Description of the condition

At the end of 2016, there were approximately 36.7 million people living with HIV worldwide, most of them in low‐ and middle‐income countries (LMICs) (WHO 2017b). Although HIV infection continues to be a leading global cause of death and disability, mortality from the virus has almost halved in the past decade due to the rapid expansion of antiretroviral therapy (ART) (UNAIDS 2016).

The latest guidelines of the World Health Organization (WHO) recognize that people living with HIV/AIDS (PLWH) need to receive a continuum (or cascade) of care in order to fully benefit from ART (WHO 2016), and highlight the importance of all elements of HIV care, including HIV diagnosis, engagement in HIV care, provision of ART, and achievement of viral suppression (Gardner 2011; MacCarthy 2015; Okeke 2014). For this reason, the Joint United Nations Programme on HIV/AIDS (UNAIDS) introduced, in 2014, the 90‐90‐90 goals, which aim to diagnose 90% of all people infected with the virus, reach 90% of ART uptake in those diagnosed with HIV, and achieve a 90% rate of viral suppression among those receiving ART by 2020 (UNAIDS 2014).

Substantial international efforts will be needed to achieve these targets, as only 53% of PLWH were receiving ART in 2016 (UNAIDS 2016). One of the main challenges is attrition in HIV services during the period of linkage from HIV diagnosis to initiating ART (Govindasamy 2014; Losina 2010; Rosen 2011). Disengagement from care while PLWH are being prepared to initiate ART is particularly relevant in sub‐Saharan Africa, where it is estimated that only 57% of those diagnosed with HIV are linked to care (Kranzer 2012). Many affected individuals who disengage from services during this period return only when they have deteriorated clinically and immunologically; this results in higher morbidity and mortality when they do start ART (Fairall 2008; Grinsztejn 2014; HMC 2015). One of the contributing factors to poor engagement in care identified in the literature is the delay in starting ART (Clouse 2013). A longitudinal study in Ethiopia conducted between 2005 and 2013 estimated that 52% of PLWH waited over a month to start ART once they were classified as eligible according to the CD4 criteria and national guidelines (Teklu 2017). Other studies carried out in sub‐Saharan African countries have found similar results (Bassett 2010; Lawn 2006; Reddy 2016). The reasons why ART initiation is frequently delayed are complex and involve structural, social, and psychological factors (Hoehn 2017; Wachira 2014). For example, lack of appropriate healthcare infrastructures or constrains involved in attending the several clinic visits that are often required before ART is offered (Govindasamy 2012).

The WHO now recommends universal ART, irrespective of CD4 cell count and clinical stage (WHO 2016). Asymptomatic PLWH with higher CD4 cell counts have been shown to adhere poorly to ART (Adakun 2013), therefore retention in care and ART adherence are critically important.

One proposed intervention for improving linkage and retention of PLWH in HIV care is rapid ART initiation (starting the therapy as soon as possible after ART eligibility, normally within seven days of HIV diagnosis) (Chan 2016; Pilcher 2017). PLWH considered eligible for ART are normally required to attend HIV services several times for counselling and medical evaluation before starting treatment. It is argued that expediting ART could potentially lead to earlier viral suppression in the medium‐ and long‐term through improved uptake and adherence to ART (Hoenigl 2016; Pilcher 2017; Wilkinson 2015).

There remains, however, uncertainty about the acceptability of rapid ART initiation and its effects on morbidity and long‐term treatment outcomes (Mbonye 2016). Some concerns include: poor ART adherence with rapid ART initiation, since PLWH may not receive sufficient or adequate adherence counselling/education, or both; pill burden due to other concurrent comorbidities or conditions requiring urgent treatment (for example, tuberculosis) (Nachega 2014); and immune reconstitution inflammatory syndrome (IRIS), especially in individuals with advanced disease (CD4 counts < 200 cells/mm³) (Uthman 2015). Rapid ART initiation could be particularly relevant for PLWH with advanced disease, as they are at higher risk of mortality and morbidity (Hakim 2017). However, this cohort of individuals are also at higher risk of IRIS and, therefore, rapid ART should be considered in the context of differentiated care, in which they receive a comprehensive package of care that includes, among other factors, screening for opportunistic infections (for example, cryptococcus antigen), co‐trimoxazole prophylaxis, and more intensive adherence and follow‐up support (Mfinanga 2015; WHO 2016). It is also important to acknowledge that some of these individuals may not be eligible for rapid ART initiation if they are found to have signs and symptoms of opportunistic infections (for example, tuberculosis or cryptococcal meningitis). In these cases, ART initiation should be delayed according to the most current guidelines (WHO 2017a).

In order to evaluate the uptake, efficacy, and safety of rapid ART initiation compared with delayed ART initiation it is essential to consolidate findings from randomized controlled trials (RCTs) evaluating this intervention.

Description of the intervention

The current standard of care post‐HIV diagnosis varies across areas and settings according to the local context (MacCarthy 2015). Countries often include in their national guidelines structural and individual interventions aimed to improve linkage. These include: integration of services, point‐of‐care CD4 cell count, post‐test counselling, peer support, support with HIV disclosure, and addressing any psychosocial barriers identified (NASCOP 2016; NCASC 2009; NDOHSA 2015; Wynberg 2014). Pre‐ART care includes a comprehensive baseline assessment that often involves a clinical and a psychosocial assessment (MoH 2016). These may include several steps such as: physical examination, laboratory tests, opportunistic infection screening, nutritional status assessment, counselling, health insurance evaluation, and education sessions (NDOHSA 2015; Pilcher 2017). These interventions are often carried out over several visits to HIV services, which means that ART initiation is often delayed for several weeks after PLWH are considered eligible for ART (Lawn 2006; Teklu 2017).

