Lobomycosis Epidemiology and Management: The Quest for a Cure for the Most Neglected of Neglected Tropical Diseases.

Lobomycosis is a chronic disease caused by Lacazia loboi, which is endemic to the Amazon rainforest, where it affects forest dwellers in Brazil. There is no disease control program and no official therapeutic protocol. This situation contributes to an unknown disease prevalence and unmet needs of people disabled by this disease who seek access to treatment. This review provides an update on the subject with an emphasis on therapeutic advances in humans. All relevant studies that addressed epidemiology, diagnosis, or therapeutics of lobomycosis were considered. Seventy-one articles published between 1931 and 2021 were included for a narrative literature review on the epidemiology and quest for a cure. An effective therapy for lobomycosis has been found following decades of research led by the State Dermatology Program of Acre in the Amazon rainforest, where the largest number of cases occur. This discovery opened new avenues for future studies. The main recommendations here, addressed to the Brazilian Ministry of Health, are for lobomycosis to become a reportable disease to ensure that disease prevalence is measured, and that it be prioritized such that affected individuals may access treatment free-of-charge.

An Approach to Reducing Problematic Data in an ACASI Sexual Behavior Assessment.

Minimizing error in self-reported sexual behavior could reduce investigators' likelihood of rejecting truly successful interventions to decrease HIV and STI transmission risk. Sexual behavior assessments can elicit problematic data. This may manifest in the form of elevated levels of non-response, inaccurate point estimates, or misclassification errors resulting in inappropriately answering or, perhaps more importantly, skipping questions. We programed conversational interviewing elements into 20 sexual behavior questions in an exit survey of gay bathhouse patrons (N = 459) administered using ACASI. Those elements, called alternate pathways, included follow-up questions to responses to confirm that operational definitions were applied in the answer (with return to the initial question if confirmation failed), and assurances of confidentiality and requests for best guesses in reaction to non-response (including "don't know"). These elements were invoked in nearly 10% of participants, and approximately 74% of all invocations resulted in a usable numeric response, or 87% if the data need only estimate prevalence. Almost two-thirds of the problematic data issues occurred in answers to sexual contact questions, with others related to follow-up questions about specific sexual behavior. It is at this level of important filtering questions where the benefits of the approach are likely to be maximized.

Integrating Phylogenetic Biomarker Data and Qualitative Approaches: An example of HIV Transmission Clusters as a Sampling Frame for Semistructured Interviews and Implications for the COVID-19 Era.

Mixed methods studies of human disease that combine surveillance, biomarker, and qualitative data can help elucidate what drives epidemiological trends. Viral genetic data are rarely coupled with other types of data due to legal and ethical concerns about patient privacy. We developed a novel approach to integrate phylogenetic and qualitative methods in order to better target HIV prevention efforts. The overall aim of our mixed methods study was to characterize HIV transmission clusters. We combined surveillance data with HIV genomic data to identify cases whose viruses share enough similarities to suggest a recent common source of infection or participation in linked transmission chains. Cases were recruited through a multi-phase process to obtain consent for recruitment to semi-structured interviews. Through linkage of viral genetic sequences with epidemiological data, we identified individuals in large transmission clusters, which then served as a sampling frame for the interviews. In this article, we describe the multi-phase process and the limitations and challenges encountered. Our approach contributes to the mixed methods research field by demonstrating that phylogenetic analysis and surveillance data can be harnessed to generate a sampling frame for subsequent qualitative data collection, using an explanatory sequential design. The process we developed also respected protections of patient confidentiality. The novel method we devised may offer an opportunity to implement a sampling frame that allows for the recruitment and interview of individuals in high-transmission clusters to better understand what contributes to spread of other infectious diseases, including COVID-19.

Randomized controlled trial of a positive affect intervention to reduce HIV viral load among sexual minority men who use methamphetamine.

