Using context-specific evidence to inform resource-stratified cancer guidelines: A call for a new approach.

Clinical practice guidelines are widely used in oncology to guide clinical decision making and inform health policy and planning. In recent years, the National Comprehensive Cancer Network and the American Society of Clinical Oncology, as well as other international groups, have developed resource-stratified guidelines to guide clinicians and policymakers on cancer diagnosis and management in settings with various levels of resource constraints. Current methods for developing resource-stratified guidelines rely heavily on supporting evidence originating from high-income countries. In this commentary, the authors discuss limitations of the existing methods to develop resource-stratified guidelines and offer perspective on ways to strengthen the guidelines and their evidence base. Pulling from conceptual frameworks in the health policy domain, the authors outline a more inclusive approach to evidence synthesis that seeks to integrate the growing volume of cancer research emerging from low- and middle-income countries. The authors also introduce a revised evidence framework that provides transparency into the generalizability of evidence within the guidelines. These changes have the potential to enhance resource-stratified guidelines and bring us one step closer to the goal of evidence-based guidelines that are appropriate for diverse settings and unique patient populations across the world.

Hoping to Adhere? Examining the Relationship Between Hope and Pre-exposure Prophylaxis Willingness, Adherence, and Persistence Among Young Women in South Africa and Zimbabwe (HPTN 082).

Hope is a powerful psychological construct which is linked to positive health. Greater hope is associated with improved antiretroviral therapy adherence; however, less is known about the impact of hope on oral pre-exposure prophylaxis (PrEP) outcomes. HIV Prevention Trials Network 082, was an open-label PrEP study among young women (ages 16-25) in South Africa and Zimbabwe. Hope was measured at baseline and follow-up using a subset of the Hope for the Future Scale (score range 6-24) and PrEP willingness was measured using a subscale of the HIV Prevention Readiness Measure (score range 6-30). Intracellular tenofovir-diphosphate (TFV-DP) concentrations were obtained from dried blood spot samples at weeks 13, 26, and 52; high PrEP adherence was defined as TFV-DP concentrations ≥ 700 fmol/punch. Persistence was defined as TFV-DP > 16 fmol/punch at weeks 26 and 52. Linear regression and generalized estimating equations were used to assess the relationship between hope and PrEP willingness, adherence, and persistence. The median age of participants (n = 432) was 21 years (interquartile range [IQR]: 19-22). The mean hope score at baseline was 21.0 (SD = 3.4). Although hope was positively associated with PrEP willingness (ß = 0.22, 95% CI 0.15, 0.37), it was not associated with high PrEP adherence (aRR = 1.00, 95% CI 0.96, 1.05), or persistence at follow-up (aRR = 1.02, 95% CI 0.99, 1.05). While cultivating hope may be an important strategy in building willingness to take oral PrEP, it may not be enough to sustain PrEP adherence or persistence.

Engagement Along the PrEP Care Continuum Among Men Who Have Sex with Men in China: A Systematic Review and Meta-analysis.

Pre-exposure prophylaxis (PrEP), including daily oral, on-demand, and long-acting injectable (LAI), is a promising HIV prevention intervention for men who have sex with men (MSM). We conducted a systematic review on engagement with the PrEP continuum among MSM in China. A total of 756 studies were initially identified and 36 studies were included (N = 26,021). In the 20 studies (N = 13,886) examining PrEP awareness, 32.4% (95% CI: 25.1-40.7) of MSM were aware of PrEP. In the 25 studies (N = 18,587) examining willingness, 54.5% (95% CI: 41.9-66.5) MSM indicated they were willing to use PrEP. The pooled prevalence of PrEP uptake from 9 studies (N = 6,575) was 4.9% (95% CI: 1.4-15.8%), while pooled estimates of adequate adherence from five studies (N = 2,344) among MSM on PrEP was 40.7% (95% CI: 20.0-65.2%). Subgroup analyses suggested studies conducted after 2015 (versus before) tended to report higher awareness and uptake. Awareness was highest for daily oral PrEP, followed by on-demand, and LAI PrEP; willingness to use was highest for LAI PrEP. The operationalization of willingness and adherence constructs varied across studies and complicated the interpretation of pooled estimates. This review revealed gaps in the PrEP care continuum among MSM in China, with relatively low awareness and uptake (in contrast to willingness and adherence) as the major potential barriers to widespread implementation and the need for a unified approach to defining and measuring PrEP outcomes.

