Characterising HIV transmission risk among US patients with HIV in care: a cross-sectional study of sexual risk behaviour among individuals with viral load above 1500 copies/mL.

OBJECTIVES: Viral load and sexual risk behaviour contribute to HIV transmission risk. High HIV viral loads present greater transmission risk than transient viral 'blips' above an undetectable level. This paper therefore characterises sexual risk behaviour among patients with HIV in care with viral loads>1500 copies/mL and associated demographic characteristics. METHODS: This cross-sectional study was conducted at six HIV outpatient clinics in USA. The study sample comprises 1315 patients with HIV with a recent viral load >1500 copies/mL. This study sample was drawn from a larger sample of individuals with a recent viral load >1000 copies/mL who completed a computer-assisted self-interview (CASI) regarding sexual risk practices in the last 2 months. The study sample was 32% heterosexual men, 38% men who have sex with men (MSM) and 30% women. RESULTS: Ninety per cent of the sample had their viral load assay within 60 days of the CASI. Thirty-seven per cent reported being sexually active (vaginal or anal intercourse) in the last 2 months. Most of the sexually active participants reported always using condoms (56.9%) or limiting condomless sex to seroconcordant partners (serosorting; 29.2% overall and 42.9% among MSM). Among sexually active participants who reported condomless anal or vaginal sex with an at-risk partner (14%), most had viral loads>10 000 copies/mL (62%). CONCLUSIONS: A relatively small number of patients with HIV in care with viral loads above 1500 copies/mL reported concurrent sexual transmission risk behaviours. Most of the individuals in this small group had markedly elevated viral loads, increasing the probability of transmission. Directing interventions to patients in care with high viral loads and concurrent risk behaviour could strengthen HIV prevention and reduce HIV infections. TRIAL REGISTRATION NUMBER: NCT02044484, completed.

Advancing the Science and Practice of Medication Adherence.

Medication adherence remains a significant unmet challenge for optimizing patient outcomes. Recent advances in the conceptualization, measurement, and support of medication adherence offer fresh opportunities to make a meaningful impact on adherence-related behavior and outcomes. These advances emphasize the multifaceted and dynamic nature of medication adherence, provide novel methods for monitoring medication adherence in clinical care, and articulate a set of multilevel strategies to more effectively improve and sustain medication adherence. Here, we offer recommendations for how clinicians can better engage with, and benefit from, these innovations to improve patient medication adherence and associated treatment outcomes.

Evaluation of a computer-based and counseling support intervention to improve HIV patients' viral loads.

We sought to integrate a brief computer and counseling support intervention into the routine practices of HIV clinics and evaluate effects on patients' viral loads. The project targeted HIV patients in care whose viral loads exceeded 1000 copies/ml at the time of recruitment. Three HIV clinics initiated the intervention immediately, and three other HIV clinics delayed onset for 16 months and served as concurrent controls for evaluating outcomes. The intervention components included a brief computer-based intervention (CBI) focused on antiretroviral therapy adherence; health coaching from project counselors for participants whose viral loads did not improve after doing the CBI; and behavioral screening and palm cards with empowering messages available to all patients at intervention clinics regardless of viral load level. The analytic cohort included 982 patients at intervention clinics and 946 patients at control clinics. Viral loads were assessed at 270 days before recruitment, at time of recruitment, and +270 days later. Results indicated that both the control and intervention groups had significant reductions in viral load, ending with approximately the same viral level at +270 days. There was no evidence that the CBI or the targeted health coaching was responsible for the viral reduction in the intervention group. Results may stem partially from statistical regression to the mean in both groups. Also, clinical providers at control and intervention clinics may have taken action (e.g., conversations with patients, referrals to case managers, adherence counselors, mental health, substance use specialists) to help their patients reduce their viral loads. In conclusion, neither a brief computer-based nor targeted health coaching intervention reduced patients' viral loads beyond levels achieved with standard of care services available to patients at well-resourced HIV clinics.

