Randomized controlled trial to investigate impact of site-based safer sex programmes in Kingston, Jamaica: trial design, methods and baseline findings

Objective To describe the design, methods and baseline findings of a multi‐level prevention intervention to increase consistent condom use among persons at public social sites in Kingston, Jamaica, who have new or concurrent sexual partnerships. Methods A two‐arm randomized controlled trial (RCT) of 147 sites where persons meet new sex partners. Sites were identified by community informants as places where people meet new sexual partners, which include bars, street locations, bus stops, malls and others. Sites were sorted into 50 clusters based on geographic proximity and type of site and randomized to receive a multi‐level site‐based intervention or not. Intervention components include on‐site HIV testing, condom promotion and peer education. Effectiveness of the intervention will be measured by comparing the proportion of persons with new or multiple partners in the past year who report recent inconsistent condom use at intervention vs. control sites. Results Baseline surveys were conducted at 66 intervention (711 men, 845 women) and 65 control sites (654 men, 738 women). Characteristics of intervention and control sites as well as the characteristics of patrons at these sites were similar. The outcome variable was balanced with approximately 30% of men and 25% of women at intervention and control sites reporting a new partner or more than one partner in the past year and recent inconsistent condom use. Conclusions The baseline findings confirm that the population is an appropriate target group for HIV prevention and that randomization will provide the means to estimate programme effectiveness.     

A cluster randomized-controlled trial to determine the effectiveness of Stepping Stones in preventing HIV infections and promoting safer sexual behaviour amongst youth in the rural Eastern Cape, South Africa: trial design, methods and baseline findings

OBJECTIVE: To describe the study design, methods and baseline findings of a behavioural intervention trial aimed at reducing HIV incidence. METHOD: A cluster randomized-controlled trial (RCT) conducted in 70 villages in rural South Africa. A behavioural intervention, Stepping Stones, was implemented in 35 communities in two workshops of 20 men and 20 women in each community who met for 17 sessions (50 h) over a period of 3-12 weeks. Individuals in the control arm communities attended a single session of about 3 h on HIV and safer sex. Impact assessment was conducted through two questionnaire and serological surveys at 12-month intervals. The primary outcome was HIV incidence and secondary measures included changes in knowledge, attitude and sexual behaviours. Qualitative research was also undertaken with 10 men and 10 women from two sites receiving the intervention (one rural and one urban) and five men and five women from one village in the control arm. They were interviewed individually three times prior to the workshops and then 9-12 months later. RESULTS: A total of 2776 participants (1409 intervention and 1367 control) were enrolled at baseline and had an interview, and HIV sero-status was established. HIV baseline prevalence rates in women were 9.8% in the intervention arm and 12.8% in the control arm. In men the prevalence was 1.7% in the intervention arm and 2.1% in the control arm. Demographic and behavioural characteristics were similar in the two arms. In the intervention groups 59.9% of participants attended more than 75% of the sessions. In the control group 66.3% attended the control session. CONCLUSION: This is the third RCT to be conducted in sub-Saharan Africa evaluating a behavioural intervention using HIV incidence as a primary outcome. It is of particular interest as the intervention in question is used in many developing countries. There is good baseline comparability between the study arms and the process data on the workshops suggested that the interventions were feasible and adequately implemented.     

HIV and STI knowledge,testing, and risk among adult crack users in Mexico city: baseline findings from a feasibility study

Recent research has documented crack cocaine’s increasing spread in Mexico, which is likely to contribute to the rapid transmission of HIV and other sexually transmitted infections (STIs). In Mexico, crack use is increasing most rapidly in vulnerable, hard-to-reach populations, where little is known about risk behaviors. This report aims to present baseline data regarding HIV and STI knowledge and testing prevalence from an innovative projection mapping HIV intervention, in which 3-D illusions, animation, and visual text graphics and sound are projected onto buildings with health messages that were designed to disrupt everyday life and connect with the target population. Fifty-eight men and women who used crack in the past month without receiving drug treatment were recruited and interviewed before the projection mapping intervention took place. Testing instruments included a sociodemographic assessment, drug use and treatment profile, HIV and STI knowledge questionnaires, and a sex and drug risk assessment. The mean scores for respondents on the HIV Knowledge Questionnaire (10.5 out of 18, 58.3%) and STD Knowledge Questionnaire (9.5 out of 27, 35.2%) were both low. Respondents also reported high rates of sexual risk behaviors, with 73% reporting never using a condom and 64% never being tested for HIV. This report provides a portrait of STI and HIV risk among a vulnerable population in Mexico City and the need for urgent interventions to prevent the spread of STIs and HIV. The associated projection mapping intervention will seek to increase HIV and STI knowledge and reduce risk in this hard-to-reach population.     