Acceptability of an automated directly observed therapy (DOT) application for PrEP adherence support among young men who have sex with men: a qualitative exploration.

Pre-exposure prophylaxis (PrEP) adherence remains a challenge among young men who have sex with men (MSM). We developed and tested a smartphone application ("app"), "DOT Diary", which combines automated directly observed therapy (DOT) with information about PrEP protection levels, pill-taking reminders, a sexual behavior diary, and a PrEP dosing calendar. To contextualize trial results, we qualitatively explored participants' app experiences. The trial enrolled 100 young MSM in San Francisco and Atlanta. Participants were randomized 2:1 to DOT Diary versus standard-of-care and followed for 24 weeks. Interviews were conducted with 24 intervention participants. Data were analyzed using a memo-writing approach. Most expressed overall satisfaction with the app ("it was good for its purpose"), despite concerns about technical glitches. The most popular app features were the monthly calendar showing days PrEP was taken and information about level of protection based on pills taken. The DOT component helped participants establish PrEP routines. The reminders were "annoying but effective" at motivating dosing. Opinions about the sexual behavior diary varied. Overall, DOT Diary was acceptable; participants were willing to use it daily to record pill-taking. Critical components included the information about PrEP protection levels and calendar, while others may be modified to improve future success.Trial registration: ClinicalTrials.gov identifier: NCT03771638.

An Application of Evidence-Based Approaches to Engage Young People in the Design of a Global Mental Health Databank.

INTRODUCTION: Engaging youth in mental health research and intervention design has the potential to improve their relevance and effectiveness. Frameworks like Roger Hart's ladder of participation, Shier's pathways to participation and Lundy's voice and influence model aim to balance power between youth and adults. Hart's Ladder, specifically, is underutilized in global mental health research, presenting new opportunities to examine power dynamics across various contexts. Drawing on Hart's ladder, our study examined youth engagement in mental health research across high- and middle-income countries using Internet-based technologies, evaluating youth involvement in decision-making and presenting research stages that illustrate these engagements. METHODS: We conducted a directed content analysis of youth engagement in the study using primary data from project documents, weekly AirTable updates and discussions and interviews with youth and the research consortium. Using Hart's Ladder as a framework, we describe youth engagement along rungs throughout different research stages: cross-cutting research process, onboarding, formative research and quantitative and qualitative study designs. RESULTS: Youth engagement in the MindKind study fluctuated between Rung 4 ('Assign, but informed') and Rung 7 ('Youth initiated and directed') on Hart's Ladder. Engagement was minimal in the early project stages as project structures and goals were defined, with some youth feeling that their experiences were underutilized and many decisions being adult-led. Communication challenges and structural constraints, like tight timelines and limited budget, hindered youth engagement in highest ladder rungs. Despite these obstacles, youth engagement increased, particularly in developing recruitment strategies and in shaping data governance models and the qualitative study design. Youth helped refine research tools and protocols, resulting in moderate to substantial engagement in the later research stages. CONCLUSION: Our findings emphasize the value of youth-adult partnerships, which offer promise in amplifying voices and nurturing skills, leadership and inclusiveness of young people. Youth engagement in project decision-making progressed from lower to higher rungs on Hart's Ladder over time; however, this was not linear. Effective youth engagement requires dynamic strategies, transparent communication and mutual respect, shaping outcomes that authentically reflect diverse perspectives and mental health experiences. PATIENT OR PUBLIC CONTRIBUTION: There was substantial patient and public involvement in this study. This paper reports findings on youth engagement conducted with 35 young people from India, South Africa and the United Kingdom, all of whom had lived experience of mental health challenges. Youth engagement in the MindKind study was coordinated and led by three professional youth advisors (PYAs) in these contexts, who were also young people with lived experience of mental health challenges. Each of the three study sites embedded a full-time, community-based PYA within their study team to inform all aspects of the research project, including the development of informational materials and the facilitation of Young People's Advisory Group (YPAG) sessions referenced in this paper. Each PYA also consulted with a site-specific YPAG that met bi-monthly throughout the project, shaping the formation of study materials and serving as a test group in both the quantitative and qualitative studies. Youth participants in this study also contributed extensively, engaging in data collection and manuscript writing. The following youth advisory panels members (J.B., L.B., D.O.J., M.V.) and all PYAs (E.B., S.R., R.S.) in the MindKind study contributed to the writing of this manuscript and are acknowledged as co-authors.