INTRODUCTION: In the era of HIV treatment as prevention (TasP), evidence-based interventions that optimize viral suppression among people who use stimulants such as methamphetamine are needed to improve health outcomes and reduce onward transmission risk. We tested the efficacy of positive affect intervention delivered during community-based contingency management (CM) for reducing viral load in sexual minority men living with HIV who use methamphetamine. METHODS: Conducted in San Francisco, this Phase II randomized controlled trial tested the efficacy of a positive affect intervention for boosting and extending the effectiveness of community-based CM for stimulant abstinence to achieve more durable reductions in HIV viral load. From 2013 to 2017, 110 sexual minority men living with HIV who had biologically confirmed, recent methamphetamine use were randomized to receive a positive affect intervention (n = 55) or attention-control condition (n = 55). All individual positive affect intervention and attention-control sessions were delivered during three months of community-based CM where participants received financial incentives for stimulant abstinence. The 5-session positive affect intervention was designed to provide skills for managing stimulant withdrawal symptoms as well as sensitize individuals to natural sources of reward. The attention-control condition consisted of neutral writing exercises and self-report measures. RESULTS: Men randomized to the positive affect intervention displayed significantly lower log10 HIV viral load at six, twelve and fifteen months compared to those in the attention-control condition. Men in the positive affect intervention also had significantly lower risk of at least one unsuppressed HIV RNA (≥200 copies/mL) over the 15-month follow-up. There were concurrent, statistically significant intervention-related increases in positive affect as well as decreases in the self-reported frequency of stimulant use at six and twelve months. CONCLUSIONS: Delivering a positive affect intervention during community-based CM with sexual minority men who use methamphetamine achieved durable and clinically meaningful reductions in HIV viral load that were paralleled by increases in positive affect and decreases in stimulant use. Further clinical research is needed to determine the effectiveness of integrative, behavioural interventions for optimizing the clinical and public health benefits of TasP in sexual minority men who use stimulants such as methamphetamine.

Randomized controlled trial of a positive affect intervention for methamphetamine users.

BACKGROUND: Contingency management (CM) is an evidence-based intervention providing rewards in exchange for biomarkers that confirm abstinence from stimulants such as methamphetamine. We tested the efficacy of a positive affect intervention designed to boost the effectiveness of CM with HIV-positive, methamphetamine-using sexual minority men. METHODS: This attention-matched, randomized controlled trial of a positive affect intervention delivered during CM was registered on www.clinicaltrials.gov (NCT01926184). In total, 110 HIV-positive sexual minority men with biologically confirmed, recent methamphetamine use were enrolled. Five individual sessions of a positive affect intervention (n = 55) or an attention-control condition (n = 55) were delivered during three months of CM. Secondary outcomes examined over the 3-month intervention period included: 1) psychological processes relevant to affect regulation (i.e., positive affect, negative affect, and mindfulness); 2) methamphetamine craving; 3) self-reported stimulant use (past 3 months); and 4) cumulative number of urine samples that were non-reactive for stimulants (i.e., methamphetamine and cocaine) during CM. RESULTS: Those randomized to the positive affect intervention reported significant increases in positive affect during individual sessions and increases in mindfulness over the 3-month intervention period. Intervention-related improvements in these psychological processes relevant to affect regulation were paralleled by concurrent decreases in methamphetamine craving and self-reported stimulant use over the 3-month intervention period. CONCLUSIONS: Delivering a positive affect intervention may improve affect regulation as well as reduce methamphetamine craving and stimulant use during CM with HIV-positive, methamphetamine-using sexual minority men.

"Knowing Your Status and Knowing Your Partner's Status Is Really Where It Starts": A Qualitative Exploration of the Process by Which a Sexual Partner's HIV Status Can Influence Sexual Decision Making.

Gay and bisexual men are at disproportionate risk for human immunodeficiency virus (HIV) infection. While prevention efforts often emphasize consistent condom use, there is growing evidence that men are using seroadaptive safer-sex strategies, such as serosorting and seropositioning. This qualitative analysis of 204 HIV-negative and HIV-positive gay and bisexual men explored the ways that a sexual partner's HIV status can influence safer-sex strategies and sexual decisions. The majority of the respondents reported that they were influenced by their partners' HIV status. Those respondents who reported no influence discussed adhering to safer-sex rules that were not dependent on partner status and a lack of concern about HIV. Conversely, respondents who reported influence identified three primary areas of influence: psychological impacts, partner preference and selection, and specific behavioral intentions and strategies. A conceptual model explicating a potential process by which respondents use partner serostatus information in shaping sexual decisions is presented.

