Rachel Beanland

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%; &tgr;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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.