The World Health Organization's Response to Emerging Human Immunodeficiency Virus Drug Resistance and a Call for Global Action.

The global community, including the World Health Organization (WHO), has committed to ending the AIDS epidemic and to ensuring that 90% of people living with human immunodeficiency virus (HIV) are diagnosed, 90% start treatment, and 90% achieve and maintain virological suppression. The emergence of HIV drug resistance (HIVDR) as antiretroviral treatment programs expand could preclude the 90-90-90 targets adopted by the United Nations General Assembly at the High-Level Meeting on Ending AIDS from being achieved. The Global Action Plan on HIVDR is a call for collective action grounded on normative guidance providing a standardized and robust approach to monitoring, preventing, and responding to HIVDR over the next 5 years (2017-2021). WHO is committed to supporting country, global, regional, and national partners to implement and monitor the progress of the Global Action Plan. This article outlines the key components of WHO's strategy to tackle HIVDR and the role the organization takes in leading the global response to HIVDR.

The Role of ARV Associated Adverse Drug Reactions in Influencing Adherence Among HIV-Infected Individuals: A Systematic Review and Qualitative Meta-Synthesis.

Poor adherence remains a major barrier to achieving the clinical and public health benefits of antiretroviral drugs (ARVs). A systematic review and qualitative meta-synthesis was conduct to evaluate how ARV adverse drug reactions may influence ARV adherence. Thirty-nine articles were identified, and 33 reported that ARV adverse drug reactions decreased adherence and six studies found no influence. Visually noticeable adverse drug reactions and psychological adverse reactions were reported as more likely to cause non-adherence compared to other adverse drug reactions. Six studies reported a range of adverse reactions associated with EFV-containing regimens contributing to decreased adherence. Informing HIV-infected individuals about ARV adverse drug reactions prior to initiation, counselling about coping mechanisms, and experiencing the effectiveness of ARVs on wellbeing may improve ARV adherence.

Barriers and Facilitators to Interventions Improving Retention in HIV Care: A Qualitative Evidence Meta-Synthesis.

Retention in HIV care is vital to the HIV care continuum. The current review aimed to synthesize qualitative research to identify facilitators and barriers to HIV retention in care interventions. A qualitative evidence meta-synthesis utilizing thematic analysis. Prospective review registration was made in PROSPERO and review procedures adhered to PRISMA guidelines. Nineteen databases were searched to identify qualitative research conducted with individuals living with HIV and their caregivers. Quality assessment was conducted using CASP and the certainty of the evidence was evaluated using CERQual. A total of 4419 citations were evaluated and 11 were included in the final meta-synthesis. Two studies were from high-income countries, 3 from middle-income countries, and 6 from low-income countries. A total of eight themes were identified as facilitators or barriers for retention in HIV care intervention: (1) Stigma and discrimination, (2) Fear of HIV status disclosure, (3) task shifting to lay health workers, (4) Human resource and institutional challenges, (5) Mobile Health (mHealth), (6) Family and friend support, (7) Intensive case management, and, (8) Relationships with caregivers. The current review suggests that task shifting interventions with lay health workers were feasible and acceptable. mHealth interventions and stigma reduction interventions appear to be promising interventions aimed at improving retention in HIV care. Future studies should focus on improving the evidence base for these interventions. Additional research is needed among women and adolescents who were under-represented in retention interventions.

End Users' Views and Preferences on Prescribing and Taking Postexposure Prophylaxis for Prevention of HIV: Methods to Support World Health Organization Guideline Development.

The 2014 World Health Organization guidelines for human immunodeficiency virus postexposure prophylaxis (PEP) are the first to combine recommendations for all populations and exposures. To inform the development of these guidelines, we gathered views of end users on key aspects of PEP provision. A mixed-methods approach was used to gather views from the populations for whom the guideline will be of relevance. Data gathered from an online survey, focus group discussions, and previously collected data from in-depth interviews with key populations were used to inform the development of recommendations, in particular where there is a paucity of evidence to assess the benefits and harms of an intervention. This was a successful method to gather end users' views and preferences; however, limitations exist in the generalizability and reliability of the evidence. Future guideline development processes should consider methods to include the views of end users to guide the decision-making process.

Formulating the Future Research Agenda for Postexposure Prophylaxis for HIV: Methodological Challenges and Potential Approaches.