A community-engaged randomized controlled trial of an integrative intervention with HIV-positive, methamphetamine-using men who have sex with men.

BACKGROUND: Contingency management (CM) is an evidence-based intervention providing tangible rewards as positive reinforcement for abstinence from stimulants such as methamphetamine. Integrative approaches targeting affect regulation could boost the effectiveness of CM in community-based settings and optimize HIV/AIDS prevention efforts. METHODS/DESIGN: This randomized controlled trial with HIV-positive, methamphetamine-using men who have sex with men (MSM) is examining the efficacy of a 5-session, individually delivered positive affect regulation intervention - Affect Regulation Treatment to Enhance Methamphetamine Intervention Success (ARTEMIS). ARTEMIS is designed to sensitize individuals to non-drug-related sources of reward as well as assist with managing depression and other symptoms of stimulant withdrawal during CM. HIV-positive, methamphetamine-using MSM who are enrolled in a community-based, 12-week CM program are randomized to receive ARTEMIS or an attention-matched control condition. Follow-up assessments are conducted at 3, 6, 12, and 15 months after enrollment in CM. Four peripheral venous blood samples are collected over the 15-month follow-up with specimen banking for planned biomarker sub-studies. The primary outcome is mean HIV viral load. Secondary outcomes include: sustained HIV viral suppression, T-helper cell count, psychological adjustment, stimulant use, and potentially amplified transmission risk behavior. DISCUSSION: Implementation of this randomized controlled trial highlights the importance of delineating boundaries between research activities and community-based service provision. It also provides insights into best practices for integrating the distinct agendas of academic and community partners in clinical research. This trial is currently enrolling and data collection is anticipated to be completed in September of 2018. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov ( NCT01926184 ) on August 16, 2013.

Bathhouse distribution of HIV self-testing kits reaches diverse, high-risk population.

We distributed free OraQuick In-home HIV Test® kits to men at a gay bathhouse. Men were systematically selected to receive a coupon, which could be redeemed that night for an HIV self-testing kit. Those offered the coupon were asked to take an 11-item survey. About 181 men received coupons, of whom 92 (51%) accepted the coupon, and 61 (66%) men redeemed the coupon. Those who redeemed test kits and completed a survey (n = 53) were more ethnically diverse (χ(2) = 100.69, p < .01) than those receiving the coupon. More than half had not tested in the past 6 months (50%) or never tested (7%). Importantly, men who had never tested or who last tested more than 6 months ago were among those most likely to take the free test kit. We found bathhouse distribution could reach a population of men who have sex with men most in need of improved access to HIV testing. Future studies should consider means of improved follow-up and linkage to care for those who test positive.

The Psychological Context of Sexual Compulsivity Among Men Who Have Sex with Men.

Among men who have sex with men (MSM), sexual compulsivity is associated with overlapping psychosocial and behavioral health problems. Because difficulties with emotion regulation are thought to be one important feature, this study examined whether affective states and traumatic stress symptoms were independently associated with key dimensions of sexual compulsivity. Data were collected in San Francisco for the Urban Men's Health Study-2002 from May 24, 2002 to January 19, 2003. In total, 711 MSM recruited via probability-based sampling completed a mail-in questionnaire that assessed psychological factors and substance use. Dissociation related to traumatic stress and any stimulant use in the past 6 months were independently associated with more frequent sexual thoughts or urges. Increased anger and HIV-positive serostatus were independently associated with a greater perception that sexual behavior is difficult to control. Clinical research is needed to examine if interventions targeting emotion regulation and traumatic stress can boost the effectiveness of HIV prevention efforts among MSM who experience difficulties related to managing sexual behaviors.

Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity.

Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-ß and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-ß1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-ß1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-ß1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis.

Use of multiple sex venues and prevalence of HIV risk behavior: identifying high-risk men who have sex with men.

