Zambian Peer Educators for HIV Self-Testing (ZEST) study: rationale and design of a cluster randomised trial of HIV self-testing among female sex workers in Zambia

BACKGROUND: HIV testing and knowledge of status are starting points for HIV treatment and prevention interventions. Among female sex workers (FSWs), HIV testing and status knowledge remain far from universal. HIV self-testing (HIVST) is an alternative to existing testing services for FSWs, but little evidence exists how it can be effectively and safely implemented. Here, we describe the rationale and design of a cluster randomised trial designed to inform implementation and scale-up of HIVST programmes for FSWs in Zambia. METHODS: The Zambian Peer Educators for HIV Self-Testing (ZEST) study is a 3-arm cluster randomised trial taking place in 3 towns in Zambia. Participants (N=900) are eligible if they are women who have exchanged sex for money or goods in the previous 1 month, are HIV negative or status unknown, have not tested for HIV in the previous 3 months, and are at least 18 years old. Participants are recruited by peer educators working in their communities. Participants are randomised to 1 of 3 arms: (1) direct distribution (in which they receive an HIVST from the peer educator directly); (2) fixed distribution (in which they receive a coupon with which to collect the HIVST from a drug store or health post) or (3) standard of care (referral to existing HIV testing services only, without any offer of HIVST). Participants are followed at 1 and 4 months following distribution of the first HIVST. The primary end point is HIV testing in the past month measured at the 1-month and 4-month visits. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards at the Harvard T.H. Chan School of Public Health in Boston, USA and ERES Converge in Lusaka, Zambia. The findings of this trial will be presented at local, regional and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: Pre-results; NCT02827240

The Effect of HIV Self-Testing Delivery Models on Female Sex Workers' Sexual Behaviors: A Randomized Controlled Trial in Urban Uganda.

HIV self-testing increases recent and frequent HIV testing among female sex workers (FSWs) in urban Uganda. Using results from a randomized controlled trial, we aim to establish the effect of HIV self-testing delivery models on FSWs’ sexual behaviors in this setting. Clusters of one peer educator and eight participants were 1:1:1 randomized to: (1) direct provision of an HIV self-test, (2) provision of a coupon for facility collection of an HIV self-test, or (3) referral to standard-of-care HIV testing services. Sexual behaviors were self-reported at 1 and 4 months. From October to November 2016, 960 participants were enrolled and randomized. At 4 months, there were no statistically significant differences in participants’ sexual behaviors, including inconsistent condom use, across study arms. We do not find any changes in sexual risk-taking among FSWs in response to the delivery of HIV self-tests. Routine policies for HIV self-testing are likely a behaviorally safe component of comprehensive HIV prevention strategies

HIV risk and pre-exposure prophylaxis interest among female bar workers in Dar es Salaam: cross-sectional survey

OBJECTIVE: Female bar workers (FBW) in East Africa often conduct sex work to supplement their incomes, and may be vulnerable to HIV acquisition. Pre-exposure prophylaxis (PrEP) offers protection against HIV acquisition. However, there is little research on FBW's sexual health. Our objective was to determine HIV risk behaviours and interest in PrEP among FBW in the largest city in East Africa. DESIGN: Cross-sectional survey covering respondents' work and personal lives, including social and behavioural risk factors for HIV. The survey aimed to determine the feasibility of working with FBW and HIV prevalence estimates. Those who did not report being HIV positive were asked about their knowledge of and interest in PrEP. All women were offered free on-site HIV testing and counselling (HTC). SETTING: Eight randomly selected workplaces, that is, bars, in Kinondoni district, Dar es Salaam (DSM). PARTICIPANTS: 66 FBW (≥18 years) selected at random from all women working in selected bars on the day of visit. RESULTS: Half of respondents reported having had sex for money: 20% with bar clients only, 15% with other men only and 15% with both. Almost all (98%) reported ≥1 non-commercial partners in the past 12 months; only 30% reported using condoms with these partners. 85% of respondents had ever been pregnant; 44% had had an unintended pregnancy. Only 5% of respondents had ever heard of PrEP. However, 54% were somewhat/very interested in daily-pill PrEP and 79% were somewhat/very interested in long-acting injectable PrEP. When asked to rank modalities, long-acting injectable PrEP was the most preferred. Seven per cent of the 56 respondents who completed HTC tested HIV positive. CONCLUSIONS: FBW in DSM have elevated risk factors for HIV acquisition, and PrEP appears highly acceptable. Studies developing PrEP delivery models and assessing PrEP initiation and adherence in FBW appear warranted

Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2

The Relevance of Breast Cancer Subtypes in the Outcome of Neoadjuvant Chemotherapy