BACKGROUND: During a World Health Organization-convened Guideline Development Group meeting, recommendations for postexposure prophylaxis (PEP) for human immunodeficiency virus were made and research gaps identified. METHODS: We used the PEP clinical management pathway and the Grading of Evidence, Assessment, Development and Evaluation (GRADE) system as a framework to formulate future research questions, describe the most feasible study design, and identify potential biases. RESULTS: Three key study design formats were identified to address 12 research questions: (1) survey- and interview-driven research to identify barriers to access to PEP and related clinical care; (2) establishment of a global PEP registry to generate data to inform the choice of an optimal PEP drug regimen, record drug toxicities arising from specific PEP regimens, and track follow-up and linkage to care (including transition from PEP to preexposure prophylaxis); and (3) randomized controlled trials to determine the optimal adherence promotion strategies necessary for successful outcomes following PEP. CONCLUSIONS: Positioning key clinical and programmatic research questions within the GRADE framework facilitates the formulation of an evidence-based research agenda and future revisions of guidelines.

Starter packs versus full prescription of antiretroviral drugs for postexposure prophylaxis: a systematic review.

BACKGROUND: The provision of starter packs for human immunodeficiency virus postexposure prophylaxis (PEP) is practiced in many settings to facilitate rapid initiation by nonexperts and encourage adherence. However, the impact of starter packs on PEP completion rates has not been systematically assessed. We systematically reviewed the evidence on outcomes associated with starter packs for PEP compared to full prescriptions. METHODS: Four databases and 2 conference abstract sites were searched up to December 2013; this search was updated in 1 database in June 2014. PEP completion rates, stratified by prescribing practice, were pooled using random-effects meta-analysis. RESULTS: Fifty-four studies provided data on 11 714 PEP initiations. Thirty-seven studies, including 3 randomized controlled trials (RCTs) and 34 observational cohorts, provided information on starter packs (although none of the RCTs specifically assessed starter packs), and 17 studies, including 2 RCTs and 15 observational cohorts, provided information on full prescriptions. Overall, outcomes were better when participants were offered a full 28-day course of PEP at initial presentation to healthcare, with fewer refusals (11.4% [95% confidence interval {CI}, 5.3%-17.5%] vs 22% [95% CI, 16.7%-28.1%]) and higher completion rates (70% [95% CI, 56.7%-77.3%] vs 53.2% [95% CI, 44.4%-62.2%]). More than a quarter (28% [95% CI, 21.4%-34.5%]) of individuals provided with a PEP starter pack failed to return for their subsequent appointment and therefore defaulted prior to receiving a full course of PEP. The quality of the evidence overall was rated as very low. CONCLUSIONS: The findings of this review suggest that starter packs do not improve adherence to PEP and may result in lower adherence and completion rates.

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 (I(2) = 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 exposure.

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 interactions.

Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China.

BACKGROUND: This paper reports findings from the prevalence survey conducted in Shandong China in 2010, a province with a population of 94 million. This study aimed to estimate TB prevalence of the province in 2010 in comparison with the 2000 survey; and to compare yields of TB cases from different case finding approaches. METHODS: A population based, cross-sectional survey was conducted using multi-stage random cluster sampling. 54,279 adults participated in the survey with a response rate of 96%. Doctors interviewed and classified participants as suspected TB cases if they presented with persistent cough, abnormal chest X-ray (CXRAY), or both. Three sputum specimens of all suspected cases were collected and sent for smear microscopy and culture. RESULTS: Adjusted prevalence rate of bacteriologically confirmed cases was 34 per 100,000 for adults in Shandong in 2010. Compared to the 2000 survey, TB prevalence has declined by 80%. 53% of bacteriologically confirmed cases did not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65's. CONCLUSIONS: The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to identify TB cases without clear symptoms.

Enhancing Public Health HIV Interventions: A Qualitative Meta-Synthesis and Systematic Review of Studies to Improve Linkage to Care, Adherence, and Retention.

Although HIV services are expanding, few have reached the scale necessary to support universal viral suppression of individuals living with HIV. The purpose of this systematic review was to summarize the qualitative evidence evaluating public health HIV interventions to enhance linkage to care, antiretroviral drug (ARV) adherence, and retention in care. We searched 19 databases without language restrictions. The review collated data from three separate qualitative evidence reviews addressing each of the three outcomes along the care continuum. 21,738 citations were identified and 24 studies were included in the evidence review. Among low and middle-income countries in Africa, men living with HIV had decreased engagement in interventions compared to women and this lack of engagement among men also influenced the willingness of their partners to engage in services. Four structural issues (poverty, unstable housing, food insecurity, lack of transportation) mediated the feasibility and acceptability of public health HIV interventions. Individuals living with HIV identified unmet mental health needs that interfered with their ability to access HIV services. Persistent social and cultural factors contribute to disparities in HIV outcomes across the continuum of care, shaping the context of service delivery among important subpopulations.