Acceptability Assessment in HIV Prevention and Treatment Intervention and Service Delivery Research: A Systematic Review and Qualitative Analysis.

We reviewed the literature on the assessment of acceptability of HIV prevention and treatment interventions and service delivery strategies. Following PRISMA guidelines, we screened 601 studies published from 2015 to 2020 and included 217 in our review. Of 384 excluded studies, 21% were excluded because they relied on retention as the sole acceptability indicator. Of 217 included studies, only 16% were rated at our highest tier of methodological rigor. Operational definitions of acceptability varied widely and failed to comprehensively represent the suggested constructs in current acceptability frameworks. Overall, 25 studies used formal quantitative assessments (including four adapted measures used in prior studies) and six incorporated frameworks of acceptability. Findings suggest acceptability assessment in recent HIV intervention and service delivery research lacks harmonization and rigor. We offer guidelines for best practices and future research, which are timely and critical in this era of informed choice and novel options for HIV prevention and treatment.

A novel "HIV salience and Perception" scale is associated with PrEP dispensing and adherence among adolescent girls and young women in Kampala, Uganda.

Low perceived HIV risk is a barrier to effective pre-exposure prophylaxis (PrEP) use among African adolescent girls and young women (AGYW). Single-item risk perception measures are stigmatizing and alienating to AGYW and may not predict PrEP use. There is a need for a tool capturing domains of perceived HIV risk and salience that align with PrEP use among AGYW. This HIV PrEP study was conducted in Kampala, Uganda. We developed and piloted the 9-item "HIV Salience and Perception" (HPS) scale (range: 9-36); higher scores indicate beliefs of higher vulnerability to HIV. We administered the scale to Ugandan AGYW participating in an ongoing cohort study at enrollment, one, three and six months. PrEP dispensing was measured quarterly and adherence was measured daily via Wisepill (high adherence: ≥80% of expected pill bottle openings). We assessed scale performance and used generalized estimating equations to determine associations between scale score and PrEP use. Among 499 AGYW, 54.1% of our sample was ≥ 20 years (range:16-25). The median HPS score was 18 (range:8-33; α = 0.77). Higher score was associated with PrEP dispensing (aRR = 1.07 per point increase; 95% CI = 1.01-1.13; p-value = 0.02) in the overall cohort and among only those ≥ 20 years (aRR = 1.10; 95% CI = 1.03-1.19; p-value = 0.01). We did not observe an association between scale score and PrEP adherence. AGYW scoring higher on a novel HPS scale were more likely to initiate and obtain PrEP refills through 6 months. This scale may capture drivers of PrEP dispensing and could inform PrEP delivery and counseling for AGYW.

Perinatal Depressive Symptoms and Viral Non-suppression Among a Prospective Cohort of Pregnant Women Living with HIV in Nigeria, Kenya, Uganda, and Tanzania.

