Applying National Guidelines on ART - Advanced HIV

Authors: Eefje Jong, MD, PhD; Henry Sunpath, MBBS, MFamMed, DipHIVMan, MPH
Editor In Chief: Ian M. Sanne, MBBCH, FCP(SA) (More Info)

Last Reviewed: September 10, 2017 (What's New)

Credit Information

inPractice® Africa’s Continuing Education Unit (CEU) provider, the South African Medical Association, offers physicians 3 CPD points on a 70% pass rate for completing this individual module. Nonphysicians who successfully complete the module will receive a participation certificate. To learn more on CPD credits and participation certificates, click here.

Introduction: Referral and Hospitalisation for HIV-Positive Patients

In South Africa, most HIV-positive patients with no serious concurrent infections who qualify for antiretroviral therapy (ART) can initiate treatment and be subsequently managed close to their homes at a primary care–level facility. However, many patients will require referral either before or once receiving ART.

Several years ago, most patients who needed referral had very low CD4+ cell counts, presented for care with opportunistic infections (OIs), developed OIs and/or immune reconstitution inflammatory syndrome (IRIS) upon initiating ART, experienced severe drug toxicities, or had preexisting comorbidities, such as chronic kidney disease or liver abnormalities that complicated ART management. In the intervening years, however, much has changed across South Africa, with more sites providing free HIV screening and treatment programmes for persons living with HIV (PLHIV). Increasingly, nurse practitioners manage PLHIV who are receiving ART.

In recent years, guidelines regarding when to start ART have evolved rapidly in South Africa and across the world. According to current South African guidelines, all patients in clinical care should be offered testing for HIV infection and all patients with HIV infection should be offered treatment. (Management Guidelines).[ZA NDOH UTT 2016] This universal test and treat (UTT) strategy is similar to that adopted previously by the World Health Organisation (WHO) (Management Guidelines).[WHO ART 2016] In the beginning, early treatment was recommended, but the toxicity related to components of earlier antiretroviral regimens suggested that a more conservative approach was prudent. In addition, in resource-limited areas, ART had to be reserved for the very sickest patients. More recent cohort[Kitahata 2009; Sterne 2009; May 2007] and randomised clinical trial data[INSIGHT 2015; TEMPRANO 2015] have demonstrated significant individual clinical benefit from starting ART immediately in patients with CD4+ cell counts > 500 cells/mm³ rather than deferring until a certain lower CD4+ cell count threshold or clinical indication was met. In fact, a recent meta-analysis of 4 randomised trials of same-day ART vs standard of care demonstrated increased numbers of persons starting ART, increased viral suppression, decreased loss to follow-up, and a trend toward decreased mortality and late return.[Calmy 2017]

Timing of ART has now also become more urgent. The South Africa National Department of Health guideline states that ART should be started as soon as possible and within 2 weeks of the CD4+ cell count being measured. In addition, the initiation of ART should be “fast tracked”—that is, where possible given within 7 days—if the presenting CD4+ cell count is < 200 cells/mm3 or if the individual has advanced HIV-related disease, such as WHO stage IV disease.

On the other hand, new WHO guidelines suggest rapid initiation—that is, same day if possible or within 7 days—for all patients, including those with advanced disease. As recommended previously, ART is delayed for those with tuberculosis (TB) and low CD4+ cell counts and for those with cryptococcal or TB meningitis to avoid induction of IRIS.

Table 1. South Africa National Department of Health: Initiation of ART[ZA NDOH UTT 2016]

Eligible to Start ART

  • All HIV-positive children, adolescents, and adults regardless of CD4+ cell count will be offered ART treatment, prioritising those with CD4+ cell count ≤ 350 cells/mm3
  • Patients in the Pre-ART and Wellness Programme shall be considered for UTT

Timing of ART

  • ART should be started as soon as the patient is ready and preferably within 2 wks of the most recent CD4+ cell count

Special Situations

Immediate ART

  • HIV-positive women who are pregnant or breastfeeding when their HIV-positive status is identified should start ART on the same day as their positive HIV test (unless active TB is present or there is a contraindication to the first-line regimen)

Fast-Track ART (Initiation Within 7 Days of Eligibility)

  • HIV-positive patients with very low CD4+ cell counts (< 200 cells/mm3;)
  • HIV-positive patients with WHO stage IV disease

Patients With TB

  • If patient has TB at HIV diagnosis, start TB treatment first, and then initiate ART as soon as possible and within 8 wks
  • If CD4+ cell count < 50 cells/mm3, initiate ART within 2 wks of starting TB treatment, when the patient’s symptoms are improving and TB treatment is tolerated
  • If CD4+ cell count > 50 cells/mm3, initiate ART within 2-8 wks of starting TB treatment
  • Patients with cryptococcal or TB meningitis should defer ART for 4-6 wks

Nevertheless, many HIV-positive people still present for care with serious conditions that can be difficult to manage effectively at the primary healthcare facility. Many of these people have not yet been tested for HIV, whereas others might have tested positive but disengaged from care (some before and some after initiating ART), only to return to care once they have fallen ill. This indicates that other factors limit patients’ access to HIV testing and medical care.

The healthcare system in the country is very heterogeneous, and model district hospital–supported primary care systems are rare. Consequently, the resources available at referral sites across the country vary widely in ability to accept complex patients, resources available for investigation and treatment, and clinician expertise. Some sites have a formal referral unit, with protocols and guidelines in place to manage complicated cases. In other situations, there may be no dedicated unit for ill PLHIV, but there are skills and expertise to effectively manage patients with complex disease.

In some paradoxical situations, clinicians working in primary care may, in fact, be more skilled in HIV management than clinicians at the referral site. In such cases, the clinicians at the primary care level may need to act cautiously in referring patients and in the longer term, in how they interact with the referral site. Establishing clear lines of communication between the referral site or the hospital treating patients with complex disease and the primary care site is essential, whether the patient is being up-referred or down-referred for long-term follow-up. Some rules of thumb for establishing effective communication between facilities are discussed later in the chapter. These are critical determinants in the decision of if, when, and how to start (or restart) ART at the up-referral site, or whether to wait until patients can be down-referred.

This chapter reviews the clinical presentation and initial diagnostic approach to clinical conditions that South African healthcare workers at district level or in hospital wards are likely to encounter in PLHIV who are not yet receiving ART. The chapter provides guidance regarding which patients should be referred and managed at the district hospitals or other referral centres. Although the chapter does not discuss the treatment of OIs in detail, given the focus of this curriculum on antiretroviral management, it does consider issues such as when, where, and how to start (or restart) ART in complicated patients, including those with serious OIs or comorbidities.

For more information on guideline recommendations for the initiation of ART, please click here.

For more information on first-line ART regimens, please click here.