Factors Influencing Sexual Behaviour Between Tourists and Tourism Employees: A Systematic Review.

BACKGROUND: Increased travel abroad has a significant impact on the incidence and prevalence of Sexually Transmitted Infections (STIs). Previous reviews have focused on the knowledge, attitudes and behaviour of tourists and acquisition of STIs. Less is known about the impact on tourism operators in countries visited by tourists. The aim of this review is to ascertain factors influencing sexual behaviour between workers in the tourism industry and tourists; exploring the prevalence of sexual behaviour between the two populations, their perceptions of sexual risk while engaging in sexual activities and the knowledge of tourism operators regarding STIs. METHODS: A systematic review was conducted. Database searches were performed in Medline/Ovid, EMBASE, Cochrane library and CINAHL for studies published between 2000 and March 2016. Grey literature searches were completed in the NHS database and Google Scholar between 2000 and December 2013. Papers were independently selected by two researchers. Data were extracted and critically appraised using a pre-designed extraction form and adapted CASP checklist. RESULTS: The search identified 1,602 studies and 16 were included after review of the full text. Studies were conducted in nine countries. Findings suggest that STI knowledge, attitude and practice were fairly good among tourists and tourism workers, but there is a need for pre-travel advice for travellers, especially those travelling to low and middle-income countries. Greater importance was given to tourists than to tourism operators and locals interacting with tourists. Studies suggest that as a group both tourist and tourist workers were likely to engage in sexual activities. Overall, both condom use and STI screening were low, among tourists as well as tourism operators. Furthermore, studies reported links between drug and alcohol use and sexual behaviour and risk taking. CONCLUSION: Although less research appeared to have been conducted among tourism workers than tourists, it does demonstrate the need for education, training and promotion of travel medicine. STI screening, pre-travel advice, travel history in terms of contracting STIs and safe-sex awareness-raising are needed. More and better sexual health education and relevant tourism policies are needed globally.

Interventions to improve the rate or timing of initiation of antiretroviral therapy for HIV in sub-Saharan Africa: meta-analyses of effectiveness.

INTRODUCTION: As global policy evolves toward initiating lifelong antiretroviral therapy (ART) regardless of CD4 count, initiating individuals newly diagnosed with HIV on ART as efficiently as possible will become increasingly important. To inform progress, we conducted a systematic review of pre-ART interventions aiming to increase ART initiation in sub-Saharan Africa. METHODS: We searched PubMed, Embase and the ISI Web of Knowledge from 1 January 2008 to 1 March 2015, extended in PubMed to 25 May 2016, for English language publications pertaining to any country in sub-Saharan Africa and reporting on general adult populations. We included studies describing interventions aimed at increasing linkage to HIV care, retention in pre-ART or uptake of ART, which reported ART initiation as an outcome. We synthesized the evidence on causal intervention effects in meta-analysis of studies belonging to distinct intervention categories. RESULTS AND DISCUSSION: We identified 22 studies, which evaluated 25 interventions and included data on 45,393 individual patients. Twelve of twenty-two studies were observational. Rapid/point-of-care (POC) CD4 count technology (seven interventions) (relative risk, RR: 1.26; 95% confidence interval, CI: 1.02-1.55), interventions within home-based testing (two interventions) (RR: 2.00; 95% CI: 1.36-2.92), improved clinic operations (three interventions) (RR: 1.36; 95% CI: 1.25-1.48) and a package of patient-directed services (three interventions) (RR: 1.54; 95% CI: 1.20-1.97) were all associated with increased ART initiation as was HIV/TB service integration (three interventions) (RR: 2.05; 95% CI: 0.59-7.09) but with high imprecision. Provider-initiated testing (three interventions) was associated with reduced ART initiation (RR: 0.91; 95% CI: 0.86-0.97). Counselling and support interventions (two interventions) (RR 1.08; 95% CI: 0.94-1.26) had no impact on ART initiation. Overall, the evidence was graded as low or moderate quality using the GRADE criteria. CONCLUSIONS: The literature on interventions to increase uptake of ART is limited and of mixed quality. POC CD4 count and improving clinic operations show promise. More implementation research and evaluation is needed to identify how best to offer treatment initiation in a manner that is both efficient for service providers and effective for patients without jeopardizing treatment outcomes.