Factors Associated with Adherence and Concordance Between Measurement Strategies in an HIV Daily Oral Tenofovir/Emtricitibine as Pre-exposure Prophylaxis (Prep) Clinical Trial, Botswana, 2007-2010.

This study examined study product adherence and its determinants in the Botswana oral pre-exposure prophylaxis efficacy trial. Among the 1,219 participants, the mean adherence by pill count and 3-day self-report was 94 % for each. In multivariable models, pill count adherence was significantly associated with adverse events (nausea, dizziness, vomiting) (RR 0.98 95 % CI 0.98-1.00; p = 0.03) and side effect concerns (RR 0.98 95 % CI 0.96-0.99; p = 0.01). Self-reported adherence was significantly associated with having an HIV-positive partner (RR 1.02 95 % CI 1.00-1.04; p = 0.02) and Francistown residence (RR 0.98 95 % CI 0.96, 0.99; p = 0.0001). Detectable drug concentrations showed modest associations with self-report and pill count adherence, and drug levels were higher among those self-reporting 100 % adherence than those reporting <100 %. Most common adherence barriers involved refill delays and other logistic challenges; cellphone alarm reminder use was the most common facilitator.

Adherence to preexposure prophylaxis: current, emerging, and anticipated bases of evidence.

Despite considerable discussion and debate about adherence to preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV), scant data are available that characterize patterns of adherence to open-label PrEP. The current evidence base is instead dominated by research on adherence to placebo-controlled investigational drug by way of drug detection in active-arm participants of large randomized controlled trials (RCTs). Important differences between the context of blinded RCTs and open-label use suggest caution when generalizing from study product adherence to real-world PrEP use. Evidence specific to open-label PrEP adherence is presently sparse but will expand rapidly over the next few years as roll-out, demonstration projects, and more rigorous research collect and present findings. The current evidence bases established cannot yet predict uptake, adherence, or persistence with open-label effective PrEP. Emerging evidence suggests that some cohorts could execute better adherence in open-label use vs placebo-controlled research. Uptake of PrEP is presently slow in the United States; whether this changes as grassroots and community efforts increase awareness of PrEP as an effective HIV prevention option remains to be determined. As recommended by multiple guidelines for PrEP use, all current demonstration projects offer PrEP education and/or counseling. PrEP support approaches generally fall into community-based, technology, monitoring, and integrated sexual health promotion approaches. Developing and implementing research that moves beyond simple correlates of either study product use or open-label PrEP adherence toward more comprehensive models of sociobehavioral and socioecological adherence determinants would greatly accelerate progress. Intervention research is needed to identify effective models of support for open-label PrEP adherence.

Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel.

DESCRIPTION: After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). Adherence to ART is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV. METHODS: A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation. RECOMMENDATIONS: Recommendations are provided for monitoring entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided.

HIV incidence in a multinational cohort of men and transgender women who have sex with men in sub-Saharan Africa: Findings from HPTN 075.

Few studies have assessed HIV incidence in men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA). We assessed HIV incidence and its correlates among MSM and TGW in SSA enrolled in the prospective, multi-country HIV Prevention Trials Network (HPTN) 075 study, conducted from 2015 to 2017. Participants were enrolled at four sites in SSA (Kisumu, Kenya; Blantyre, Malawi; Cape Town and Soweto, South Africa). Eligible participants reported male sex assignment at birth, were 18 to 44 years of age, and had engaged in anal intercourse with a man in the preceding three months. Participation involved five study visits over 12 months. Visits included behavioral assessments and testing for HIV and sexually transmitted infections. Twenty-one of 329 persons acquired HIV during the study [incidence rate: 6.96/100 person-years (PY) (95% CI: 4.3, 10.6)]. Among TGW, HIV incidence was estimated to be 8.4/100 PY (95% CI: 2.3, 21.5). Four participants were found to have acute HIV infection at their first HIV-positive visit. HIV incidence varied among the four study sites, ranging from 1.3/100 PY to 14.4/100 PY. In multivariate longitudinal analysis, factors significantly associated with HIV acquisition were engagement in unprotected receptive anal intercourse [adjusted hazard ratio (AHR) 5.8, 95% confidence interval (CI): 2.4, 14.4] and incident rectal gonorrhea and/or chlamydia (AHR: 2.7, 95% CI: 1.1, 6.8). The higher HIV incidence in Cape Town compared to Blantyre could be explained by the higher prevalence of several risk factors for HIV infection among participants in Cape Town. Annual HIV incidence observed in this study is substantially higher than reported HIV incidence in the general populations in the respective countries and among MSM in the United States. Intensification of HIV prevention efforts for MSM and TGW in SSA is urgently needed.