Depression is common during pregnancy and is associated with reduced adherence to HIV-related care, though little is known about perinatal trajectories of depression and viral suppression among women living with HIV (WLHV) in sub-Saharan Africa. We sought to assess any association between perinatal depressive symptoms and viral non-suppression among WLWH. Depressive symptomatology and viral load data were collected every 6 months from WLWH enrolled in the African Cohort Study (AFRICOS; January 2013-February 2020). Generalized estimating equations modeled associations between depressive symptoms [Center for Epidemiological Studies Depression (CES-D) ≥ 16] and viral non-suppression. Of 1722 WLWH, 248 (14.4%) had at least one pregnancy (291 total) and for 61 pregnancies (21.0%), women reported depressive symptoms (13.4% pre-conception, 7.6% pregnancy, 5.5% one-year postpartum). Depressive symptomatology was associated with increased odds of viral non-suppression (aOR 2.2; 95% CI 1.2-4.0, p = 0.011). Identification and treatment of depression among women with HIV may improve HIV outcomes for mothers.

Multi-level Interventions to Promote Oral Pre-exposure Prophylaxis Use Among Adolescent Girls and Young Women: a Review of Recent Research.

PURPOSE OF REVIEW: This review summarizes interventions to promote HIV pre-exposure prophylaxis (PrEP) use among adolescent girls and young women (AGYW) in HIV endemic settings, while also highlighting gaps in our current measures of PrEP intervention success. RECENT FINDINGS: AGYW report challenges with PrEP use, although the field is currently grappling with defining metrics of optimal PrEP use applicable for AGYW with dynamic HIV prevention needs. Ongoing studies are exploring multilevel interventions to address barriers to PrEP use for AGYW. At the individual and interpersonal levels, mHealth, drug-level feedback, adherence counseling, peer groups, and PrEP decision-support interventions are acceptable and feasible for AGYW although limited effectiveness data are available. At the health facility and community levels, PrEP demand creation, modified PrEP refill schedules, and integrated PrEP and reproductive health services are also promising options to support PrEP use for AGYW. As PrEP delivery continues to expand, improved metrics of success and evidence on the effectiveness of multi-level adherence support interventions are needed to maximize the impact of PrEP for AGYW in HIV endemic settings. We present case studies of these intervention approaches but limited data are currently available on the effectiveness of these approaches. We will look toward forthcoming study results on the impact of PrEP interventions, including mHealth, drug-level feedback and other enhanced counseling, peer support, decision-support tools, PrEP demand creation, modified refills, and integrated service delivery, to determine the ideal package of PrEP support approaches for AGYW.

Use of fertility awareness methods as a component of safer conception for women in HIV-serodifferent relationships in Kenya.

BACKGROUND: For couples affected by HIV, and serodifferent couples in particular, pregnancy desire is often juxtaposed against the risk of HIV transmission between the couple and the potential neonate leading to thinking about measures to minimize risk of HIV transmission. We assess the use of fertility awareness methods [FAM] and evaluate the drivers of alignment between indicators of fertility and sexual behavior among HIV-serodifferent couples desiring pregnancy. METHODS: HIV-serodifferent couples from Thika, Kenya were enrolled into an open-label pilot evaluation of safer conception strategies. Women responded to daily 7-item short message service [SMS] surveys on FAM and sexual activity. Menstrual cycles were categorized as having condomless sex aligned, not aligned, or partially aligned to the predicted peak fertility. We used binomial logit models with generalized estimating equations to assess alignment between condomless sex during peak fertility days and FAM results. We used Cox proportional hazards to compare pregnancy incidence among months with sex and peak fertility aligned and mis-aligned. RESULTS: A total of 6929 SMS surveys across 252 menstrual cycles of 65 women were included. Reporting "sticky" cervical mucus (adjusted odds ratio [aOR]: 2.25, 95% confidence interval [95% CI]: 1.30, 3.90) and positive ovulation prediction kit [OPK] result (aOR: 2.07, 95% CI: 1.11, 3.86) were associated with increased likelihood of alignment of condomless sex during peak fertility. Pregnancy incidence was statistically similar among periods with sex aligned and not aligned with peak fertility. CONCLUSIONS: Among women engaged in a comprehensive safer conception program, a moderate percentage of women aligned condomless sex and predicted peak fertility days at least once. While FAM, particularly cervical mucus and OPK, are an inexpensive option for couples to consider using as a component of their safer conception strategies, antiretroviral-based strategies remain important to minimize risk.