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

OBJECTIVE: To synthesize qualitative evidence on linkage to care interventions for people living with HIV. DESIGN: Systematic literature review. METHODS: We searched 19 databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the Critical Appraisal Skills Programme tool and certainty of evidence was evaluated using the Confidence in the Evidence from Reviews of Qualitative Research approach. RESULTS: Twenty-five studies from 11 countries focused on adults (24 studies), adolescents (eight studies), and pregnant women (four studies). Facilitators included community-level factors (i.e., task shifting, mobile outreach, integrated HIV, and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams), and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions. CONCLUSION: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, integrated HIV, and primary care services. Both community and individual-level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Barriers and facilitators of interventions for improving antiretroviral therapy adherence: a systematic review of global qualitative evidence.

INTRODUCTION: Qualitative research on antiretroviral therapy (ART) adherence interventions can provide a deeper understanding of intervention facilitators and barriers. This systematic review aims to synthesize qualitative evidence of interventions for improving ART adherence and to inform patient-centred policymaking. METHODS: We searched 19 databases to identify studies presenting primary qualitative data on the experiences, attitudes and acceptability of interventions to improve ART adherence among PLHIV and treatment providers. We used thematic synthesis to synthesize qualitative evidence and the CERQual (Confidence in the Evidence from Reviews of Qualitative Research) approach to assess the confidence of review findings. RESULTS: Of 2982 references identified, a total of 31 studies from 17 countries were included. Twelve studies were conducted in high-income countries, 13 in middle-income countries and six in low-income countries. Study populations focused on adults living with HIV (21 studies, n=1025), children living with HIV (two studies, n=46), adolescents living with HIV (four studies, n=70) and pregnant women living with HIV (one study, n=79). Twenty-three studies examined PLHIV perspectives and 13 studies examined healthcare provider perspectives. We identified six themes related to types of interventions, including task shifting, education, mobile phone text messaging, directly observed therapy, medical professional outreach and complex interventions. We also identified five cross-cutting themes, including strengthening social relationships, ensuring confidentiality, empowerment of PLHIV, compensation and integrating religious beliefs into interventions. Our qualitative evidence suggests that strengthening PLHIV social relationships, PLHIV empowerment and developing culturally appropriate interventions may facilitate adherence interventions. Our study indicates that potential barriers are inadequate training and compensation for lay health workers and inadvertent disclosure of serostatus by participating in the intervention. CONCLUSIONS: Our study evaluated adherence interventions based on qualitative data from PLHIV and health providers. The study underlines the importance of incorporating social and cultural factors into the design and implementation of interventions. Further qualitative research is needed to evaluate ART adherence interventions.

Adherence to HIV postexposure prophylaxis: a systematic review and meta-analysis.

INTRODUCTION: We evaluated variations in completion rates for HIV postexposure prophylaxis (PEP) according to the exposure type (occupational, nonoccupational, and sexual assault), patient, and programme characteristics. METHODS: Four major databases were searched together with conference abstract databases from inception to 1 December 2013, updated in PubMed on 1 June 2014. Randomized and nonrandomized studies reporting completion rates for PEP were included regardless of exposure type, age, or geographical location and data pooled using random-effects meta-analysis. RESULTS: Ninety-seven studies, reporting outcomes on 21 462 PEP initiations, were reviewed. Nonoccupational exposure to HIV was the main reason for PEP in 34 studies (n = 11 840), occupational exposure in 22 studies (n = 3058), sexual assault in 26 studies (n = 3093), and the remainder of studies (15 studies, n = 3471) reported outcomes for mixed exposures. Overall, 56.6% [95% confidence (CI) 50.9-62.2%; τ(2) 0.25] of people considered eligible for PEP completed the full standard 28-day course. Compared with the overall estimate of PEP completion, rates were highest for studies reporting PEP for nonoccupational exposures (65.6%, 95% CI 55.6-75.6%) and lowest for sexual assault (40.2%, 95% CI 31.2-49.2%); higher rates of PEP completion were also reported for MSM (67.2%, 95% CI 59.5-74.9%). Completion rates appeared to be lower for adolescents (36.6%, 95% CI 4.0-69.2%) compared with adults (59.1%, 95% CI 53.9-64.2%) or children (64.0%, 95% CI 41.2-86.8%). CONCLUSION: Adherence to a full 28-day course of antiretroviral drugs prescribed for PEP is poor. Efforts should be made to simplify guidelines for prescribers and support adherence for people taking PEP, with particular attention needed for adolescents and victims of sexual assault.