Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

[Needs of pre-exposure prophylaxis for HIV infection and related barriers among men who have sex with men].

Objective: To understand the actual needs for the pre-exposure prophylaxis (PrEP) for HIV infection and the factors hindering PrEP utilization in men who have sex with men (MSM). Methods: Participants were recruited by using MSM social application software Blued 6.5.0 and through MSM peer referral, sample size was 600. An electronic questionnaire survey was conducted anonymously with guidance of investigators via "Questionnaire Star" platform. The contents of the survey included demographic characteristics of the participants, the awareness of PrEP related knowledge, willingness and concerns about using PrEP, actual need for PrEP and self-efficacy of using PrEP. Results: A total of 622 MSM completed the survey, of whom 56.4% (351/622) and 4.3% (27/622) ever heard of and received PrEP, respectively. The need assessment of PrEP showed that 67.2% (418/622) of the participants had actual needs for PrEP and 21.2% (132/622) used PrEP with good self-efficacy. Structural equation modeling analysis showed that the awareness of PrEP related knowledge and concerning about PrEP utilization in MSM played a direct positive role in their self-efficiency of using PrEP, and the effect coefficients were 0.08 and 0.13, respectively. MSM self-discrimination indirectly affected the self-efficiency of using PrEP through concerns about PrEP use, the effect coefficient was 0.035. The result of generalized linear mixed model analysis demonstrated that the utilization of PrEP can improve the self-efficacy of using PrEP (OR=5.55), which increased by 0.14 times and 0.07 times with the increase of 1 score of the awareness of PrEP related knowledge and concern about using PrEP respectively. In addition, this survey found that in the participants, the main concerns about using PrEP were side effects, HIV prevention effect and its expense, accounting for 61.1% (380/622), 60.1% (374/622) and 53.2% (331/622), respectively. Most participants hoped to obtain PrEP services from CDC, MSM social organization and internet, accounting for 75.6% (470/622), 65.4% (407/622), and 63.8% (397/622), respectively. Conclusions: MSM showed difference of high need but low utilization of PrEP services. Low awareness of PrEP related knowledge, concerns about the prevention effect, side effects and expense of PrEP as well as self-discrimination were the factors hindering the use of PrEP in MSM. It is necessary to establish a suitable PrEP service model to meet the needs for PrEP in MSM.

Adjustment to acute or early HIV-1 infection diagnosis to prompt linkage to care and ART initiation: qualitative insights from coastal Kenya.

Diagnosing and treating patients with acute or early HIV-1 infection (AEHI) is an important strategy to prevent HIV-1 transmission. We used qualitative methods to understand factors that facilitate adjustment to AEHI diagnosis, prompt linkage to care and initiation of antiretroviral treatment (ART). Twenty-three AEHI patients (12 women, 11 men) included 18 participants identified at health facilities, and 5 participants identified in a sex worker cohort. Of these, 17 participants (9 women, 8 men) participated in qualitative interviews about their AEHI status 2 weeks after diagnosis. Thirteen participants (7 women, 6 men) returned for a second interview 12 weeks after diagnosis. Interviews explored participants' experiences at the time of and following their diagnosis, and examined perceptions about ART initiation and behavior change recommendations, including disclosure and partner notification. A grounded theory framework was used for analysis, eliciting three important needs that should be addressed for AEHI patients: 1) the need to better understand AEHI and accept one's status; 2) the need to develop healthy strategies and adjust to the reality of AEHI status; and 3) the need to protect self and others through ART initiation, adherence, safer sex, and disclosure. A preliminary conceptual framework to guide further intervention and research with AEHI populations is proposed.

Abstinence-plus programs for HIV infection prevention in high-income countries.

BACKGROUND: Abstinence-plus interventions promote sexual abstinence as the best means of preventing acquisition of HIV, but also encourage safer-sex strategies (eg condom use) for sexually active participants. OBJECTIVES: To assess the effects of abstinence-plus programs for HIV prevention in high-income countries. SEARCH STRATEGY: We searched 30 electronic databases (eg CENTRAL, PubMed, EMBASE, AIDSLINE, PsycINFO) ending February 2007. Cross-referencing, hand-searching, and contacting experts yielded additional citations. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials evaluating abstinence-plus interventions in high-income countries (as defined by the World Bank). Interventions were any efforts that encouraged sexual abstinence as the best means of HIV prevention, but also promoted safer sex. Results were self-reported biological outcomes, behavioral outcomes, and HIV knowledge. DATA COLLECTION AND ANALYSIS: Three reviewers independently appraised 20070 citations and 325 full-text papers for inclusion and methodological quality; 39 evaluations were included. Due to heterogeneity and data unavailability, we presented the results of individual studies instead of a meta-analysis. MAIN RESULTS: Studies enrolled 37724 North American youth; participants were ethnically diverse. Programs took place in schools (10), community facilities (24), both schools and community facilities (2), healthcare facilities (2), and family homes (1). Median final follow-up occurred 12 months after baseline. Results showed no evidence that abstinence-plus programs can affect self-reported sexually transmitted infection (STI) incidence, and limited evidence that programs can reduce self-reported pregnancy incidence. Results for behavioral outcomes were promising; 23 of 39 evaluations found a significantly protective intervention effect for at least one behavioral outcome. Consistently favorable program effects were found for HIV knowledge.No adverse effects were observed. Several evaluations found that one version of an abstinence-plus program was more effective than another, suggesting that more research into intervention mechanisms is warranted. Methodological strengths included large samples and statistical controls for baseline values. Weaknesses included under-utilization of relevant outcomes, self-report bias, and analyses neglecting attrition and clustered randomization. AUTHORS' CONCLUSIONS: Many abstinence-plus programs appear to reduce short-term and long-term HIV risk behavior among youth in high-income countries. Evidence for program effects on biological measures is limited. Evaluations consistently show no adverse program effects for any outcomes, including the incidence and frequency of sexual activity. Trials comparing abstinence-only, abstinence-plus, and safer-sex interventions are needed.

