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Keywords:

  • guidelines;
  • opportunistic infections;
  • antiretroviral therapy

Advances in the treatment of HIV infection with antiretroviral therapy have led to dramatic reductions in opportunistic infections and death. However, late presentation of HIV remains a problem and is a significant contributory cause to death in HIV-seropositive persons in the UK [1]. Furthermore, a recent UK Health Protection Agency (HPA) analysis showed that of 46 700 patients with diagnosed HIV, 19% had CD4 counts <200 cells/μL [2] and therefore remain at significant risk of opportunistic infection.

These guidelines have been drawn up to help physicians investigate and manage HIV-seropositive patients suspected of, or having an opportunistic infection (OI). They are primarily intended to guide practice in the UK and related health systems. Although it is hoped they can provide some guidance in developed countries there are some important distinctions in this environment and individual recommendations may not be as applicable in this setting. The early chapters of these guidelines consider the most common presentations of OI disease such as respiratory, gastrointestinal and neurological disease. These chapters are followed by chapters on specific organisms such as Candida spp, herpes simplex virus and varicella zoster virus, whilst the final chapters discuss special circumstances such as pregnancy, the use of the intensive care unit, the investigation of unwell patients with fever of undetermined origin and management of imported infections.

Each section contains specific information on the background, epidemiology, presentation, treatment and prophylaxis of OIs.

Since the advent of the era of highly active antiretroviral therapy (HAART) the incidence of ‘classic’ opportunistic infections such as Pneumocystis jirovecii and Mycobacterium avium complex has dramatically fallen [3]. The relative contribution of infections that have not formerly been regarded as ‘opportunistic’ has increased. These include community-acquired pneumonia, Clostridium difficile infection and influenza A virus (IAV) infection. The distinction between ‘opportunistic’ and ‘non-opportunistic’ infection is becoming blurred. HIV-seropositive individuals are often less immunocompromised than in the era before HAART. Increasingly it is subtle differences in the susceptibility to, or severity of, infections commonly encountered in immunocompetent individuals that are observed in individuals living with HIV. Recent findings suggest that the strains of pneumococci, a pathogen not regarded as ‘opportunistic’, which are most prevalent in individuals living with HIV behave as ‘opportunistic’ infections [4]. We accept some infections, such as IAV infection, included in these guidelines are not ‘opportunistic’, even using this more relaxed view but believe the current concerns relating to IAV infection and evidence that disease may be more severe in some HIV-seropositive individuals [5] justify their inclusion in these guidelines.

Further information on the role of antiretroviral therapy is also discussed (see below). In the appendices there is an A–Z of drugs used in the management of opportunistic infections. This is intended as a guideline but readers are advised to follow the discussion of dosing and the evidence for specific treatments provided in the text. In some cases alternative treatments are provided in the appendix. These are not discussed in the text and these are mainly of historical interest and readers should be aware that these are not, in general, supported by the evidence base for treatments discussed in the text. It should also be noted that as evidence of drug toxicity, interactions, pregnancy risk and cost is rapidly evolving the table should be considered in association with the updated summary of product characteristics (SPC) for the agent and other relevant sources of drug information.

These guidelines have used the British HIV Association (BHIVA) standard grading for levels of evidence (see Table 1.1).

Table 1.1.   Level of evidence
IaEvidence obtained from meta-analysis of randomized controlled trials
IbEvidence obtained from at least one randomized controlled trial
IIaEvidence obtained from at least one well designed controlled study without randomization
IIbEvidence obtained from at least one other type of well designed quasi-experimental study
IIIEvidence obtained from well designed non-experimental descriptive studies
IVEvidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities

The translation of data into clinical practice is often difficult even with the best possible evidence (i.e. that from two randomized controlled trials) because of trial design, inclusion criteria and precise endpoints. Furthermore, many opportunistic infection treatment studies were performed prior to the availability of HAART. A number of newer diagnostic tests and imaging modalities may help to expedite OI diagnosis and allow earlier initiation of specific therapy with improved outcomes. Recommendations based upon expert opinion have the least evidence but perhaps provide an important reason for writing the guidelines: to produce a consensual opinion about current practice. It must, however, be appreciated that such opinion is not always correct and alternative practices may be equally valid. The recommendations contained in these guidelines should therefore be viewed as guidelines in the true spirit of the term. They are not designed to be restrictive nor should they challenge research into current practice. Similarly, although the BHIVA Opportunistic Infection Guidelines Group seeks to provide guidelines to optimize treatment, such care needs to be individualized and we have not constructed a document that we would wish to see used as a ‘standard’ for litigation.

1.1 Antiretroviral therapy

  1. Top of page
  2. 1.1 Antiretroviral therapy
  3. 1.2 The patient pathway
  4. 1.3 References

The impact of HAART in preventing opportunistic infection is well established. Whilst HAART is the cornerstone of treatment that leads to resolution or improvement in certain OIs, co-prescription of HAART with specific OI treatment is complicated by overlapping toxicities, drug–drug interactions and occasionally a severe immune reconstitution inflammatory syndrome (IRIS), which may complicate the management of both the OI and the underlying HIV infection. Whilst there are limited data with which to provide definitive guidance on when to start HAART in patients with OIs, these guidelines support early initiation of HAART and provide practical information regarding co-prescribing and management of common complications.

1.2 The patient pathway

  1. Top of page
  2. 1.1 Antiretroviral therapy
  3. 1.2 The patient pathway
  4. 1.3 References

The clinical care of patients with known or suspected OIs requires a multidisciplinary approach, drawing on the skills and experience of all healthcare professional groups. Moreover, these guidelines emphasize that inpatients with HIV-related disease often need rapid access to a variety of diagnostic tests and radiological interventions that may not be immediately available at local hospitals. Furthermore, expert interpretation of these tests by supporting specialties such as radiology, histopathology, microbiology and virology is often required. Optimal care of opportunistic infection can only be achieved by the close cooperation of these healthcare professionals and unless all are intimately involved in the care of patients, it is likely that the outcome will be less favourable. In keeping with BHIVA standards for HIV clinical care, patients needing inpatient care for HIV-related disease should ordinarily be admitted to an HIV centre or the relevant tertiary service in liaison with the HIV centre.

1.3 References

  1. Top of page
  2. 1.1 Antiretroviral therapy
  3. 1.2 The patient pathway
  4. 1.3 References