High rates of disengagement from care have been reported during this period (Rosen 2011). In order to expedite this process and minimize losses to follow‐up, more rapid ART initiation has been proposed.

For the purposes of this Cochrane Review, we define rapid ART as offering the therapy within seven days after the PLWH is considered eligible for therapy. According to current guidelines, PLWH are considered eligible for ART on the same day as diagnosis unless they are found to have signs or symptoms of opportunistic infections such as tuberculosis or cryptococcal meningitis. With rapid ART, PLWH may receive usual care, but some of the interventions that form part of pre‐ART care are delivered on the same day or within a few days of HIV diagnosis. These include, among others, screening for tuberculosis, physical examination, and an initial counselling and education session (Labhardt 2016; Pilcher 2017; Rosen 2016).

How the intervention might work

Expediting the initiation of ART could improve engagement in care by simplifying and reducing the number of visits a PLWH has to make to HIV services. Delaying ART has been identified in the literature as major contributor to disengagement, particularly in LMICs (Govindasamy 2014).

The HIV continuum of care is a complex process in which every step is influenced by multiple factors, as illustrated in our conceptual model (see Figure 1). This figure shows how the feasibility of rapid ART initiation depends on various health system and provider factors, such as staffing levels, skills, infrastructure, and equipment, which vary across settings (Attawell 2003).

Figure 1

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Conceptual model of factors influencing the HIV care continuum. Abbreviations: PLWH: people living with HIV, ART: antiretroviral therapy, IRIS: immune reconstitution inflammatory syndrome

Uptake of ART is also influenced by various factors (Bolsewicz 2015). Rapid ART could improve uptake of the therapy by reducing the number of PLWH lost to follow‐up in the period of linkage from HIV diagnosis to ART commencement (Pilcher 2017; Rosen 2016). However, as Figure 1 shows, uptake of ART is also influenced by social, economic, and cultural factors, such the family context, as well as individual factors, such as acceptance of the result or the desire for a second opinion. There is lack of consensus on the impact that offering rapid ART may have on these individual factors (Black 2013; Black 2014; Katirayi 2016).

By increasing the number of PLWH starting treatment, rapid ART could increase the absolute number of people retained in care and adhering to treatment. However, initiating rapid ART in PLWH before all baseline screening test results (for opportunistic infections and renal function) are available could result in a higher lost to follow‐up (LTFU) rate (Abay 2015; Chan 2016; Pilcher 2017). This could also result in a higher frequency of regimen modification in those being offered rapid ART initiation (Pilcher 2017).

Finally, rapid ART could also increase the number of PLWH achieving viral suppression through rising numbers of PLWH receiving ART, being engaged in care, and adhering to treatment (Pilcher 2017; Rosen 2016). As ART is started earlier, viral suppression could be achieved faster in those receiving rapid ART, having a positive impact on HIV transmission and HIV‐related morbidity and mortality (Eshleman 2017; Lesko 2016).

Why it is important to do this review

With universal ART being recommended and adopted worldwide, interventions aimed to address poor linkage of care are increasingly relevant. One of these proposed interventions is rapid initiation of ART.

Although it has been suggested that rapid ART initiation could improve engagement in care and increase rates of viral suppression (Rosen 2016), there is conflicting evidence regarding the acceptability and appropriateness of this intervention. Although qualitative and observational studies have found greater than 90% acceptance rates among PLWH who were offered rapid ART (Black 2013; Pilcher 2017), several other studies have found that issues, such as denial, shock, difficulty committing to life‐long treatment, or the need to consult with a partner, may, in addition to other known barriers, hamper the uptake or adherence to rapid ART initiation (Black 2014; Katirayi 2016). Most of these studies have focused on pregnant women receiving same‐day ART under Option B+ of the WHO's programme to prevent mother‐to‐child transmission of HIV. This option was introduced by the WHO in 2011 and offers pregnant women lifelong treatment as opposed to previous approaches where ART was offered for a limited time (Table 1) (UNICEF 2012). Although pregnant women constitute a distinct group with unique motivations for taking ART, the barriers identified in this group may be relevant to other settings. Another area of concern is that with expedited ART initiation, laboratory test results for opportunistic infection screening and renal function may not be available at the time of treatment initiation, which may have a negative impact on the incidence of adverse events, including drug side effects, regimen changes, and the incidence of IRIS (Abay 2015; Pilcher 2017).

The WHO now recommends initiation of ART within one week of diagnosis for those who are ready (WHO 2017a). Evidence for the rapid initiation of ART was investigated in 2017 in a systematic review (Ford 2018). Since the publication of this review, however, new studies have been published that address rapid initiation of ART in the context of complex interventions. Given the emergence of this new evidence, a rigorous appraisal of the current literature, including complex interventions and using established Cochrane methods, will help to clarify the role of rapid ART initiation in HIV care. We also aim to describe the complexity of the above‐mentioned interventions, in order to help readers understand the context in which rapid initiation of ART has been evaluated.