared with normal tissue, which prompted investigation into the mechanism(s) responsible for down-regulation of MKK4 in a panel of cancer cell lines. Initial studies found that low levels of MKK4 protein did not correlate with either exon deletion or decreased levels of MKK4 mRNA, suggesting that MKK4 protein levels were regulated posttranscriptionally by either reduced translation or reduced protein stability. Endogenous MKK4 was highly stable and not subject to altered proteolysis. Instead, MKK4 biosynthesis seemed to be regulated by altered translation. In support of this assertion, we found that cytosolic MKK4 mRNA was shifted toward active polysomes in cells with higher levels of MKK4 protein, suggesting that MKK4 mRNA was translated more efficiently in these cells. This study supports a novel mechanism for the regulation of MKK4 protein levels. Further, these findings have potential therapeutic implications for modulating the expression of a signaling kinase involved in the regulation of metastatic growth.