BACKGROUND: Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy. METHOD: A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Tumors were classified according to their receptor status in estrogen receptor (ER)-positive tumors (HER2-negative), triple-negative tumors, and HER2-positive tumors. The type of surgery feasible prior to neoadjuvant chemotherapy was compared with the actual surgery performed. RESULTS: The overall increase in breast-conserving surgery was 37% (73 of 198). In patients with ductal and lobular carcinomas this increase was 41% (63 of 152, 95% confidence interval [95% CI] 0.34-0.49) and 20% (7 of 35, 95% CI 0.10-0.36), respectively (P = 0.02). Half of the patients with lobular carcinoma had to undergo a secondary mastectomy because of incomplete resection margins. In ER-positive, triple-negative and HER2-positive tumors, the increase in breast-conserving surgery was 39% (42 of 109, 95% CI 0.30-0.48), 24% (11 of 45, 95% CI 0.14-0.38), and 45% (20 of 44, 95% CI 0.32-0.60) (P = 0.11). The pCR rate in ductal and lobular carcinomas was 12% (23 of 195) and 2% (1 of 42), respectively (P = 0.09). In ER-positive, triple-negative and HER2-positive tumors the pCR rates were 2% (3 of 138), 28% (16 of 57), and 18% (10 of 56), respectively. Multivariate analysis showed that the receptor-based subtype was the only significant predictor of pCR (P = 0.004). CONCLUSION: In lobular tumors the benefit with regard to breast-conserving surgery of neoadjuvant chemotherapy is questionable. Although in ER-positive tumors the pCR rate is low, the increase in breast-conserving surgery was remarkable in ductal ER-positive tumor

“But the moment they find out that you are MSM…”: a qualitative investigation of HIV prevention experiences among men who have sex with men (MSM) in Ghana’s health care system

Abstract: The prevalence of HIV in Ghana is 1.3%, compared to 17% among men who have sex with men (MSM). There is limited empirical data on the current health care climate and its impact on HIV prevention services for Ghanaian MSM. The purposes of this study were to investigate (1) MSM’s experiences using HIV prevention resources, (2) what factors, including health care climate factors, influenced MSM’s use of prevention resources and (3) MSM self-identified strategies for improving HIV/sexually transmitted infection (STI) prevention among MSM in Ghanaian communities. Methods: We conducted 22 focus groups (n = 137) with peer social networks of MSM drawn from three geographic communities in Ghana (Accra, Kumasi, Manya Krobo). The data were examined using qualitative content analysis. Interviews with individual health care providers were also conducted to supplement the analysis of focus group findings to provide more nuanced illuminations of the experiences reported by MSM..

Helicobacter pylori infection might be responsible for the interconnection between type 1 diabetes and autoimmune thyroiditis

<p>Abstract</p> <p>Background</p> <p>Higher serological prevalence rates of helicobacter pylori (H. pylori) infection have been reported in patients with type 1 diabetes (T1DM) and autoimmune thyroiditis (AT). Patients with T1DM are at increased risk for developing other autoimmune diseases, most commonly AT. It is unknown whether H. pylori infection could explain the high prevalence of thyroid autoantibodies and AT in T1DM. The aim of the current study was to evaluate anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) autoantibodies in correlation with anti-H. pylori IgG and IgA in young patients with T1DM.</p> <p>Methods</p> <p>Anti-H. Pylori IgG, IgA, anti-TPO and anti-Tg antibodies titers were measured in 162 euthyroid patients with T1DM and 80 healthy controls matched for age, sex and socioeconomic status.</p> <p>Results</p> <p>Seroprevalence of H. pylori was significantly higher in patients with T1DM than in healthy controls; 79% vs. 51.2%, p < 0.001. Anti H. pylori IgG was positive in 61.1% of patients with T1DM and 30% of controls, p < 0.001, anti H. pylori IgA was positive in 74% of patients with T1DM and 32.5% of controls, p < 0.001. Thyroid autoimmunity was also significantly higher in patients with T1DM than in controls; 56.7% vs. 6.2%, p < 0.001. Anti-TPO was positive in 25.3% of patients with T1DM and 3.7% of controls, p < 0.001, anti-Tg was positive in 47.5% of patients with T1DM and 6.2% of controls, p < 0.001. With simple and multiple regression analysis anti-H. pylori IgG and IgA titers were positively and significantly correlated with Anti-TPO and anti-Tg titers in patients with T1DM.</p> <p>Conclusion</p> <p>our results support the idea of a connection between H. pylori infection and the occurrence of anti-TPO, anti-Tg autoantibodies and AT in young patients with T1DM. So, H. pylori infection could be considered as an environmental trigger for development of AT in T1DM. Young patients with T1DM should be screened for H. pylori infection.</p