Although many antiretroviral therapy (ART) guidelines are available internationally, the current guidelines have been written to address issues relevant to southern Africa. A major spur for the current guidelines is the introduction of dolutegravir (DTG) into first- and second-line ART regimens. DTG-based ART regimens hold much promise, although the transition inevitably challenges existing paradigms and generates additional complexities. These guidelines aim to address many of these and to update the text in general to reflect the latest evidence.
As with previous iterations, these guidelines take affordability into account, as countries in the region vary between low- and middle-income countries. Hence, only the treatment and diagnostic options that are available in southern Africa are included. In addition, these guidelines recognise the need to bridge the gap in treatment recommendations between public and private sector programmes, considering that many patients transition between the two sectors for treatment. The format of this iteration of the guidelines has been modified to highlight each sections’ key points and common pitfalls.
- Provide maximal and durable suppression of viral load
- Restore and/or preserve immune function
- Reduce HIV-related infectious and non-infectious morbidity
- Prolong life expectancy and improve quality of life
- Prevent onward transmission of HIV
- Minimise adverse effects of the treatment.
These goals are achieved by suppressing viral replication completely for as long as possible, using well-tolerated and sustainable treatment taken with good adherence. With prolonged viral suppression, the CD4+ lymphocyte count usually increases, which is accompanied by a restoration of pathogen-specific immune function. For most patients, this results in a dramatic reduction in the risk of HIV-associated morbidity and mortality. In patients who start ART with preserved CD4+ counts, ART is able to prevent the decline in CD4+ count observed in untreated patients and prevent clinical complications of HIV infection. It is still unclear whether immune function ever returns to full normality, though long-term cohorts show that patients who adhere well to ART have a near-normal life expectancy.1 Patient adherence to their ART regimen remains a key focus and challenge.
ART should not be stopped unless there is an extremely compelling reason to do so. In most cases where drug toxicities develop, switching the culprit drug(s) should be attempted instead. If non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy is stopped, then we generally do not recommend ‘covering the tail’ with an additional 5–7 days of nucleoside reverse transcriptase inhibitors (NRTIs). There is little evidence for this in patients on long-term ART, and the intracellular half-life of drugs such as tenofovir disoproxil fumarate (TDF) in any case approximates that of the NNRTIs.2 It is important to ensure that the viral load (VL) is suppressed before substituting a single drug for toxicity, otherwise resistance may develop to the new drug, consequently compromising future regimens. However, single-drug substitutions can be done in the first few months of ART without measuring the VL, as the VL may take up to 6 months to become suppressed.
We strongly advise against lamivudine (3TC) monotherapy ‘holding regimens’ in patients who have virological failure. Such regimens can be associated with a rapid fall in CD4+ count. The objective when prescribing ART should always be to provide a regimen that is most likely to achieve virological suppression.