Suchergebnisse

RR-TB treatments, testing bedaquiline and injectable kanamycin
Here, Professor Andre Nunn from Medical Research Council Clinical Trials Unit at UCL, explores tuberculosis with a focus on RR-TB treatments (rifampicin-resistant) and their drug combinations. Tuberculosis (TB) is one of the oldest diseases known to man and its management remains a challenge to public health worldwide. According to the most recent World Health Organisation (WHO) report over 10 million persons fell ill with tuberculosis in 2021. It occurs within all the countries of the world but is most prevalent in low and middle income countries. A total of 1.6 million people died from TB world-wide in 2021 making it the 13th leading cause of death and the second leading infectious disease killer after COVID-19.

Tuberculosis drug regimens and their efficacies
Andrew Nunn, Professor of Epidemiology in the Medical Research Council Clinical Trials Unit at UCL conducts two stages of drug treatment for those with tuberculosis called 'STREAM'. In this clinical trial, stage 1 demonstrated that a 9-month regimen was non-inferior to the 20-month regimen that was currently recommended by the World Health Organisation (WHO), and stage 2 investigated two new shortened regimens; one a fully oral 9-month regimen in which bedaquiline is substituted for the injectable tuberculosis drug, kanamycin, and a 6-month regimen in which both bedaquiline and a shortened intensive phase with kanamycin. After assessing the results of patient data from the trials, as well as from observational studies using bedaquiline, pretomanid and linezolid, the World Health Organisation informed key stakeholders in National TB Programmes of detailed recommendations which will be presented later this year in a 2022 update of the WHO consolidated guidelines, to better TB care and treatment.

STUDY QUESTION: Do injectable and oral contraceptives increase the risk of human immunodeficiency virus (HIV) acquisition in women? SUMMARY ANSWER: After adjusting for confounders, evidence of a significantly increased risk of HIV remained for women using injectable depo-medroxyprogesterone (DMPA) (hazard ratio = 1.49, 95% confidence interval (1.06-2.08)) but not for injectable norethisterone-enanthate (Net-En) or oral contraceptive pills (OC). WHAT IS KNOWN ALREADY: An association between the use of some types of hormonal contraception (HC) methods and an increased risk of HIV, possibly through changes in the genital tract environment and alterations in the immune response, has been previously observed, although not consistently. A recent systematic review of these studies has highlighted the need for more definitive evidence. STUDY DESIGN, SIZE, DURATION: A secondary data analysis of the MDP301 phase 3 microbicide trial was conducted to estimate the effects of use of different methods of HC on the risk of HIV acquisition in women. HIV-negative women (n = 8663) with a median age of 28 years were included in the analysis; 382 HIV seroconverted by 52 weeks follow-up; 10% of women-years were lost to follow-up before 52 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: Contraceptive use was reported at each 4-weekly visit. Cox proportional hazards (PH) models were used to estimate the effects of baseline and current use of injectable DMPA, injectable Net-En and OC compared with no HC, on the risk of HIV, adjusting for baseline and time-updated covariates. Causal effects for 52 weeks of HC use compared with no HC were estimated in a weighted Cox model, censoring women at deviation from baseline HC use (or non-use) or pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, 2499 (29%) women were on DMPA, 1180 (14%) on Net-En, and 1410 (16%) on OC; 3574 (40%) not on HC, started HC in follow-up. Adjusted hazard ratios (HR) for baseline HC use, compared with no HC, were 1.38 (95% confidence interval (CI) 1.07-1.78) for DMPA; 1.18 (0.86-1.62) for Net-En and 0.97 (0.68-1.38) for OC. The estimated causal effects of DMPA and Net-En over 52 weeks were: HR = 1.49 (95% CI 1.06-2.08) and HR = 1.31 (95% CI 0.62-1.61), respectively. LIMITATIONS, REASONS FOR CAUTION: A main limitation of the study was that it was a secondary analysis of data from a study that was not designed to investigate this question. Despite our best efforts, we cannot exclude residual confounding to explain the effect of DMPA. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study should be reviewed by the World Health Organization to determine whether current recommendations on the use of DMPA in settings with high HIV prevalence require modification. STUDY FUNDING/COMPETING INTERESTS: MDP is a partnership of African and European academic/government institutions with commercial organizations, which is funded by the UK Government (DFID and MRC), with support from IPM and EDCTP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: None.

