Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions.

BACKGROUND: The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. METHODS: Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. RESULTS: Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. CONCLUSION: Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs.

How Presentation of Drug Detection Results Changed Reports of Product Adherence in South Africa, Uganda and Zimbabwe.

Accurate estimates of study product use are critical to understanding and addressing adherence challenges in HIV prevention trials. The VOICE trial exposed a significant gap between self-reported adherence and drug detection. The VOICE-D qualitative study was designed to better understand non-adherence during VOICE, and was conducted in 2 stages: before (stage 1) and after (stage 2) drug detection results were provided to participants. Transcripts from 44 women who participated in both stages were analysed to understand the effect of presenting drug detection data on narratives of product use. Thirty-six women reported high adherence in stage 1, yet admitted non-use in stage 2, three reported high adherence in both stages (contrary to their drug detection results) and five had consistent responses across both stages and drug results. Presenting objective measures of use may facilitate more accurate product use reporting and should be evaluated in future prevention trials.

Acceptability and use of a dapivirine vaginal ring in a phase III trial.

BACKGROUND: The MTN-020/ASPIRE trial evaluated the safety and effectiveness of the dapivirine vaginal ring for prevention of HIV-1 infection among African women. A nested qualitative component was conducted at six of 15 study sites in Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and adherence to the ring. METHOD: Qualitative study participants (n = 214) were interviewed with one of three modalities: single in-depth interview, up to three serial interviews or an exit Focus Group Discussion. Using semistructured guides administered in local languages, 280 interviews were audio-recorded, transcribed, translated, coded and analyzed. RESULTS: We identified three key findings: first, despite initial fears about the ring's appearance and potential side effects, participants grew to like it and developed a sense of ownership of the ring once they had used it. Second, uptake and sustained adherence challenges were generally overcome with staff and peer support. Participants developed gradual familiarity with ring use through trial progression, and most reported that it was easy to use and integrate into their lives. Using the ring in ASPIRE was akin to joining a team and contributing to a broader, communal good. Third, the actual or perceived dynamics of participants' male partner relationship(s) were the most consistently described influence (which ranged from positive to negative) on participants' acceptability and use of the ring. CONCLUSION: It is critical that demonstration projects address challenges during the early adoption stages of ring diffusion to help achieve its potential public health impact as an effective, long-acting, female-initiated HIV prevention option addressing women's disproportionate HIV burden.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

Towards Multidisciplinary HIV-Cure Research: Integrating Social Science with Biomedical Research.

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multidisciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV-cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community.

Disclosure of pharmacokinetic drug results to understand nonadherence.

OBJECTIVES: In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. METHODS: We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1-74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. RESULTS: We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants' explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. CONCLUSION: Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

Editorial: Global action to reduce HIV stigma and discrimination.

There is no question that the stigma and discrimination associated with HIV and AIDS can be reduced through intervention. The inclusion of stigma and discrimination reduction as a critical component of achieving an AIDS-free generation in recent UNAIDS, UN and PEPFAR political initiatives is promising. Yet national governments need evidence on effective interventions at the individual, community and societal levels in order to strategically incorporate stigma and discrimination reduction into national AIDS plans. Currently, the heterogeneity of stigma and discrimination reduction approaches and measurement makes it challenging to compare and contrast evaluated interventions. Moving forward, it is critical for the research community to: (1) clearly link intervention activities to the domains of stigma to be shifted; (2) assess the stigma domains in a consistent manner; and (3) link stigma and discrimination reduction with HIV prevention, care and treatment outcomes (e.g., uptake, adherence and retention of ART). These steps would further advance the scientific evidence base of stigma and discrimination reduction and allow for the identification of effective interventions that could be scaled up by national governments.

Integrating behavioral and biomedical research in HIV interventions: challenges and opportunities.

Recent clinical trials have demonstrated overwhelming success of biomedical tools to prevent the spread of HIV infection. However, the complex and somewhat disparate results of some of these trials have highlighted the need for effective integration of biomedical and behavioral sciences in the design and implementation of any future intervention trial. Integrating behavioral and biomedical sciences will require appropriate behavioral theories that can be used in the context of biomedical clinical trials and multidisciplinary teams working together from the earliest stages of trial design through to completion. It is also clear that integration of behavioral science will be necessary to implement prevention at the population level and reverse the HIV epidemic.

Opportunities for HIV combination prevention to reduce racial and ethnic health disparities.

Despite advances in HIV prevention and care, African Americans and Latino Americans remain at much higher risk of acquiring HIV, are more likely to be unaware of their HIV-positive status, are less likely to be linked to and retained in care, and are less likely to have suppressed viral load than are Whites. The first National HIV/AIDS Strategy (NHAS) has reducing these disparities as one of its three goals by encouraging the implementation of combination high-impact HIV intervention strategies. Federal agencies have expanded their collaborations in order to decrease HIV-related disparities through better implementation of data-driven decision making; integration and consolidation of the continuum of HIV care; and the reorganization of relationships among public health agencies, researchers, community-based organizations, and HIV advocates. Combination prevention, the integration of evidence-based and impactful behavioral, biomedical, and structural intervention strategies to reduce HIV incidence, provides the tools to address the HIV epidemic. Unfortunately, health disparities exist at every step along the HIV testing-to-care continuum. This provides an opportunity and a challenge to everyone involved in HIV prevention and care to understand and address health disparities as an integral part of ending the HIV epidemic in the United States. To further reduce health disparities, successful implementation of NHAS and combination prevention strategies will require multidisciplinary teams, including psychologists with diverse cultural backgrounds and experiences, to successfully engage groups at highest risk for HIV and those already infected with HIV. In order to utilize the comprehensive care continuum, psychologists and behavioral scientists have a role to play in reconceptualizing the continuum of care, conducting research to address health disparities, and creating community mobilization strategies.

