Table 1.

Questions that need to be addressed in the roll-out of dolutegravir in low- and middle-income countries

Safety Is the use of dolutegravir in pregnancy associated with adverse birth outcomes? What is the frequency and impact of immune reconstitution inflammatory syndrome amongst severely immunocompromised patients who are initiated on dolutegravir in LMICs?

Monitoring effectiveness What is the optimal strategy for viral load and HIVDR testing to manage adults with viraemia on dolutegravir-based regimens? For patients with viraemia on dolutegravir, how can adherence support interventions be integrated with viral load monitoring to maximize virological re-suppression?

Drug interactions Will co-administration of dolutegravir and rifampicin in patients with HIV/TB impact on HIV treatment outcomes?

HIV drug resistance At what rate will dolutegravir HIV drug resistance mutations emerge in LMIC public sector programmes, and in which clinical scenarios? How will pretreatment or acquired NRTI drug resistance mutations impact on the efficacy of dolutegravir-based first or second-line regimens?

Implications for second-line ART If resistance to dolutegravir-based first-line occurs in LMICs, what will be the best second-line regimen and what is the optimal timing for regimen switch? For patients failing current NNRTI-based first-line ART, should dolutegravir be used in a second-line regimen?

Cost-effectiveness Will replacing current first- and/or second-line regimens with dolutegravir-based regimens prove cost-effective? How will the roll-out of dolutegravir impact the cost-effectiveness of viral load monitoring and HIV drug resistance testing?

ART – antiretroviral therapy, HIVDR – HIV drug resistance, LMIC – low- and middle-income country, NNRTI – non-nucleoside reverse transcriptase inhibitor, NRTI – nucleoside reverse transcriptase inhibitor