Treatment Outcomes of Treatment-Naïve Hepatitis C Patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts

Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor

Outcomes of clofazimine for the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis

Background Current anti-tuberculosis therapeutics are not sufficiently effective against drug-resistant tuberculosis (DR-TB), and there is a need for new drugs and therapeutic approaches. It has been proposed that repurposing clofazimine for DR-TB treatment might be one way to increase therapeutic options. Methods We conducted a systematic review of studies reporting on the efficacy and safety of clofazimine as part of combination therapy for DR-TB. Six databases and six conference abstract sites were searched from inception until April 2012. All studies involving the use of clofazimine in the treatment of DR-TB were included. Results Twelve studies, comprising 3489 patients across 10 countries, were included in this review. Treatment success ranged from 16.5% (95% CI 2.7%-38.7%) to 87.8% (95% CI 76.8%-95.6%), with an overall pooled proportion of 61.96% achieving treatment success (95% CI 52.79%-71.12%) (τ2 0.07). Mortality, treatment interruptions, defaulting and adverse events were all in line with DR-TB treatment outcomes overall. The most commonly reported adverse events were gastrointestinal disturbances and skin pigmentation. Conclusions The available evidence to date suggests that clofazimine could be considered as an additional therapeutic option in the treatment of DR-TB. The optimal dose of clofazimine and duration of use require further investigatio

Efficacy of HIV Postexposure Prophylaxis: Systematic Review and Meta-analysis of Nonhuman Primate Studies

Background. The efficacy of antiretrovirals as postexposure prophylaxis (PEP) to prevent viral acquisition was demonstrated in nonhuman primate models of human immunodeficiency virus (HIV) in the early 1990s. To complement the evidence base for efficacy of HIV PEP in humans, we systematically reviewed the published data on PEP efficacy across animal studies. Methods. PubMed, Web of Science, and Embase were searched from inception to 31 May 2014 for randomized and nonrandomized studies reporting seroconversions among uninfected animals exposed to HIV or simian immunodeficiency virus, irrespective of route of exposure. Seroconversion risk data were pooled using random-effects models, and associations explored through meta-regression. Results. Twenty-five studies (408 primates) were included for review. The risk of serconversion was 89% lower among animals exposed to PEP compared with those that did not receive PEP (odds ratio, 0.11 [95% confidence interval, .05-.23]). Heterogeneity was low (I2 = 0.0%). In meta-regression, a significant association was found between timing of PEP and seroconversion and the use of tenofovir compared with other drugs. Conclusions. This review provides further evidence of the protective benefit of PEP in preventing HIV acquisition, and the importance of initiating PEP as early as possible following virus exposur

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis.

Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods: We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results: Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). Conclusions: The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL

Choice of Antiretroviral Drugs for Postexposure Prophylaxis for Adults and Adolescents: A Systematic Review

Background. The choice of preferred regimens for human immunodeficiency virus postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data have become available regarding the safety and tolerability of newer antiretroviral drugs. We undertook a systematic review to assess the safety and efficacy of antiretroviral options for PEP to inform the World Health Organization guideline revision process. Methods. Four databases were searched up to 1 June 2014 for studies reporting outcomes associated with specific PEP regimens. Data on PEP completion and discontinuation due to adverse events was extracted and pooled estimates were obtained using random-effects meta-analyses. Results. Fifteen studies (1830 PEP initiations) provided evaluable information on 2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10 studies (1755 initiations) provided evaluable information on the third drug, which was usually a protease inhibitor. The overall quality of the evidence was rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95% confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP discontinuation due to an adverse event was lower among people taking TDF-based PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For the 3-drug comparison, PEP completion rates were highest for the TDF-based regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+ lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%). Conclusions. The findings of this review provide evidence supporting the use of coformulated TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will depend on setting; for resource-limited settings, LPV/r is a reasonable choice, pending the improved availability of better-tolerated drugs with less potential for drug-drug interaction

Patient-reported barriers to adherence to antiretroviral therapy : a systematic review and meta-analysis

Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.; We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children.; Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence

Public health benefits of shifting from hospital-focused to ambulatory TB care in Eastern Europe: Optimising TB investments in Belarus, the Republic of Moldova, and Romania