Advancing novel HIV prevention intervention research with MSM--meeting report.

HIV continues to exact an enormous toll on society and to disproportionately affect gay and bisexual men and other men who have sex with men (MSM). Innovative prevention interventions are needed to reverse this trend. In August 2009, the U.S. National Institute of Mental Health and the Centers for Disease Control and Prevention convened a meeting of scientists, community representatives, advocates, and federal partners to discuss innovative prevention-intervention science. The meeting was structured to maximize discussion of (1) healthy sex interventions, (2) community and structural interventions, (3) integrated biomedical and behavioral interventions, and (4) interventions to improve uptake of HIV testing. Presentations and discussion focused on research gaps in designing risk-reducing and sexual health-promoting interventions for MSM, including interventions to address mental health, substance use, disclosure, and stigma. This article summarizes the meeting proceedings, highlights key points, and outlines future directions.

Challenges in addressing depression in HIV research: assessment, cultural context, and methods.

Depression is one of the most common co-morbidities of HIV infection. It negatively impacts self-care, quality of life, and biomedical outcomes among people living with HIV (PLWH) and may interfere with their ability to benefit from health promotion interventions. State-of-the-science research among PLWH, therefore, must address depression. To guide researchers, we describe the main diagnostic, screening, and symptom-rating measures of depression, offering suggestions for selecting the most appropriate instrument. We also address cultural considerations in the assessment of depression among PLWH, emphasizing the need to consider measurement equivalence and offering strategies for developing measures that are valid cross-culturally. Finally, acknowledging the high prevalence of depression among PLWH, we provide guidance to researchers on incorporating depression into the theoretical framework of their studies and employing procedures that account for participants with depression.

Mental health considerations in secondary HIV prevention.

Despite substantial attention in the past decade to the co-morbidity of mental health problems among people living with HIV/AIDS (PLWHA), these problems remain a significant barrier to maintaining health and secondary prevention. To address these issues, program staff from the Center for Mental Health Research on AIDS at the NIMH convened a meeting on 19th and 20th July 2007 to discuss the intersection of mental health and HIV. The conveners brought together leaders in the fields of mental illness and HIV to discuss current gaps in the research related to the prevention, diagnosis, and treatment of mental disorders among PLWHA, and how attention to mental health can affect a variety of health outcomes. Attendees were asked to discuss key questions that, if addressed through empirical investigation, could move the field toward the aim of reducing or alleviating the burden of mental illness for those living with HIV disease. The purpose of this brief report is to summarize this meeting's proceedings, overview key points of discussion, and outline areas that may be useful to consider for clinical researchers in the field.

Frequency of adolescent self-cutting as a predictor of HIV risk.

OBJECTIVE: A wide range exists in the frequency of adolescent self-cutting behavior; however, the implications of this variability are relatively unexplored. Although evidence suggesting a relationship between self-harm and sexual risk behaviors has been identified, little is known regarding the relationship between frequency of self-cutting and sexual risk. The present study aimed to test the hypothesis that adolescents who repeatedly self-cut would report more HIV risk behaviors and riskier attitudes than those who had engaged in infrequent self-injury. METHOD: Adolescents (11-18 years; mean age, 15 years) from intensive psychiatric treatment programs with a history of self-cutting (N = 105, 53% female) completed measures of self-cutting, sexual risk behaviors, and risk attitudes. RESULTS: Frequent self-cutting (more than three times, lifetime) was associated with being sexually active, using condoms inconsistently, and sharing cutting instruments. Frequent self-cutters were significantly more likely to be female and nonwhite, and report low self-restraint. They also showed a trend toward being more likely to have a history of sexual abuse. CONCLUSIONS: This study found important differences in self-cutters based on frequency of cutting. Adolescent self-cutting may be a spectrum of behavior that ranges from habitual, repeated behavior contrasted with infrequent, experimental, socially motivated cutting. The associations between frequent cutting, sexual risk, and low self-restraint suggest that common underlying mechanisms may determine these patterns.

Measurement of coping and stress responses in women with breast cancer.

The development of the Responses to Stress Questionnaire-cancer version (RSQ-CV) to assess coping with and responses to the stress of breast cancer is described. The RSQ-CV was completed by 232 women with breast cancer near the time of their diagnosis. Confirmatory factor analyses verified a model that includes three voluntary coping factors (primary control engagement coping, secondary control engagement coping, disengagement coping) and two involuntary stress response factors (involuntary engagement, involuntary disengagement). Internal consistency reliability, and stability over 12 weeks for the five factors were adequate to excellent. Convergent and discriminant validity was examined through correlations with measures of intrusive thoughts, avoidance, and dimensions of perceived control. Significant correlations with symptoms of anxiety and depression are also reported. Applications of the RSQ-CV for research with breast cancer patients are discussed.