Applying the Behavioural and Social Sciences Research (BSSR) Functional Framework to HIV Cure Research.

INTRODUCTION: The search for an HIV cure involves important behavioural and social processes that complement the domains of biomedicine. However, the field has yet to tap into the full potential of behavioural and social sciences research (BSSR). In this article, we apply Gaist and Stirratt's BSSR Functional Framework to the field of HIV cure research. DISCUSSION: The BSSR Functional Framework describes four key research domains: (1) basic BSSR (understanding basic behavioural and social factors), (2) elemental BSSR (advancing behavioural and social interventions), (3) supportive BSSR (strengthening biomedically focused clinical trials), and (4) integrative BSSR (building multi-disciplinary combination approaches for real-world implementation). In revisiting and applying the BSSR Functional Framework, we clarify the importance of BSSR in HIV cure research by drawing attention to such things as: how language and communication affect the meaning of "cure" to people living with HIV (PLHIV) and broader communities; how cure affects the identity and social position of PLHIV; counselling and support interventions to address the psychosocial needs and concerns of study participants related to analytical treatment interruptions (ATIs); risk reduction in the course of ATI study participation; motivation, acceptability, and decision-making processes of potential study participants related to different cure strategies; HIV care providers' perceptions and attitudes about their patients' participation in cure research; potential social harms or adverse social events associated with cure research participation; and the scalability of a proven cure strategy in the context of further advances in HIV prevention and treatment. We also discuss the BSSR Functional Framework in the context of ATIs, which involve processes at the confluence of the BSSR domains. CONCLUSIONS: To move HIV cure regimens through the translational research pathway, attention will need to be paid to both biomedical and socio-behavioural elements. BSSR can contribute an improved understanding of the human and social dimensions related to HIV cure research and the eventual application of HIV cure regimens. The BSSR Functional Framework provides a way to identify advances, gaps and opportunities to craft an integrated, multi-disciplinary approach at all stages of cure research to ensure the real-world applicability of any strategy that shows promise.

Mental health and HIV/AIDS: the need for an integrated response.

: Tremendous biomedical advancements in HIV prevention and treatment have led to aspirational efforts to end the HIV epidemic. However, this goal will not be achieved without addressing the significant mental health and substance use problems among people living with HIV (PLWH) and people vulnerable to acquiring HIV. These problems exacerbate the many social and economic barriers to accessing adequate and sustained healthcare, and are among the most challenging barriers to achieving the end of the HIV epidemic. Rates of mental health problems are higher among both people vulnerable to acquiring HIV and PLWH, compared with the general population. Mental health impairments increase risk for HIV acquisition and for negative health outcomes among PLWH at each step in the HIV care continuum. We have the necessary screening tools and efficacious treatments to treat mental health problems among people living with and at risk for HIV. However, we need to prioritize mental health treatment with appropriate resources to address the current mental health screening and treatment gaps. Integration of mental health screening and care into all HIV testing and treatment settings would not only strengthen HIV prevention and care outcomes, but it would additionally improve global access to mental healthcare.

Adherence to biomedical HIV prevention methods: considerations drawn from HIV treatment adherence research.

