Same-Day Antiretroviral Therapy Initiation for People Living With HIV Who Have Tuberculosis Symptoms

A Systematic Review

Rachael M. Burke; Hannah M. Rickman; Vindi Singh; Thokozani Kalua; Niklaus D. Labhardt; Mina Hosseinipour; Robert J. Wilkinson; Peter MacPherson

Disclosures

HIV Medicine. 2022;23(1):4-15. 

In This Article

Abstract and Introduction

Abstract

Objectives: Tuberculosis symptoms are very common among people living with HIV (PLHIV) initiating antiretroviral therapy (ART), are not specific for tuberculosis disease and may result in delayed ART start. The risks and benefits of same-day ART initiation in PLHIV with tuberculosis symptoms are unknown.

Methods: We systematically reviewed nine databases on 12 March 2020 to identify studies that investigated same-day ART initiation among PLHIV with tuberculosis symptoms and reported both their approach to TB screening and clinical outcomes. We extracted and summarized data about TB screening, numbers of people starting same-day ART and outcomes.

Results: We included four studies. Two studies deferred ART for everyone with any tuberculosis symptoms (one or more of cough, fever, night sweats or weight loss) and substantial numbers of people had deferred ART start (28% and 39% did not start same-day ART). Two studies permitted some people with tuberculosis symptoms to start same-day ART, and fewer people deferred ART (2% and 16% did not start same-day). Two of the four studies were conducted sequentially; proven viral load suppression at 8 months was 31% when everyone with tuberculosis symptoms had ART deferred, and 44% when the algorithm was changed so that some people with tuberculosis symptoms could start same-day ART.

Conclusions: Although tuberculosis symptoms are very common in people starting ART, there is insufficient evidence about whether presence of tuberculosis symptoms should lead to ART start being deferred or not. Research to inform clear guidelines would help to maximise the benefits of same-day ART.

Introduction

People living with HIV (PLHIV) require antiretroviral therapy (ART) as part of comprehensive HIV care services. Antiretroviral therapy should be started as soon as possible after the first positive HIV diagnosis, or after re-engagement in clinical care.[1–3] Tuberculosis (TB) is common in PLHIV and is a particularly important cause of early mortality following HIV diagnosis.[4,5] Screening, treatment and prevention of TB are key interventions for reducing mortality and morbidity for individuals, as well as reducing community TB transmission.

Same-day ART (ART started on the same day as first presentation to HIV services) has been shown to reduce pre-treatment loss to follow-up and was recommended by WHO in their 2017 Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy.[3] That 2017 guideline stated as a 'clinical consideration' that for people with TB symptoms, ART should be 'briefly' delayed whilst investigating for TB – this clinical consideration was amended in March 2021 guidelines to suggest that ART could be started in people with TB symptoms (excluding headache or other neurological symptoms) with 'close follow up within 7 days'.[6] Tuberculosis symptoms are defined as any one of more of fever, cough of any duration, night sweats or weight loss. This rationale to delay ART to investigate for TB is primarily due to concerns of immune reconstitution inflammatory syndrome (IRIS) occurring in people with undiagnosed and untreated TB at the time of ART initiation.[7] However, TB symptoms are very common among PLHIV not yet on ART – 71% prevalence in a systematic review[7] – and are not specific for TB. It can be difficult to either diagnose TB or confidently refute the diagnosis, particularly at a single clinic visit or in a single day. While in theory, sputum testing for TB using nucleic acid amplification tests (NAATs, such as Xpert Mtb/Rif) can be performed in 2 h, in practice NAAT machines are often located off-site and may have testing backlogs; therefore same-day results are usually not available. Furthermore a single negative sputum NAAT does not exclude TB, and some people are unable to produce sputum. If all people with TB symptoms requiring ART initiation had ART initiation deferred, then a large number of people may not be able to access the benefits of same-day ART. Figure 1 summarizes how TB screening to determine same-day ART eligibility might lead to benefits or harms for individuals.

Figure 1.

Schema of how an intervention to screen for tuberculosis (TB) to determine same-day antiretroviral therapy (ART) eligibility might lead to participant harms or benefits. IRIS, immune reconstitution inflammatory syndrome; LTFU, loss to follow-up. Ticks represent possible benefits and crosses possible harms

We undertook a systematic review to synthesize the evidence on the risks and benefits of same-day ART initiation in PLHIV, not already on ART and with TB symptoms. Because there were very few studies that addressed this question directly by describing their TB screening algorithm, we additionally undertook a narrative review of all identified studies of same-day ART initiation, regardless of whether or how TB screening was reported, in order to make recommendations for further research priorities.

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