Alcohol Use and Antiretroviral Therapy Non-Adherence Among Adults Living with HIV/AIDS in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Antiretroviral therapy (ART) is efficacious in improving clinical outcomes among people living with HIV (PLWH) and reducing HIV transmission when taken regularly. Research examining modifiable factors associated with ART non-adherence is critical for informing novel intervention development in settings with high HIV prevalence. Alcohol use has been linked with ART non-adherence in studies in sub-Saharan Africa; however, no review has pooled estimates across studies. We reviewed studies of alcohol use and ART non-adherence conducted in sub-Saharan Africa. We searched PubMed, CINAHL, EMBASE, and PsycINFO through August 2019 with terms related to ART non-adherence, alcohol use, and sub-Saharan Africa. One author reviewed titles/abstracts (n = 754) and two authors reviewed full texts (n = 308) for inclusion. Discrepancies were resolved by group consensus. Studies were retained if they quantitatively measured associations between alcohol use and ART non-adherence or viral non-suppression. We defined ART non-adherence using the definitions from each parent study (e.g., patients with > 5% missed ART doses during the previous four, seven or 30 days were considered non-adherent). A random effects meta-analysis was conducted to pool associations and we conducted additional analyses to assess between-study heterogeneity and publication bias and sensitivity analyses to determine robustness of our results when considering only certain study designs, alcohol use or ART scales, or studies that used viral non-suppression as their primary outcome. Of 56 articles meeting our inclusion criteria, 32 articles were included in the meta-analysis. All studies measured alcohol use via self-report. ART non-adherence was assessed using self-report, pill counts, or pharmacy records and definition of non-adherence varied depending on the measure used. Individuals who used alcohol had twice the odds of ART non-adherence compared with those who did not use alcohol (34% non-adherence among alcohol users vs. 18% among non-users; pooled odds ratio: 2.25; 95% confidence interval: 1.87-2.69; p < 0.001). We found evidence of a high degree of heterogeneity between studies (Cochrane Q statistic: 382.84, p< 0.001; I2 proportion: 91.9%) and evidence of publication bias. However, the magnitude of our pooled odds ratio was consistent across a number of sensitivity analyses to account for heterogeneity and publication bias. In a secondary analysis with studies using viral non-suppression as their primary outcome, we also estimated a statistically significant pooled effect of alcohol use on viral non-suppression (pooled odds ratio: 2.47; 95% confidence interval: 1.58-3.87). Evidence suggests alcohol use is associated with ART non-adherence in Sub-Saharan Africa, potentially hindering achievement of the UNAIDS 90-90-90 HIV treatment targets.

The Effect of Depression on Adherence to HIV Pre-exposure Prophylaxis Among High-Risk South African Women in HPTN 067/ADAPT.