Using behavioural insights to increase HIV self‐sampling kit returns: a randomized controlled text message trial to improve England's HIV self‐sampling service

Objectives

The aim of the study was to determine whether behaviourally informed short message service (SMS) primer and reminder messages could increase the return rate of HIV self‐sampling kits ordered online.

Methods

The study was a 2 × 2 factorial design randomized control trial. A total of 9585 individuals who ordered a self‐sampling kit from www.freetesting.hiv different SMS combinations: 1) standard reminders sent days 3 and 7 after dispatch (control); 2) primer sent 1 day after dispatch plus standard reminders; 3) behavioural insights (BI) reminders (no primer); or 4) primer plus BI reminders. The analysis was restricted to individuals who received all messages (n = 8999). We used logistic regression to investigate independent effects of the primer and BI reminders and their interaction. We explored the impact of sociodemographic characteristics on kit return as a secondary analysis.

Results

Those who received the primer and BI reminders had a return rate 4% higher than that of those who received the standard messages. We found strong evidence of a positive effect of the BI reminders (odds ratio 1.13; 95% confidence interval 1.04–1.23; P = 0.003) but no evidence for an effect of the primer, or for an interaction between the two interventions. Odds of kit return increased with age, with those aged ≥ 65 years being almost 2.5 times more likely to return the kit than those aged 25–34 years. Men who have sex with men were 1.5–4.5 times more likely to return the kit compared with other sexual behaviour and gender identity groups. Non‐African black clients were 25% less likely to return the kit compared with other ethnicities.

Conclusions

Adding BI to reminder messages was successful in improving return rates at no additional cost.     

Effect of a multicomponent behavioural PMTCT cluster randomised controlled trial on HIV stigma reduction among perinatal HIV positive women in Mpumalanga province,South Africa

Background: We evaluate the impact a multicomponent, behavioural, prevention of mother to child transmission (PMTCT), cluster randomised controlled trial on HIV stigma reduction among perinatal HIV infected women in rural South Africa. Methods: In a cluster randomised controlled trial, twelve community health centres (CHCs) in Mpumalanga Province, South Africa, were randomised; pregnant women living with HIV enrolled received either: A Standard Care (SC) condition plus time-equivalent attention-control on disease prevention (SC; 6 CHCs; n =357), or an Enhanced Intervention (EI) condition of SC PMTCT plus the ‘Protect Your Family’ intervention (EI; 6 CHCs; n =342). HIV-infected pregnant women in the SC attended four antenatal and two postnatal video sessions; those in the EI, four antenatal and two postnatal group PMTCT sessions, including stigma reduction, led by trained lay health workers. Maternal PMTCT, HIV knowledge and HIV related stigma were assessed. The impact of the EI was ascertained on stigma reduction (baseline, 12 months postnatally). A series of logistic regression and latent growth curve models were developed to test the impact of the intervention. Results: In all, 699 women living with HIV were recruited during pregnancy (8–24 weeks), and assessments were completed prenatally at baseline and at 12 months (59.5%) postnatally. Baseline scores of overall HIV related stigma and the four scale factors (personalised stigma, disclosure concerns, negative self-image, and concern public attitudes) decreased at follow-up in the intervention group, while baseline scores of overall stigma and three scale factors (personalised stigma, negative self-image, and concern public attitudes) increased at follow-up in the control group. Using longitudinal analyses, Model 1, which included time-invariant predictors of stigma assessed over the two time periods of baseline and 12 months, increases in stigma from baseline to 12 months were associated with being unemployed, having been diagnosed with HIV before the current pregnancy, and alcohol use. In Model 2, which included time-varying predictors, lower stigma scores were associated with participation in the intervention, greater male partner involvement, and consistent condom use. Conclusion: The enhanced PMTCT intervention, including stigma reduction, administered by trained lay health workers had a significant effect on the reduction of HIV related stigma. Trial registration: clinicaltrials.gov: number NCT02085356     

