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.

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.

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.