Oral pre-exposure prophylaxis (PrEP) is highly efficacious but low adherence undermines effectiveness. Depression, common in African women, may be a barrier to consistent PrEP use. We aimed to assess the relationship between depression, psychosocial mediators, and PrEP adherence among South African women. We analyzed data from 174 South African women in HPTN 067, an open-label oral PrEP trial conducted from 2011 to 2013. Participants were followed for 24 weeks. PrEP adherence was measured via Wisepill™ and weekly self-report interview data. We considered participants "adherent" at week 24 if Wisepill™ and interviews indicated that ≥ 80% of expected doses were taken in the prior month. Elevated depressive symptoms were assessed using the 20-item Center for Epidemiological Studies-Depression (CES-D) scale. We used marginal structural models to estimate the effect of elevated symptoms at baseline on PrEP adherence at week 24 and to assess whether the direct effect changed meaningfully after accounting for mediating effects of stigma, social support, and PrEP optimism. High PrEP adherence occurred less often among women with elevated depressive symptoms (N = 35; 44.3%) compared with those without (N = 52; 54.7%; adjusted relative risk [aRR]: 0.79; 95% confidence interval [CI] 0.63-0.99). The effect of elevated depressive symptoms on PrEP adherence persisted in models accounting for the mediating influence of stigma (aRR: 0.74; 95% CI 0.51-0.97) and PrEP optimism (aRR: 0.75; 95% CI 0.55-0.99). We also found a direct effect of similar magnitude and direction when accounting for social support as the mediating variable, although this adjusted relative risk estimate was not statistically significant (aRR: 0.77; 95% CI 0.57-1.03). Depressive symptoms were common and associated with lower PrEP adherence among South African women. Future work is needed to determine whether depression services integrated with PrEP delivery could improve PrEP effectiveness among African women.

Cognitive testing of the PHQ-9 for depression screening among pregnant and postpartum women in Kenya.

BACKGROUND: African women face high rates of depression, particularly during pregnancy or postpartum or after a recent HIV diagnosis. The Patient Health Questionnaire-9 (PHQ-9) depression screening tool has been quantitatively validated and extensively used to identify depression and link individuals to care. However, qualitative work is necessary to identify important opportunities to improve PHQ-9 question comprehension and performance among Kenyan women. METHODS: We administered the Kiswahili or English PHQ-9 (based on preference) to 29 pregnant and postpartum women in Thika, Kenya. Following administration, we conducted cognitive interviews with a purposive sample of 20 women. We used analytic memos and data matrices to identify themes around scale acceptability, comprehension, and decision and response processes. RESULTS: Most participants preferred to answer the PHQ-9 in Kiswahili (N = 15; 52%). Among the 20 interview participants, 12 (60%) had scores ≥5, indicating depressive symptoms. Overall, participants found the scale acceptable as an interviewer-administered tool. Participants reported few problems related to comprehension but had difficulty answering items not relevant to their lives (e.g., "watching television") and double-barreled items (e.g., "poor appetite or overeating"). They were hesitant to endorse items related to "duties as a wife and mother" and suicidal ideation. Most participants had difficulty distinguishing between response options of "several days" and "more than half the days". CONCLUSIONS: We detected several problems related to PHQ-9 comprehension, decision processes, and response processes. We provide recommended changes to instructions and item wording to improve PHQ-9 validity among Kenyan women.

High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Bacterial vaginosis (BV) is the most common vaginal infection among women of reproductive age and is associated with important adverse health outcomes. Estimates of the burden of BV and associated costs are needed to inform research priorities. METHODS: We conducted a systematic review and meta-analysis of global BV prevalence among reproductive-aged women in the general population. We searched PubMed and Embase and used random effects models to estimate BV prevalence by global regions. We estimated the direct medical costs of treating symptomatic BV. Assuming a causal relationship, we also estimated the potential costs of BV-associated preterm births and human immunodeficiency virus cases in the United States. RESULTS: General population prevalence of BV is high globally, ranging from 23% to 29% across regions (Europe and Central Asia, 23%; East Asia and Pacific, 24%; Latin America and Caribbean, 24%; Middle East and North Africa, 25%; sub-Saharan Africa, 25%; North America, 27%; South Asia, 29%). Within North America, black and Hispanic women have significantly higher (33% and 31%, respectively) prevalence compared with other racial groups (white, 23%; Asian, 11%; P < 0.01). The estimated annual global economic burden of treating symptomatic BV is US $4.8 (95% confidence interval, $3.7-$6.1) billion. The US economic burden of BV is nearly tripled when including costs of BV-associated preterm births and human immunodeficiency virus cases. CONCLUSIONS: The BV prevalence is high globally, with a concomitant high economic burden and marked racial disparities in prevalence. Research to determine the etiology of BV and corresponding prevention and sustainable treatment strategies are urgently needed to reduce the burden of BV among women. Additionally, the exceptionally high cost of BV-associated sequelae highlights the need for research to understand potential causal linkages between BV and adverse health outcomes.