The Respecting the Circle of Life trial for American Indian adolescents: rationale,design, methods,and baseline characteristics

This paper describes the rationale, design, methods, and baseline results of a randomized controlled trial to evaluate the impact of an adapted evidence-based intervention (EBI), “Respecting the Circle of Life” (RCL) to reduce behavioral risks for HIV/AIDS among American Indian (AI) adolescents. A participatory approach shaped intervention adaptation and study design. A total of 267 participants (aged 13–19) were randomized by peer groups of the same sex to receive the RCL intervention or a control condition. Self-report assessments were administered at four intervals. The sample was predominately female (57%), had low HIV knowledge prevention scores, early sexual initiation (mean 14.6 years), and 56% reported intention to use a condom at next sex. Baseline characteristics were evenly distributed between groups with the exception of age and extrinsic reward scores. This is the first rigorous evaluation of an adapted EBI for HIV/AIDS prevention among AI adolescents, an at-risk and understudied population.     

Septicaemia in a population‐based HIV clinical cohort in rural Uganda, 1996–2007: incidence,aetiology, antimicrobial drug resistance and impact of antiretroviral therapy

Objectives To describe the incidence and aetiology of septicaemia, and antimicrobial drug resistance in HIV‐infected and uninfected individuals, and the impact of antiretroviral therapy (ART) on septicaemia. Methods Between 1996 and 2007, we followed up a rural population–based cohort of HIV‐infected and uninfected participants. The aetiology and incidence of septicaemia, and antimicrobial drug resistances were determined. ART became available in 2004, and its impact on the incidence of septicaemia was examined. Results The overall septicaemia incidence (per 1000 pyrs) was 32.4 (95% CI 26.2–40.6) but was only 2.6 (95% CI 1.3–6.2) in HIV‐negative patients and 67.1 (95% CI 53.4–85.4) in HIV‐positive patients not on ART. Among those on ART, the overall incidence was 71.5 (95% CI 47.1–114.3), although it was 121.4 (95%CI 77.9–200.4) in the first year on ART and 37.4 (95%CI 18.9–85.2) in the subsequent period. Septicaemia incidence was significantly associated with lower CD4 counts. The commonest isolates were Streptococcus pneumoniae (SPN, n = 68) and Non‐typhi salmonellae (NTS, n = 42). Most SPN isolates were susceptible to ceftriaxone and erythromycin, while resistance to cotrimoxazole and penicillin was common. All NTS isolates were susceptible to ciprofloxacin, but resistance to cotrimoxazole and chloramphenicol was common. Conclusions Septicaemia incidence was higher in HIV‐infected than in HIV‐uninfected participants, and it remained high for some time among those who started ART. Starting ART earlier at higher CD4 counts is likely to lead to lower septicaemia incidence. Both SPN and NTS, the commonest isolates, were resistant to most commonly available antimicrobials. Blood culture laboratory surveillance systems to monitor antibiotic susceptibility and inform treatment guidelines are needed in Africa.     