Biomedical approaches to HIV prevention (eg, microbicides, antiretroviral preexposure prophylaxis) are undergoing clinical trials to test their efficacy. One key consideration emerging from completed trials is the critical role of adherence to the investigational product. Suboptimal product adherence may compromise clinical trial results and ultimately undermine the effectiveness of biomedical prevention methods in any future real-world use. Efforts to strengthen biomedical HIV prevention product adherence can benefit from existing research methodologies, findings, and interventions developed for adherence to HIV treatment. Research on treatment adherence is most relevant to medication-based biomedical prevention strategies, such as antiretroviral preexposure prophylaxis and acyclovir for herpes simplex virus-2. Three areas where HIV treatment adherence literature can inform research on such biomedical prevention strategies are 1) specialized methods for assessing medication adherence, 2) research findings emphasizing social context as an adherence determinant, and 3) promising behavioral interventions to improve adherence.

The Roles of Behavioral and Social Science Research in the Fight Against HIV/AIDS: A Functional Framework.

Landmark advances have been made in HIV/AIDS prevention and treatment. These include proof-of-concept and public health implementation of preexposure prophylaxis and "treatment as prevention" to reduce HIV transmission as well as definitive evidence of the clinical gain from early antiretroviral treatment initiation. Significant progress has been made in understanding and addressing the social contexts and behavioral factors that impact HIV prevention, care, and treatment interventions. These include facilitating uptake of testing and counseling, developing technology-based interventions that increase viral suppression, reducing HIV/AIDS-related stigma, and addressing other sociobehavioral and structural barriers to care and treatment. This evolving landscape provides an important juncture to assess current and future directions for HIV/AIDS behavioral and social science research (BSSR). We propose a functional framework for HIV/AIDS-related BSSR, highlighting 4 primary BSSR domains: (1) understanding vulnerable populations and contexts of risk ("Basic BSSR"); (2) improving behavioral and social factor approaches to risk reduction, prevention, and care ("Elemental BSSR"); (3) strengthening the design and outcomes of biomedically focused research in HIV/AIDS treatment and prevention ("Supportive BSSR"); and (4) contributing building blocks to integrated HIV/AIDS prevention and treatment approaches ("Integrative BSSR"). These domains and their resulting confluence at the highest level underscore how fundamental and essential BSSR is to current and future efforts to prevent, treat, and cure HIV/AIDS.

Improving antiretroviral therapy adherence in resource-limited settings at scale: a discussion of interventions and recommendations.

Introduction: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. Methods: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. Conclusions: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS.

Single Viral Load Measurements Overestimate Stable Viral Suppression Among HIV Patients in Care: Clinical and Public Health Implications.

BACKGROUND: The HIV continuum of care paradigm uses a single viral load test per patient to estimate the prevalence of viral suppression. We compared this single-value approach with approaches that used multiple viral load tests to examine the stability of suppression. METHODS: The retrospective analysis included HIV patients who had at least 2 viral load tests during a 12-month observation period. We assessed the (1) percent with suppressed viral load (<200 copies/mL) based on a single test during observation, (2) percent with suppressed viral loads on all tests during observation, (3) percent who maintained viral suppression among patients whose first observed viral load was suppressed, and (4) change in viral suppression status comparing first with last measurement occasions. Prevalence ratios compared demographic and clinical subgroups. RESULTS: Of 10,942 patients, 78.5% had a suppressed viral load based on a single test, whereas 65.9% were virally suppressed on all tests during observation. Of patients whose first observed viral load was suppressed, 87.5% were suppressed on all subsequent tests in the next 12 months. More patients exhibited improving status (13.3% went from unsuppressed to suppressed) than worsening status (5.6% went from suppressed to unsuppressed). Stable suppression was less likely among women, younger patients, black patients, those recently diagnosed with HIV, and those who missed ≥1 scheduled clinic visits. CONCLUSIONS: Using single viral load measurements overestimated the percent of HIV patients with stable suppressed viral load by 16% (relative difference). Targeted clinical interventions are needed to increase the percent of patients with stable suppression.