High rates of drug-resistant tuberculosis (DR-TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR-TB are substantially higher than treating drug-susceptible TB, and higher yet if DR-TB services are delivered in hospital. The WHO recommends that multidrug-resistant (MDR) TB be treated using mainly ambulatory care, shown to have non-inferior health outcomes, however, there has been a delay to transition away from hospital-focused MDR-TB care in certain Eastern European countries. Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania, to minimise a combination of TB incidence, prevalence, and mortality by 2035. A primary focus of these studies was to determine the health benefits and financial savings that could be realised if DR-TB service delivery shifted from hospital-focused to ambulatory care. Here we provide a comprehensive assessment of findings from these studies to demonstrate the collective benefit of transitioning from hospital-focused to ambulatory TB care, and to address common regional considerations. We highlight that transitioning from hospital-focused to ambulatory TB care could reduce treatment costs by 20% in Romania, 24% in Moldova, and by as much as 40% in Belarus or almost 35 million US dollars across these three countries by 2035 without affecting quality of care. Improved TB outcomes could be achieved, however, without additional spending by reinvesting these savings in higher-impact TB diagnosis and more efficacious DR-TB treatment regimens. We found commonalities in the large portion of TB cases treated in hospital across these three regional countries, and similar obstacles to transitioning to ambulatory care. National governments in the Eastern European region should examine barriers delaying adoption of ambulatory DR-TB care and consider lost opportunities caused by delays in switching to more efficient treatment modes

Public health benefits of shifting from inpatient to outpatient TB care in Eastern Europe: optimising TB investments in Belarus, the Republic of Moldova, and Romania

Background: High rates of drug-resistant tuberculosis (DR TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR TB are substantially higher than treating drug-susceptible TB, and higher yet if DR TB services are delivered in hospital. Therefore, countries are encouraged to transition from inpatient to ambulatory-focused TB care, which has been shown to have non-inferior health outcomes. / Methods: Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania to minimise a combination of active TB cases, prevalence of active TB, and TB-related deaths by 2035. These mathematical optimisations were carried out using Optima TB, a dynamical compartmental model of TB transmission. The focus of this study was to project the health and financial gains that could be realised if TB service delivery shifted from hospital to ambulatory-based care. / Findings: These analyses show that transitioning from inpatient to ambulatory TB care could reduce treatment costs by 5%−31% or almost 35 million US dollars across these three countries without affecting the quality of care. Improved TB outcomes could be achieved without additional spending by reinvesting these potential savings in cost-effective prevention and diagnosis interventions. / Conclusions: National governments should examine barriers delaying the adoption of outpatient DR TB care and consider the lost opportunities caused by delays in switching to more efficient and effective treatment modes

What Proportion of Female Sex Workers Practise anal Intercourse and How Frequently? A Systematic Review and Meta-analysis.

HIV is more efficiently acquired during receptive anal intercourse (AI) compared to vaginal intercourse (VI) and may contribute substantially to female sex workers' (FSW) high HIV burden. We aim to determine how common and frequent AI is among FSW globally. We searched PubMed, Embase and PsycINFO for studies reporting the proportion of FSW practising AI (prevalence) and/or the number of AI acts (frequency) worldwide from 01/1980 to 10/2018. We assessed the influence of participant and study characteristics on AI prevalence (e.g. continent, study year and interview method) through sub-group analysis. Of 15,830 identified studies, 131 were included. Nearly all (N = 128) reported AI prevalence and few frequency (N = 13), over various recall periods. Most studies used face-to-face interviews (N = 111). Pooled prevalences varied little by recall period (lifetime: 15.7% 95%CI 12.2-19.3%, N = 30, I2 = 99%; past month: 16.2% 95%CI 10.8-21.6%, N = 18, I2 = 99%). The pooled proportion of FSW reporting < 100% condom use tended to be non-significantly higher during AI compared to during VI (e.g. any unprotected VI: 19.1% 95%CI 1.7-36.4, N = 5 and any unprotected AI: 46.4% 95%CI 9.1-83.6, N = 5 in the past week). Across all study participants, between 2.4 and 15.9% (N = 6) of all intercourse acts (AI and VI) were anal. Neither AI prevalence nor frequency varied substantially by any participant or study characteristics. Although varied, AI among FSW is generally common, inconsistently protected with condoms and practiced sufficiently frequently to contribute substantially to HIV acquisition in this risk group. Interventions to address barriers to condom use are needed