The Regai Dzive Shiri Project: a cluster randomised controlled trial to determine the effectiveness of a multi-component community-based HIV prevention intervention for rural youth in Zimbabwe--study design and baseline results

Objective To assess the effectiveness of a community‐based HIV prevention intervention for adolescents in terms of its impact on (1) HIV and Herpes simplex virus type 2 (HSV‐2) incidence and on rates of unintended pregnancy and (2) reported sexual behaviour, knowledge and attitudes. Methods Cluster randomised trial of a multi‐component HIV prevention intervention for adolescents based in rural Zimbabwe. Thirty communities were selected and randomised in 2003 to early or deferred intervention implementation. A baseline bio‐behavioural survey was conducted among 6791 secondary school pupils (86% of eligibles) prior to intervention implementation. Results Baseline prevalences were 0.8% (95% CI: 0.6–1.0) for HIV and 0.2% (95% CI: 0.1–0.3%) for HSV‐2. Four girls (0.12%) were pregnant. There was excellent balance between study arms. Orphans who made up 35% of the cohort were at increased risk of HIV [age–sex adjusted odds ratio 3.4 (95% CI: 1.7–6.5)]. 11.9% of young men and 2.9% of young women reported that they were sexually active (P < 0.001); however, there were inconsistencies in the sexual behaviour data. Girls were less likely to know about reproductive health issues than boys (P < 0.001) and were less likely to have used and to be able to access condoms (P < 0.001). Conclusion This is one of the first rigorous evaluations of a community‐based HIV prevention intervention for young people in southern Africa. The low rates of HIV suggest that the intervention was started before this population became sexually active. Inconsistency and under‐reporting of sexual behaviour re‐emphasise the importance of using externally validated measures of sexual risk reduction in behavioural intervention studies.     

Endothelial progenitor cells in relation to endothelin-1 and endothelin receptor blockade: A randomized,controlled trial

Aims

Endothelial progenitor cells (EPC) represent an endogenous repair mechanism involving rendothelialization and neoangiogenesis. Patients with both diabetes and vascular disease have low numbers of circulating EPC. The endothelium-derived peptide, endothelin-1 (ET-1), is increased in patients with type 2 diabetes and vascular complications and has been suggested to contribute to endothelial dysfunction. Therefore, we investigated the relation between EPC and plasma ET-1 and the effect of dual ET-1 receptor antagonist treatment.

Methods

In this double blind study patients with type 2 diabetes mellitus and microalbuminuria were randomized to treatment with the dual ETA/ETB receptor antagonist bosentan treatment (125 mg bid; n = 17) or placebo (n = 19) for four weeks. Different EPC subpopulations were enumerated by flow cytometry using triple staining (CD34, CD133, KDR) at baseline at the end of treatment. Viability was assessed by 7AAD and Annexin-V-staining.

Results

Baseline ET-1 levels correlated significantly with C-reactive protein levels. Patients with ET-1 levels above the median value had higher levels of CD34⁺CD133⁺ and CD34⁺KDR⁺ EPC. There was no difference in CD34⁺ and CD34⁺CD133⁺KDR⁺ cells, markers of EPC apoptosis or circulating markers of endothelial damage between patients with ET-1 levels below or above the median. Four week treatment with bosentan did not change EPC levels.

Conclusion

Among patients with type 2 diabetes and vascular disease, high plasma levels of ET-1 are associated with higher number of EPC. The recruitment of EPC does not seem to be regulated via ET-1 receptor activation since treatment with a dual ET-1 receptor blocker did not affect circulating EPC numbers.     

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double‐blind,randomized, controlled,acute feeding,equivalence trial

Aim

To assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes.

Methods

A double‐blind, multiple‐crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by > 1‐week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75‐g glucose solution. A standard 75‐g oral glucose tolerance test protocol was followed with blood samples at ?30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC).

Results

Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [C_max], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre‐specified equivalence margins of ±20%.

Conclusion

Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long‐term randomized trials to confirm the sustainability of these improvements.     

The DATAS rationale and design: a controlled, randomized trial to assess the clinical benefit of dual chamber (DDED) defibrillator.