Associations Between Anxiety and Adherence to Antiretroviral Medications in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

Untreated mental health disorders among people living with HIV (PLHIV) may prevent low- and middle-income countries (LMICs) from achieving the UNAIDS 90-90-90 targets. Anxiety disorders may be associated with decreased adherence to antiretroviral therapy (ART). We sought to review and meta-analyze studies estimating associations between anxiety and ART adherence in LMICs. We searched PubMed, PsychINFO, CINAHL and EMBASE for relevant studies published before July 18, 2018. We defined anxiety as reported anxiety scores from screening questionnaires or having a clinical diagnosis of an anxiety disorder, and poor ART adherence as missed doses, poor visit attendance, or scores from structured adherence questionnaires. We used a random effects model to conduct a meta-analysis for calculating a pooled odds ratio, and conducted sensitivity analyses by time on ART, anxiety evaluation method, and study region. From 472 screened manuscripts, thirteen studies met our inclusion criteria. Eleven studies were included in the meta-analysis. PLHIV who reported anxiety had 59% higher odds of poor ART adherence compared with those who did not report anxiety disorder (pooled odds ratio [pOR]: 1.59, 95% confidence interval [CI] 1.29-1.96, p < 0.001). When excluding PLHIV who initiated ART within 6 months, reported anxiety remained strongly associated with poor ART adherence (pOR: 1.61, 95% CI 1.18-2.20, p = 0.003). Among PLHIV in LMICs, reported anxiety was associated with poor ART adherence. This association persisted after the ART initiation period. Increased resources for mental health may be important for achieving virologic suppression in LMICs.

Implementation of eHealth Interventions Across the HIV Care Cascade: a Review of Recent Research.

PURPOSE OF REVIEW: We review recent implementation science focusing on eHealth interventions to improve outcomes along the HIV care cascade. We highlight several gaps in the eHealth implementation literature and propose areas for future study. RECENT FINDINGS: We identified 17 studies conducted in North America, Europe, and sub-Saharan Africa assessing the acceptability, appropriateness, adoption, cost, feasibility, fidelity, penetration, or sustainability of eHealth interventions targeting the HIV care cascade. Most interventions used SMS messages to improve cascade outcomes. Feasibility research has demonstrated the importance of adaptability for intervention scale-up and delivery. Key gaps in the literature remain related to predictors of the adoption of eHealth interventions by health facilities and staff. In addition, no studies explored sustainability and few used theoretical frameworks for implementation research or validated measures of implementation outcomes. We propose next steps for the future of eHealth implementation research to inform the delivery, scale-up, and maintenance of eHealth interventions in the real world.

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women.

PURPOSE OF REVIEW: This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. RECENT FINDINGS: We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

HIV-Risk Behaviors and Social Support Among Men and Women Attending Alcohol-Serving Venues in South Africa: Implications for HIV Prevention.