Abstinence-only programs for HIV infection prevention in high-income countries.

BACKGROUND: Abstinence-only interventions promote sexual abstinence as the only means of preventing sexual acquisition of HIV; they do not promote safer-sex strategies (e.g., condom use). Although abstinence-only programs are widespread, there has been no internationally focused review of their effectiveness for HIV prevention in high-income countries. OBJECTIVES: To assess the effects of abstinence-only programs for HIV prevention in high-income countries. SEARCH STRATEGY: We searched 30 electronic databases (e.g., CENTRAL, PubMed, EMBASE, AIDSLINE, PsycINFO) ending February 2007. Cross-referencing, handsearching, and contacting experts yielded additional citations through April 2007. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials evaluating abstinence-only interventions in high-income countries (defined by the World Bank). Interventions were any efforts to encourage sexual abstinence for HIV prevention; programs that also promoted safer-sex strategies were excluded. Results were biological and behavioral outcomes. DATA COLLECTION AND ANALYSIS: Three reviewers independently appraised 20,070 records and 326 full-text papers for inclusion and methodological quality; 13 evaluations were included. Due to heterogeneity and data unavailability, we presented the results of individual studies instead of conducting a meta-analysis. MAIN RESULTS: Studies involved 15,940 United States youth; participants were ethnically diverse. Seven programs were school-based, two were community-based, and one was delivered in family homes. Median final follow-up occurred 17 months after baseline. Results showed no indications that abstinence-only programs can reduce HIV risk as indicated by self-reported biological and behavioral outcomes. Compared to various controls, the evaluated programs consistently did not affect incidence of unprotected vaginal sex, frequency of vaginal sex, number of partners, sexual initiation, or condom use. One study found a significantly protective effect for incidence of recent vaginal sex (n=839), but this was limited to short-term follow-up, countered by measurement error, and offset by six studies with non-significant results (n=2615). One study found significantly harmful effects for STI incidence (n=2711), pregnancy incidence (n=1548), and frequency of vaginal sex (n=338); these effects were also offset by studies with non-significant findings. Methodological strengths included large samples, efforts to improve self-report, and analyses controlling for baseline values. Weaknesses included underutilization of relevant outcomes, underreporting of key data, self-report bias, and analyses neglecting attrition and clustered randomization. AUTHORS' CONCLUSIONS: Evidence does not indicate that abstinence-only interventions effectively decrease or exacerbate HIV risk among participants in high-income countries; trials suggest that the programs are ineffective, but generalizability may be limited to US youth. Should funding continue, additional resources could support rigorous evaluations with behavioral or biological outcomes. More trials comparing abstinence-only and abstinence-plus interventions are needed.

Attempted suicide, psychological health and exposure to harassment among Japanese homosexual, bisexual or other men questioning their sexual orientation recruited via the internet.

OBJECTIVE: To investigate the rates of attempted suicide and its association with psychological distress, experiences of bullying and verbal harassment, and demographic characteristics among Japanese homosexual, bisexual or other men questioning their sexual orientation. DESIGN: A cross-sectional design using Japanese participants recruited through the internet. RESULTS: Of the 1025 respondents, 154 (15%) of the men reported a history of attempted suicide, 716 (70%) showed high levels of anxiety and 133 (13%) showed high levels of depression. 851 (83%) experienced school bullying and 615 (60%) were verbally harassed because of being perceived by others as homosexual. Independent correlates of attempted suicide were psychological distress, history of being verbally harassed, history of sex with a woman, history of meeting a male through the internet, disclosing sexual orientation to six or more friends and not having a university degree. CONCLUSIONS: Mental health services and prevention programmes are needed to deal with the psychological consequences of social stigma for Japanese men who are homosexual, bisexual or questioning their sexual orientation.

Social context of HIV risk behaviours among male-to-female transgenders of colour.

To explore the social context of drug use and sexual behaviours that put male-to-female (MTF) transgenders at risk for HIV, focus groups were conducted consisting of African American, Latina and Asian and Pacific Islander MTF transgenders (N = 48) who reside or work in San Francisco, California. Participants were likely to report having unprotected sex with primary partners to signify love and emotional connection, as well as to receive gender validation from their partners. In contrast, viewing sex work with customers as a business encouraged intentious to use condoms. Safer sex intentions with customers were frequently undermined by urgent financial needs, which stemmed from transphobia, employment discrimination and costly procedures associated with gender transition. Participants reported using drugs as a way to cope with or escape life stresses associated with relationships, sex work, transphobia and financial hardship. Interventions with at-risk MTF transgenders should address the interpersonal and social context of unsafe sex and drug use, particularly the unique roles of relationship issues with male partners, stigma, discrimination and community norms regarding sex work and drug use.