These recommendations may be updated when more data become available regarding the incidence and risk factors of DTG resistance with more widespread use in routine clinical practice. Figure 4 shows the outline of the virological monitoring of patients on DTG-based first-line ART and the recommended response to results. Open in a separate window FIGURE 4 Virological monitoring of patients receiving dolutegravir-based first-line antiretroviral therapy and response to results. 13. stopping antiretroviral therapy DrugCdrug interactions Tuberculosis Pregnancy and breastfeeding Liver disease Renal disease Psychiatric disease Methylprednisolone hemisuccinate Malaria Antiretroviral drug-induced liver injury Dyslipidaemia Immune reconstitution inflammatory syndrome Opportunistic infection prophylaxis Adherence Acknowledgments Abbreviations References What is new in the 2020 guidelines update? Key updates ? A recommendation for dolutegravir (DTG)-based therapies as the preferred first-line antiretroviral therapy (ART) option (section 11).? Updated guidelines for second- and third-line ART regimens (section 13).? New recommendations on the management of patients on DTG-based therapies who have an elevated viral load (section 12).? A lowering of the threshold for virological failure from 1000 copies/mL to 50 copies/mL (section 8).? A recommendation against routine cluster of differentiation 4 (CD4+) monitoring in patients who are clinically well once the CD4+ count is 200 cells/L (section 9).? Updated recommendations for isoniazid preventive therapy (IPT) in human immunodeficiency virus (HIV)-positive patients (section 27).? A recommendation for the use of low-dose prednisone as prophylaxis for paradoxical tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) in TB/HIV co-infected patients commencing ART within 1 month of TB therapy (section 26). 1. Preamble Key principles 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. Dolutegravir-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 according to their low- and middle-income status. Hence, only the treatment and diagnostic options that are available in southern Africa are included. Methylprednisolone hemisuccinate 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 and as a result of inhibition of the hepatic enzyme Uridine 5′-diphospho-glucuronosyltransferase. Although the hyperbilirubinaemia is harmless and does not reflect a drug-induced liver injury (DILI), a minority of patients will become visibly jaundiced, and this may require changing ART regimens for cosmetic reasons. ? Common pitfall: Mistaking the unconjugated hyperbilirubinaemia sometimes seen with ATV use with a DILI. Conversely, it is equally important to note that ARVs can also cause a true DILI, and therefore a complete liver function test (LFT) panel should be performed to distinguish between the two possibilities. Darunavir Darunavir has the highest barrier to resistance of any PI: Mutations selected by ATV or LPV can compromise DRV efficiency. For patients with mutations that confer any degree of resistance to DRV (e.g. I50V, L76V and I84V), the dose should be DRV/r 600 mg/100 mg twice daily. For patients without any DRV mutations, the drug can be taken at a dose of DRV/r 800 mg/100 mg once daily. There KIAA0700 is evidence, however, that DRV/r 400 mg/100 mg once daily may be sufficient in this scenario, especially for patients with suppressed VLs at the time of the switch.33,34 Compared Methylprednisolone hemisuccinate with a twice-daily dosing, a once-daily dosing offers the benefits of reduced pill burden and better side effect profile. As with ATV, DRV cannot be co-prescribed with RIF-based TB treatment. ? Common pitfall: Prescribing ATV or DRV in patients receiving RIF-based TB treatment. Lopinavir/ritonavir is the only PI combination that can be co-prescribed safely with RIF, but the dose of LPV/r must be adjusted as above. 6. Initiation and timing of antiretroviral therapy Key points ? All individuals diagnosed with HIV should be initiated on ART.? Delays to start ART should be minimised. Several studies have demonstrated that it is safe to initiate.? ART on.