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In this fifth decade of the human immunodeficiency virus (HIV) epidemic, central nervous system (CNS) complications including cognitive impairment and mental health remain a burden for people with HIV (PWH) on antiretroviral therapy. Despite the persistence of these complications, which often co-occur, the underlying pathophysiology remains elusive and consequently treatments remain limited. To continue to grow our understanding of the underlying mechanisms of CNS complications among PWH, there is a need to reexamine our current approaches, which are now more than 2 decades old. At the 2021 National Institutes of Health-sponsored meeting on Biotypes of CNS Complications in PWH, the Neurobehavioral Working Group addressed the following: (1) challenges inherent to determining CNS complications; (2) heterogeneity in CNS complications; and (3) problems and solutions for examining integrated biotypes. The review below provides a summary of the main points presented and discussed by the Neurobehavioral Working Group at the meeting.

Food insufficiency is associated with suboptimal HIV treatment outcomes. Less is known about psychosocial correlates of food insufficiency among PLWH. This sample includes 1176 adults initiating antiretroviral therapy at HIV clinics in Ethiopia. Logistic regression modeled the association of psychological distress, social support, and HIV-related stigma with food insufficiency. Among respondents, 21.4% reported frequent food insufficiency. Psychological distress [adjusted odds ratio (aOR) 2.61 (95% CI 1.79, 3.82)], low social support [aOR 2.20 (95% CI 1.57, 3.09)] and enacted stigma [aOR 1.69 (95% CI 1.26, 2.25)] were independently associated with food insufficiency. Food insufficiency interventions should address its accompanying psychosocial context.

The federal Ending the HIV Epidemic (EHE) initiative was created to reduce new US HIV infections, largely through pre-exposure prophylaxis and HIV treatments that reduce HIV transmissibility to zero. Behavioral health disorders (mental health and substance use) remain significant barriers to achieving EHE goals. Addressing behavioral health (BH) disorders within HIV primary care settings has been promoted as a critical EHE strategy. Implementation of efficacious HIV-BH care integration and its impact on HIV-related health outcomes is not well documented. In a federally-funded, exploratory phase implementation science study, we used the Collective Impact Framework to engage partners in seven EHE jurisdictions about the feasibility, acceptability, and sustainability of implementing HIV-BH integration interventions within local HIV settings. Partners concluded that full integration will remain the exception unless health systems invest in collaborative practice, professional training, appropriate health technology, and inter-system communication. Partners supported smaller incremental improvements including transdiagnostic approaches to reinforce each team member's sense of value in the shared endeavor. This early phase implementation science study identified research and implementation gaps that are critical to fill to end the HIV epidemic. Both the Collective Impact Framework and implementation science show promise for guiding future implementation of evidence-based HIV-BH intervention integration. [ABSTRACT FROM AUTHOR]

Introduction: There is an urgent need to identify men who have sex with men (MSM) living with HIV with unsuppressed viral loads to prevent transmission. Though respondent-driven sampling (RDS) is traditionally used for hard-to-reach populations, we compare how RDS and direct recruitment (DR) perform in identifying MSM living with HIV with unsuppressed viralloads and identifying MSM with socio-demographics characteristic of hard-to-reach populations. Methods: This is a cross-sectionalanalysis among 1305 MSM who were recruited from March 2016 to December 2017 for a case management intervention trial(HPTN 078). We recruited participants across four cities using RDS and DR methods: Birmingham, AL; Atlanta, GA; Baltimore, MD; and Boston, MA. Participants completed a socio-demographic questionnaire and underwent HIV testing. We compare the proportion of MSM with HIV and unsuppressed viralloads (HIV RNA [greater than or equal to] 1000 copies/ml) based on recruitment method using Pearson chi-square tests. We also compare differences in race, income, healthcare coverage, education, sexual orientation, hidden sexuality and comfort with participating in the LGBT community between recruitment methods and perform non-parametric trend tests to see how demographics change across RDS recruitment waves. Results: RDS recruited 721 men (55.2%) and DR yielded 584 men (44.8%). Overall, 69% were living with HIV, of whom 18% were not virally suppressed. HIV prevalence was higher among those recruited via DR (84%) compared to RDS (58%), p < 0.0001. Twenty per cent of DR recruits were not virally suppressed compared to 15% of RDS, though this was not significant. DR yielded a significantly higher proportion of Black participants and those with less than a high school diploma. The prevalence of low income, no healthcare coverage, bisexuality and hidden sexuality increased across RDS waves. Conclusions: DR was more efficient in identifying MSM living with HIV with unsuppressed viral loads; however, there was a higher proportion of hard-to-reach MSM who were low income, lacked health coverage, were bisexual and were not open with their sexuality in deeper waves of RDS. Researchers should consider supplementing RDS recruitment with DR efforts if aiming to identify MSM with unsuppressed viral loads via RDS. Keywords: ARV; co-infection; HIV epidemiology; men who have sex with men; recruitment; viral suppression, 1 | INTRODUCTION The HIV epidemic in the United States has disproportionately affectedgay,bisexual and other men who have sex with men (MSM) since the first cases were identified in the [...]