Couple-focused support to improve HIV medication adherence: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems. DESIGN: A randomized controlled trial (SMART Couples Study) conducted between August 2000 and January 2004. SETTING: Two HIV/AIDS outpatient clinics in New York City. PARTICIPANTS: Heterosexual and homosexual HIV-serodiscordant couples (n = 215) in which the HIV-seropositive partner had < 80% adherence at baseline. The sample was predominantly lower-income racial/ethnic minorities. INTERVENTION: Participants were randomly assigned to a four-session couple-focused adherence intervention or usual care. The intervention consisted of education about treatment and adherence, identifying adherence barriers, developing communication and problem-solving strategies, optimizing partner support, and building confidence for optimal adherence. OUTCOME MEASURES: Medication adherence at week 8 (2 weeks after the intervention) compared with baseline, assessed with a Medication Event Monitoring System cap. RESULTS: Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken (76% versus 60%) or doses taken within specified time parameters (58% versus 35%). Also, participants in the intervention arm were significantly more likely to achieve high levels of adherence (> 80%, > 90%, or > 95%) when compared with controls. However, in most cases, effects diminished with time, as seen at follow-up at 3 and 6 months. CONCLUSION: The SMART Couples program significantly improved medication adherence over usual care, although the level of improved adherence, for many participants, was still suboptimal and the effect was attenuated over time.

Seroconcordant sexual partnerings of HIV-seropositive men who have sex with men.

OBJECTIVES: To describe the sexual behaviors of HIV-positive men with their seroconcordant partners and to determine the factors associated with unprotected anal intercourse (UAI) in these sexual partnerings. METHODS: The data were drawn from the baseline assessment of a randomized controlled intervention study of 1168 HIV-positive men who have sex with men recruited from mainstream gay venues, AIDS service organizations, and public/commercial sex environments. RESULTS: Of the 1168 men, 596 engaged in sexual experiences with other HIV-positive men, and 371 of the 596 (62%) practised UAI with their seroconcordant partners. Those who engaged in UAI expressed less self-evaluation with regard to their unsafe sexual practices, had higher levels of hedonism associated with unsafe sex, and were more likely both to inject recreation drugs and use methamphetamine in particular. Furthermore, these participants expressed less concern with regard to HIV re-infection, infection with other sexually transmitted infections, and the transmission of pathogens causing opportunistic infections. CONCLUSION: Our findings suggest that at least three sets of factors predispose HIV-positive men to engage in unsafe anal sexual behaviors with their concordant partners: a decreased belief that infection with other pathogens or re-infection with HIV present health problems; less evaluation of sexual activities and behaviors; more hedonistic expectations of sex and higher levels of sexual compulsivity, as well as recreational drug use with and without sex.

Self-report measures of medication adherence behavior: recommendations on optimal use.

Medication adherence plays an important role in optimizing the outcomes of many treatment and preventive regimens in chronic illness. Self-report is the most common method for assessing adherence behavior in research and clinical care, but there are questions about its validity and precision. The NIH Adherence Network assembled a panel of adherence research experts working across various chronic illnesses to review self-report medication adherence measures and research on their validity. Self-report medication adherence measures vary substantially in their question phrasing, recall periods, and response items. Self-reports tend to overestimate adherence behavior compared with other assessment methods and generally have high specificity but low sensitivity. Most evidence indicates that self-report adherence measures show moderate correspondence to other adherence measures and can significantly predict clinical outcomes. The quality of self-report adherence measures may be enhanced through efforts to use validated scales, assess the proper construct, improve estimation, facilitate recall, reduce social desirability bias, and employ technologic delivery. Self-report medication adherence measures can provide actionable information despite their limitations. They are preferred when speed, efficiency, and low-cost measures are required, as is often the case in clinical care.