Review
Combination implementation for HIV prevention: moving from clinical trial evidence to population-level effects

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Summary

The promise of combination HIV prevention—the application of multiple HIV prevention interventions to maximise population-level effects—has never been greater. However, to succeed in achieving significant reductions in HIV incidence, an additional concept needs to be considered: combination implementation. Combination implementation for HIV prevention is the pragmatic, localised application of evidence-based strategies to enable high sustained uptake and quality of interventions for prevention of HIV. In this Review, we explore diverse implementation strategies including HIV testing and counselling models, task shifting, linkage to and retention in care, antiretroviral therapy support, behaviour change, demand creation, and structural interventions, and discusses how they could be used to complement HIV prevention efforts such as medical male circumcision and treatment as prevention. HIV prevention and treatment have arrived at a pivotal moment when combination efforts might result in substantial enough population-level effects to reverse the epidemic and drive towards elimination of HIV. Only through careful consideration of how to implement and operationalise HIV prevention interventions will the HIV community be able to move from clinical trial evidence to population-level effects.

Introduction

The term combination HIV prevention has been used to describe the application of many HIV prevention interventions to maximise population-level effects and potentially bring HIV epidemics under control.1, 2 The landmark results of the HIV Prevention Trials Network trial 052 (HPTN 052),3 a randomised controlled trial (RCT) that showed that antiretroviral therapy (ART) reduces HIV transmission to uninfected partners, established treatment as prevention as one of the cornerstones of combination HIV prevention. These findings came after studies of medical male circumcision (MMC), which reduced male HIV acquisition among circumcised men compared with uncircumcised men in three RCTs.4, 5, 6, 7, 8 These data, along with findings from studies that showed the effectiveness of condoms and some behaviour change interventions,9, 10, 11, 12, 13, 14, 15, 16, 17 the potential of pre-exposure prophylaxis for prevention of HIV,18, 19, 20, 21 and modelling studies that suggested the potential for reversal of the HIV epidemic,22, 23, 24, 25 provide the impetus to test the effectiveness of combined HIV prevention strategies.

This growing evidence base has led to the initiation of several large-scale combination HIV prevention programmes and trials.26, 27 However, the success of these efforts will be dependent on the achievement of high sustained uptake as well as the quality of interventions. Although substantial attention has been directed at what should make up the package of prevention interventions for HIV,2, 4, 26 there has been less discussion of how this package could be implemented—ie, what strategies are needed to achieve broad and sustained population coverage.28, 29, 30, 31 To succeed in controlling HIV, we propose an additional concept: combination implementation for HIV prevention.

We define combination implementation for HIV prevention as the pragmatic, localised application of evidence-based strategies to enable high sustained uptake and quality of interventions for prevention of HIV. Combination implementation strategies will be needed to move from trial-based evidence of efficacy to population-level effects.32, 33, 34 In this Review, we explore potential strategies to be incorporated into combination implementation efforts, focusing first on specific prevention and treatment services and concluding with more cross-cutting issues, and we discuss how these strategies could be used to fulfil the potential of combination HIV prevention in low-income and middle-income countries (LMIC).

Section snippets

HIV testing and counselling

HIV testing and counselling, the gateway to learning one's HIV status, is a necessary component of all combination HIV prevention strategies. HIV testing and counselling can include pre-test counselling, risk-behaviour assessment, informed consent, and post-test counselling on the basis of test results to provide individually tailored risk reduction messages. HIV testing and counselling alone can offer HIV prevention benefits through reduction of sexual risk behaviours, particularly among

Task shifting

Task shifting is the rational redistribution of tasks among health workforce teams from higher trained providers to those who need less training.76 It is a direct response to the health worker human resource crisis in LMIC, which is a substantial barrier to implementation of combination HIV prevention.131, 132 Several observational task shifting studies have focused on shifting ART care from physicians to nurses and findings from these studies have typically shown that task shifting can be

Key populations for HIV infection

Key populations for HIV infection include, but are not limited to, sex workers and their clients, men who have sex with men, and injecting drug users.157 The importance of these populations as crucial target groups for HIV prevention efforts is increasingly being recognised.158, 159, 160, 161, 162, 163 Combination HIV prevention efforts need a “know your epidemic” approach, which acknowledges that these often disadvantaged and marginalised populations might be important drivers of local and

Discussion

In this Review, we have sought to broadly consider various evidence-based implementation strategies that could be incorporated in a combination implementation approach to realise the combination HIV prevention goal of reduced HIV incidence. Several strategies were identified, although the evidence base for many is limited. Furthermore, there is a scarcity of evidence on how best to combine different implementation strategies and what the benefits and trade-offs of different combinations might

Search strategy and selection criteria

References for this Review were identified through searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials with the terms “operations research”, “operational research”, “implementation research”, and “implementation science”, limited by “HIV” and “AIDS” terms without language restrictions. We also reviewed bibliographies of pertinent articles and hand searched high-impact journals in the specialty and authors' archives. Included papers were those undertaken in

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