ObjectiveRegular HIV RNA testing for all HIV-positive patients on antiretroviral therapy (ART) is expensive and has low yield since most tests are undetectable. Selective testing of those at higher risk of failure may improve efficiency. We investigated whether a novel analysis of adherence data could correctly classify virological failure and potentially inform a selective testing strategy.DesignMultisite prospective cohort consortium.MethodsWe evaluated longitudinal data on 1478 adult patients treated with ART and monitored using the Medication Event Monitoring System (MEMS) in 16 US cohorts contributing to the MACH14 consortium. Because the relationship between adherence and virological failure is complex and heterogeneous, we applied a machine-learning algorithm (Super Learner) to build a model for classifying failure and evaluated its performance using cross-validation.ResultsApplication of the Super Learner algorithm to MEMS data, combined with data on CD4 T-cell counts and ART regimen, significantly improved classification of virological failure over a single MEMS adherence measure. Area under the receiver operating characteristic curve, evaluated on data not used in model fitting, was 0.78 (95% confidence interval: 0.75 to 0.80) and 0.79 (95% confidence interval: 0.76 to 0.81) for failure defined as single HIV RNA level >1000 copies per milliliter or >400 copies per milliliter, respectively. Our results suggest that 25%-31% of viral load tests could be avoided while maintaining sensitivity for failure detection at or above 95%, for a cost savings of $16-$29 per person-month.ConclusionsOur findings provide initial proof of concept for the potential use of electronic medication adherence data to reduce costs through behavior-driven HIV RNA testing.

BackgroundSouth Africa adopted a universal test and treatment program for HIV infection in 2015. The standard of care that people living with HIV receive consists of 3 sessions of readiness counseling delivered by lay counselors (LCs). In the largest antiretroviral therapy (ART) program worldwide, effective and early HIV and ART education and support are key for ensuring ART adoption, adherence, and retention in care. Having LCs to deliver readiness counseling allows for the wide task-sharing of this critical activity but carries the risks of loss of standardization, incomplete content delivery, and inadequate monitoring and supervision. Systems for ensuring that a minimum standard of readiness counseling is delivered to the growing number of people living with HIV are essential in the care cascade. In resource-constrained, high-burden settings, mobile health (mHealth) apps may potentially offer solutions to these treatment gaps by providing content structure and delivery records. ObjectiveThis study aims to explore, at a large Cape Town–based nonprofit HIV care organization, the staff’s perceived preimplementation barriers and facilitators of an mHealth intervention (Masivukeni) developed as a structured app for ART readiness counseling. MethodsMasivukeni is a laptop-based app that incorporates written content, graphics, short video materials, and participant activities. In total, 20 participants were included in this study. To explore how an mHealth intervention might be adopted across different staff levels within the organization, we conducted 7 semistructured interviews (participants: 7/20, 35%) and 3 focus groups (participants in 2 focus groups: 4/20, 20%; participants in 1 focus group: 3/20, 15%) among LCs, supervisors, and their managers. In total, 20 participants were included in this study. Interviews lasted approximately 60 minutes, and focus groups ranged from 90 to 120 minutes. The Consolidated Framework for Implementation Research was used to explore the perceived implementation barriers and facilitators of the Masivukeni mHealth intervention. ResultsSeveral potential facilitators of Masivukeni were identified. Multimedia and visual elements were generally regarded as aids in content delivery. The interactive learning components were notably helpful, whereas facilitated updates to the adherence curriculum were important to facilitators and managers. The potential to capture administrative information regarding LC delivery and client logging was regarded as an attractive feature. Barriers to implementation included security risks and equipment costs, the high volume of clients to be counseled, and variable computer literacy among LCs. There was uncertainty about the app’s appeal to older clients. ConclusionsmHealth apps, such as Masivukeni, were perceived as being well placed to address some of the needs of those who deliver ART adherence counseling in South Africa. However, the successful implementation of mHealth apps appeared to be dependent on overcoming certain barriers in this setting.

Introduction: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets. Methods: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets--90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed--or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020. Results: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively. Conclusions: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM. Keywords: HIV infections; incidence; homosexuality, male; models, theoretical; United States; forecasting, 1 | INTRODUCTION HIV incidence and prevalence remain high among gay, bisexual and other men who have sex with men (MSM) in the United States (US) [1-3]. Baltimore, Maryland (population [...]

Abstract Background Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown. Findings In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence. Conclusions The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study.