BACKGROUND: The collection of accurate data on adherence and sexual behaviour is crucial in microbicide (and other HIV-related) research. In the absence of a "gold standard" the collection of such data relies largely on participant self-reporting. After reviewing available methods, this paper describes a mixed method/triangulation model for generating more accurate data on adherence and sexual behaviour in a multi-centre vaginal microbicide clinical trial. In a companion paper some of the results from this model are presented [1]. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from a random subsample of 725 women (7.7% of the trial population) using structured interviews, coital diaries, in-depth interviews, counting returned gel applicators, focus group discussions, and ethnography. The core of the model was a customised, semi-structured in-depth interview. There were two levels of triangulation: first, discrepancies between data from the questionnaires, diaries, in-depth interviews and applicator returns were identified, discussed with participants and, to a large extent, resolved; second, results from individual participants were related to more general data emerging from the focus group discussions and ethnography. A democratic and equitable collaboration between clinical trialists and qualitative social scientists facilitated the success of the model, as did the preparatory studies preceding the trial. The process revealed some of the underlying assumptions and routinised practices in "clinical trial culture" that are potentially detrimental to the collection of accurate data, as well as some of the shortcomings of large qualitative studies, and pointed to some potential solutions. CONCLUSIONS/SIGNIFICANCE: The integration of qualitative social science and the use of mixed methods and triangulation in clinical trials are feasible, and can reveal (and resolve) inaccuracies in data on adherence and sensitive behaviours, as well as illuminating aspects of "trial culture" that may also affect data accuracy.

AbstractIntroduction: Tuberculosis (TB) remains the most common cause of death among people living with HIV. Integrating HIV and TB services reduces mortality but is sub‐optimally implemented. Quality improvement (QI) methods offer a low‐cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervention on key process indicators for delivering integrated HIV‐TB care in rural South African primary healthcare (PHC) clinics.MethodsSixteen nurse supervisors, (each with a cluster of clinics) overseeing 40 PHC clinics, were randomized 1:1 to the intervention or the standard of care (SOC) groups. The QI intervention comprised three key components: clinical and QI skills training, on‐site mentorship of nurse supervisors and clinic staff, and data quality improvement activities to enhance accuracy and completeness of routine clinic data. The SOC comprised monthly supervision and data feedback meetings. From 01 December 2016 to 31 December 2018, data were collected monthly by a team of study‐appointed data capturers from all study clinics. This study's outcomes were HIV testing services (HTS), TB screening, antiretroviral therapy (ART) initiation, isoniazid preventive therapy (IPT) initiation and viral load (VL) testing.ResultsThe QI group (eight clusters) comprised 244 clinic staff who attended to 13,347 patients during the trial compared to the SOC group (eight clusters) with 217 clinic staff who attended to 8141 patients. QI mentors completed 85% (510/600) of expected QI mentorship visits to QI clinics. HTS was 19% higher [94.5% vs. 79.6%; relative risk (RR)=1.19; 95% CI: 1.02–1.38; p=0.029] and IPT initiation was 66% higher (61.2 vs. 36.8; RR=1.66; 95% CI: 1.02–2.72; p=0·044), in the QI group compared to SOC group. The percentage of patients screened for TB (83.4% vs. 79.3%; RR=1.05; p=0.448), initiated on ART (91.7 vs. 95.5; RR=0.96; p=0.172) and VL testing (72.2% vs. 72.8%; RR=0.99; p=0.879) was similar in both groups.ConclusionsQI improved HIV testing and IPT initiation compared to SOC. TB screening, ART initiation and VL testing remained similar. Incorporating QI methods into routine supervision and support activities may strengthen integrated HIV‐TB service delivery and increase the success of future QI scale‐up activities.