Single chamber (SC) implantable cardioverter defibrillators (ICDs) have several limitations that might be relevant during follow-up, like atrial pacing requirements, inadequate therapies, sustained atrial tachyarrhythmias and difficulties to achieve an accurate diagnosis of the arrhythmia. Dual chamber (DC) ICDs offer an attractive and rational solution, although controversy remains if the costs and complexity of these devices offer a real clinical advantage. The Dual Chamber & Atrial Tachyarrhythmias Adverse Events Study (DATAS) was designed to analyze the ability of DC ICD, DDED, to reduce clinically significant adverse events compared with SC ICD in a non-selected population with conventional indications for ICD implantation. This is a prospective, multicentre, randomized, open labelled study, with three arms: two of them (simulated SC ICD and true DC ICD) cross-over, and the third (true SC ICD) parallels the other two. The composite primary end point comprises four Clinically Significant Adverse Events (CSAE): (1) all-cause mortality, (2) invasive intervention, hospitalization or prolongation of hospitalization due to cardiovascular cause, (3) inappropriate shocks, and (4) sustained symptomatic atrial tachyarrhythmias that (a) require urgent termination or (b) last more than 48h leading to therapeutic intervention. Secondary end points constitute each of the individual components of CSAE, cardiovascular status, quality of life and a detailed analysis of atrial and ventricular arrhythmias. To date (June 2003) there have been 343 patients enroled from 947 screened patients. The projected enrollment includes 360 patients and the conclusion of the study is expected at the beginning of 2005.     

A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain

Aims Because smoking cessation rates might be improved by combining drugs and by reducing post‐cessation weight gain, we tested the smoking cessation efficacy, safety and effect on body weight of adding the nicotine patch to rimonabant, a cannabanoid type‐1 receptor antagonist that reduces body weight. Design Randomized double‐blind placebo‐controlled trial. Setting Fifteen US research centers. Participants A total of 755 smokers (≥15 cigarettes/day). Intervention Rimonabant (20 mg daily) was given open‐label for 9 weeks. The 735 participants completing week 1 were randomized at day 8 (target quit day) to add a nicotine patch (n = 369) or placebo patch (n = 366) for 10 weeks (21 mg daily for 8 weeks plus a 2‐week taper). Participants received weekly smoking counseling and were followed for 24 weeks. Measurements Biochemically validated 4‐week continuous abstinence at end‐of‐treatment (weeks 6–9; primary end‐point); 7‐day point prevalence abstinence at weeks 9 and 24; sustained abstinence (weeks 6–24); change in body weight; and adverse events. Findings Rimonabant plus nicotine patch was superior to rimonabant plus placebo in validated continuous abstinence at weeks 6–9 (39.0% versus 21.3%; odds ratio 2.36, 95% confidence interval: 1.71–2.37; P < 0.01) and in all other efficacy measures. Mean end‐of‐treatment weight gain among quitters did not differ between groups (0.04 kg for combination versus 0.49 kg for rimonabant only, P = 0.15) and was similar in weight‐concerned smokers. Serious adverse event rates did not differ between groups. Depression‐ and anxiety‐related adverse events occurred in 32 (4.2%) and 44 (5.8%) subjects, respectively; eight (1.1%) and nine (1.2%) subjects stopped the drug due to depression and anxiety, respectively. Conclusions Adding a nicotine patch to rimonabant was well tolerated and increased smoking cessation rates over rimonabant alone. There was little post‐cessation weight gain in either group, even among weight‐concerned smokers, during drug treatment.     

A randomized, placebo-controlled trial of monthly azithromycin prophylaxis to prevent sexually transmitted infections and HIV-1 in Kenyan sex workers: study design and baseline findings

Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections (STIs) and HIV-1 in a cohort of Nairobi female sex workers (FSWs). A questionnaire was administered and a medical examination was performed. HIV-negative women were randomly assigned to either one gram azithromycin or placebo monthly. Mean age of the 318 women was 32 years, mean duration of sex work 7 years and mean number of clients was 4 per day. High-risk behaviour was frequent: 14% practised anal intercourse, 23% sex during menses, and 3% used intravenous drugs. While 20% reported condom use with all clients, 37% never use condoms. However, STI prevalence was relatively low: HIV-1 27%, bacterial vaginosis 46%, Trichomonas vaginalis 13%, Neisseria gonorrhoeae 8%, Chlamydia trachomatis 7%, syphilis 6% and cervical intraepithelial neoplasia (CIN) 3%. It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes, including a proposed trial of HIV prevention through STI chemoprophylaxis.