Acute/early HIV infection is a period of high risk for HIV transmission. Better understanding of behavioral aspects during this period could improve interventions to limit further transmission. Thirty-four participants with acute/early HIV infection from six US cities were assessed with the Mini International Diagnostic Interview, Beck Depression Inventory II, State-Trait Anxiety Inventory, Brief COPE, and an in-depth interview. Most had a pre-HIV history of alcohol or substance use disorder (85%); a majority (53%) had a history of major depressive or bipolar disorder. However, post-diagnosis coping was predominantly adaptive, with only mild to moderate elevations of anxious or depressive mood. Respondents described challenges managing HIV in tandem with pre-existing substance abuse problems, depression, and anxiety. Integration into medical and community services was associated with adaptive coping. The psychiatric context of acute/early HIV infection may be a precursor to infection, but not necessarily a barrier to intervention to reduce forward transmission of HIV among persons newly infected.

Risk reductions behaviors are especially important during acute/early HIV infection, a period of high transmission risk. We examined how sexual behaviors changed following diagnosis of acute/early HIV infection. Twenty-eight individuals completed structured surveys and in-depth interviews shortly after learning of their infection and 2 months later. Quantitative analyses revealed significant changes after diagnosis, including reductions in total partners and decreases in the proportion of unprotected sex acts occurring with uninfected partners (serosorting). Qualitative findings indicated that these changes were motivated by concerns about infecting others. However, participants were less successful at increasing the frequency with which they used condoms. These results suggest that the initial diagnosis with HIV may constitute an important component of interventions to promote risk reduction during the acute/early stages of the disease.

Acute/early HIV infection plays a critical role in onward HIV transmission. Detection of HIV infections during this period provides an important early opportunity to offer interventions which may prevent further transmission. In six US cities, persons with acute/early HIV infection were identified using either HIV RNA testing of pooled sera from persons screened HIV antibody negative or through clinical referral of persons with acute or early infections. Fifty-one cases were identified and 34 (68%) were enrolled into the study; 28 (82%) were acute infections and 6 (18%) were early infections. Of those enrolled, 13 (38%) were identified through HIV pooled testing of 7,633 HIV antibody negative sera and 21 (62%) through referral. Both strategies identified cases that would have been missed under current HIV testing and counseling protocols. Efforts to identify newly infected persons should target specific populations and geographic areas based on knowledge of the local epidemiology of incident infections.

BackgroundNeurocognitive impairment (NCI) is one of the most common complications of HIV infection, and has serious medical and functional consequences. South Africa has 7 million people living with HIV (PLHIV) with up to three-quarters of antiretroviral therapy (ART)-naïve individuals having NCI. South Africa’s health system struggles to meet the care needs of its millions of PLHIV; screening for NCI is typically neglected due to limited clinical staff trained to administer, score, and interpret neuropsychological tests, as well as long test batteries and limited screening tools for South African populations. Without accurate, clinically useful, and relatively brief NCI screening tests that can be administered by all levels of clinical staff, critical opportunities to provide psychoeducation, behavioral planning, additional ART adherence support, and adjuvant therapies for NCI (when they become available) are missed. To address these challenges and gap in care, we developed an mHealth app screening tool, NeuroScreen, to detect NCI that can be administered by all levels of clinical staff, including lay health workers. ObjectiveThe purpose of this study was to examine sensitivity and specificity of an adapted version of NeuroScreen to detect NCI (as determined by a gold standard neuropsychological test battery administered by a trained research psychometrist) among HIV-infected South Africans when administered by a lay health worker. MethodsA total of 102 HIV-infected black South African adults who had initiated ART at least 12 months prior were administered NeuroScreen and a gold standard neuropsychological test battery in the participants’ choice of language (ie, English or isiXhosa). Three composite z scores were calculated for NeuroScreen: (1) sum of all individual test scores, (2) sum of all individual test scores and error scores from four tests, and (3) sum of four tests (abbreviated version). Global deficit scores were calculated for the gold standard battery where a score of 0.5 or greater indicated the presence of NCI. ResultsThe mean age of participants was 33.31 (SD 7.46) years, most (59.8%, 61/102) had at least 12 years of education, and 81.4% (83/102) of the sample was female. Gold standard test battery results indicated that 26.5% (27/102) of the sample had NCI. Sensitivity and specificity of age-, education-, and sex-adjusted NeuroScreen scores were 81.48% and 74.67% for composite score 1, 81.48% and 81.33% for composite score 2, and 92.59% and 70.67% for composite score 3, respectively. ConclusionsNeuroScreen, a highly automated, easy-to-use, tablet-based screening test to detect NCI among English- and isiXhosa-speaking South African HIV patients demonstrated robust sensitivity and specificity to detect NCI when administered by lay health workers. NeuroScreen could help make screening for NCI more feasible. However, additional research is needed with larger samples and normative test performance data are needed.