The National HIV/AIDS Strategy emphasizes the importance of bringing prevention to the most at risk populations. Interventions targeting all men who have sex with men (MSM) fail in that respect because only a minority engages in behavior that is likely to lead to HIV infection. Previous studies have shown that MSM who seek male sexual partners in more than one venue type (e.g., bathhouse, cruising area, online) are most likely to engage in unprotected anal intercourse (UAI), compared to men who only meet partners in any one of these setting types or who do not use venues. The present study reports differences in prevalence of UAI among MSM by their use of venue sites to meet sexual partners. A probability sample of 459 bathhouse patrons completed exit surveys. In the 3 months before the current bathhouse visit, 63.5 % visited a bathhouse (not including the visit at which they were recruited), 46.7 % visited a cruising area, 46.5 % used online cruise sites to find sex partners, and 30.9 % reported UAI. While UAI was associated with online cruise site use, prevalence of UAI with men met online was relatively low. The odds of UAI among men who used all three venues were significantly higher compared to men using zero [odds ratio (OR) = 4.4; 95 % confidence interval (CI) 1.6, 12.1)] one (OR = 5.3; 95 % CI 2.2, 12.8) or two venues (OR = 4.3; 95 % CI 1.9, 9.6). The findings suggest that prevention would benefit from screening for venue use to help identify men with the greatest behavioral risk.

Analysis of immune response markers in Jorge Lobo's disease lesions suggests the occurrence of mixed T Helper responses with the dominance of regulatory T cell activity

Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-ß and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-ß1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-ß1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-ß1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis.

Presence of an HIV Testing Program Lowers the Prevalence of Unprotected Insertive Anal Intercourse inside a Gay Bathhouse among HIV-negative and HIV-unknown Patrons.

This study sought to determine whether the presence of HIV testing inside a gay bathhouse reduced sexual risk behavior among patrons. A two-stage, time probability, cluster sample design recruited men exiting a northern California bathhouse in the last 5 weeks of 2001 (N=440), when no HIV testing was offered inside the bathhouse, and again in the last 5 weeks of 2002 (N=412) when HIV testing was offered 5 days a week. Separate logistic regression analyses compared a 2002 HIV testing exposure subgroup to both a 2001 non-exposure subgroup and a 2002 non-exposure subgroup for differences in sexual risk behavior during the bathhouse visit. Prevalence of unprotected insertive anal intercourse was significantly lower in the 2002 exposure subgroup than in the 2002 non-exposure subgroup. Similar results obtained when HIV-positive respondents were excluded. These results indicate on-site HIV testing has a preventive effect on some sexual risk behavior inside the bathhouse.

Community-based harm reduction substance abuse treatment with methamphetamine-using men who have sex with men.

Harm reduction approaches endeavor to assist individuals with avoiding the most detrimental consequences of risk taking behaviors, but limited research has documented the outcomes of harm reduction substance abuse treatment. In total, 211 methamphetamine-using men who have sex with men (MSM) enrolled in two outcome studies of substance abuse treatment programs that were implementing an evidence-based, cognitive-behavioral intervention (i.e., the Matrix Model) from a harm reduction perspective. Study 1 (N = 123) examined changes in self-reported substance use, Addiction Severity Index (ASI) composite scores, and HIV care indicators over a 12-month follow-up. Study 2 (N = 88) assessed changes in substance use, sexual risk taking, and HIV care indicators over a 6-month follow-up. Participants in study 1 reported reductions in cocaine/crack use as well as decreases in the ASI drug and employment composite scores. Among HIV-positive participants in study 1 (n = 75), 47 % initiated or consistently utilized anti-retroviral therapy and this was paralleled by significant increases in self-reported undetectable HIV viral load. Study 2 participants reported reductions in methamphetamine use, erectile dysfunction medication use in combination with other substances, and sexual risk-taking behavior while using methamphetamine. Participants in both studies reported concurrent increases in marijuana use. Taken together, these studies are among the first to observe that clients may reduce stimulant use and concomitant sexual risk-taking behavior during harm reduction substance abuse treatment. Randomized controlled trials are needed to examine the differential effectiveness of harm reduction and abstinence-based approaches to substance abuse treatment.

Gay bathhouse HIV prevention: the use of staff monitoring of patron sexual behavior.