Alcohol use is associated with increased HIV-risk behaviors, including unprotected sex and number of sex partners. Alcohol-serving venues can be places to engage in HIV-related sexual risk behaviors, but are also important sites of social support for patrons, which may mitigate risks. We sought to examine the relationship between alcohol-serving venue attendance, social support, and HIV-related sexual risk behavior, by gender, in South Africa. Adult patrons (n = 496) were recruited from six alcohol-serving venues and completed surveys assessing frequency of venue attendance, venue-based social support, and recent sexual behaviors. Generalized estimating equations tested associations between daily venue attendance, social support, and sexual behaviors, separately by gender. Interaction effects between daily attendance and social support were assessed. Models were adjusted for venue, age, education, and ethnicity. Daily attendance at venues was similar across genders and was associated with HIV-related risk behaviors, but the strength and direction of associations differed by gender. Among women, daily attendance was associated with greater number of partners and higher proportion of unprotected sex. Social support was a significant moderator, with more support decreasing the strength of the relationship between attendance and risk. Among men, daily attendance was associated with a lower proportion of unprotected sex; no interaction effects were found for attendance and social support. Frequent venue attendance is associated with additional HIV-related risks for women, but this risk is mitigated by social support in venues. These results were not seen for men. Successful HIV interventions in alcohol-serving venues should address the gendered context of social support and sexual risk behavior.

Depression and ART Initiation Among HIV Serodiscordant Couples in Kenya and Uganda.

Depression is a known barrier for antiretroviral therapy (ART) adherence, but less is understood about its effects on ART initiation. We followed 1013 HIV-infected individuals participating in the Partners Demonstration Project, an open-label study of integrated pre-exposure prophylaxis (PrEP) and ART delivery for HIV serodiscordant couples in Kenya and Uganda. Associations between depression, measured annually with the Hopkins Symptoms Checklist-Depression (HSCL-D), and ART initiation were assessed with Cox proportional hazards regression. At enrollment, 162 participants (16.0%) reported symptoms consistent with probable depression, defined by a HSCL-D mean score >1.75, and this proportion decreased during study follow-up (6.7 and 3.6% at 12- and 24-months, respectively; p value < 0.001). Greater depressive symptom severity was associated with a greater likelihood of ART initiation overall (adjusted hazard ratio [aHR] 1.32, 95% CI 1.01-1.73) and among participants with CD4 count ≤ 350 cells/µl (aHR 1.30, 95% CI 1.01-1.67). Depression decreased 6 months after ART initiation (adjusted odds ratio [aOR] 0.34, 95% CI 0.23-0.51). Among East African HIV-infected persons in HIV serodiscordant couples, depression was not a barrier to ART initiation. ART initiation was associated with improved depressive symptoms in this setting.

Adherence during antiviral treatment regimens for chronic hepatitis C: a qualitative study of patient-reported facilitators and barriers.

GOALS: To understand patients' perceptions of factors which facilitate and hinder adherence to inform adherence-enhancing interventions. BACKGROUND: Adherence to antiviral therapy for hepatitis C viral infection is critical to achieving a sustained virological response. However, persistence with and adherence to antiviral regimens can pose challenges for patients that interfere with sustained virological response. STUDY: A qualitative analysis of 21 semistructured patient interviews using open-ended questions and specific follow-up probes was conducted. Interviews were audio-recorded, transcribed, and content-analyzed iteratively to determine frequent and salient themes. RESULTS: Three broad themes emerged: (1) missing doses and dose-timing errors; (2) facilitators of adherence; and (3) barriers to adherence. Open-ended questioning revealed few dose-timing deviations, but more specific probes uncovered several more occurrences of delays in dosing. Facilitators of adherence fell into 2 broad categories: (a) patient knowledge and motivation; and (b) practical behavioral strategies and routines. Facilitators were noted post hoc to be consistent with the Information-Motivation-Behavioral Skills Model of Adherence. Barriers to adherence involved changes in daily routine, being preoccupied with family or work responsibilities, and sleeping through dosing times. A few patients reported skipping doses due to side effects. Patients with previous hepatitis C virus treatment experience may have fewer dose-timing errors. Finally, a high level of anxiety among some patients was discovered regarding dosing errors. Emotional and informational support from clinical and research staff was key to assuaging patient fears. CONCLUSION: This qualitative study improves our understanding of patients' perspectives regarding adhering to hepatitis C treatment and can lead to the development of adherence-enhancing interventions.