Many HIV prevention interventions have been launched in gay bathhouses and sex clubs since the onset of the AIDS epidemic, such as condom distribution and HIV testing. Perhaps none of these are as intrusive to the venue's environment as what is called "monitoring," which involves staff, during every shift, repeatedly walking throughout the public areas of a bathhouse to check on patrons' sexual behavior. Yet, monitoring has received little evaluation. Between 2002 and 2004, we conducted qualitative interviews with venue managers, staff and patrons in New York City, Los Angeles, and the San Francisco Bay Area. An analysis found that monitoring was influenced by the kinds of space available for sex, suggesting three approaches to monitoring: 1) monitoring all sex in clubs that only had public areas where men had sex ; 2) monitoring some sex in clubs with private rooms for sex; and 3) no monitoring of sex, regardless of the kinds of space for sex. This paper explores each approach as described by club managers, staff, and patrons to understand the potential effectiveness of monitoring as an HIV prevention intervention.

Substance use and HIV risk behavior among men who have sex with men: the role of sexual compulsivity.

The relationship between substance use, sexual compulsivity and sexual risk behavior was assessed with a probability-based sample of men who have sex with men (MSM). Stimulant, poppers, erectile dysfunction medication (EDM), alcohol use, and sexual compulsivity were independently associated with higher odds of engaging in any serodiscordant unprotected anal intercourse (SDUAI). The association of sexual compulsivity with SDUAI was moderated by poppers and EDM use. Behavioral interventions are needed to optimize biomedical prevention of HIV among substance using MSM.

Positive affect and processes of recovery among treatment-seeking methamphetamine users.

BACKGROUND: Revised Stress and Coping Theory proposes that positive affect serves adaptive functions, independent of negative affect. However, scant research has examined whether, how, and under what circumstances positive affect is associated with decreased substance use. METHODS: Eighty-eight methamphetamine-using men who have sex with men (MSM) completed the baseline assessment for substance abuse treatment outcome study which included measures of positive and negative affect, cognitive-behavioral change processes (i.e., approach-oriented coping, self-efficacy for managing methamphetamine triggers, and abstinence-related action tendencies), abstinence-specific social support, and self-reported substance use. Participants also provided a urine sample for toxicology screening. RESULTS: After controlling for demographic characteristics and negative affect, higher positive affect was independently associated with greater approach-oriented coping, abstinence-related action tendencies, and abstinence-specific social support. Positive affect was also independently associated with greater self-efficacy for managing methamphetamine triggers, but only at lower levels of negative affect. Through these cognitive-behavioral and social pathways, positive affect was indirectly associated with lower frequency of stimulant use in the past 30 days, lower odds of reporting stimulant use two or more days in a row, and lower odds of providing a urine sample that was reactive for stimulant metabolites. On the other hand, negative affect was not indirectly associated with any measure of stimulant use. CONCLUSIONS: Clinical research is needed to examine the pathways whereby positive affect may predict better substance abuse treatment outcomes.

Psychological processes and stimulant use among men who have sex with men.

BACKGROUND: Prior research established that psychological factors are associated with the frequency of stimulant (i.e., cocaine, crack, and methamphetamine) use among substance-using men who have sex with men (MSM). The present investigation examined whether and how psychological factors are associated with engagement in any stimulant use in the broader population of MSM. METHODS: A probability sample of 879 MSM residing in San Francisco was obtained using random digit dialing from May of 2002 through January of 2003. Of these, 711 participants (81%) completed a mail-in questionnaire that assessed psychological factors and substance use. After accounting for demographic factors, a multiple logistic regression analysis examined correlates of any self-reported stimulant use during the past 6 months. Path analyses examined if the use of alcohol or other substances to avoid negative mood states (i.e., substance use coping) mediated the associations of sexual compulsivity and depressed mood with stimulant use. RESULTS: Younger age (adjusted OR [AOR]=0.58; 95% CI=0.47-0.70), HIV-positive serostatus (AOR=2.55; 95% CI=1.61-4.04), greater depressed mood (AOR=1.26; 95% CI=1.05-1.52) and higher sexual compulsivity (AOR=1.46; 95% CI=1.18-1.80) were independently associated with increased odds of stimulant use. Substance use coping partially mediated the associations of sexual compulsivity (ß(indirect)=0.11, p<.001) and depressed mood (ß(indirect)=0.13, p<.001) with stimulant use. CONCLUSIONS: Clinical research is needed to examine if interventions targeting sexual compulsivity and emotion regulation reduce stimulant use among MSM.