Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research

Journal article

A new first-line antiretroviral therapy (ART) regimen containing dolutegravir is being rolled-out in low-income and middle-income countries (LMICs). Studies from predominantly high-income settings have found that dolutegravir-based regimens have superior efficacy, tolerability and durability compared with existing first-line regimens. However, several questions remain regarding the roll-out of dolutegravir in LMICs, where most people living with HIV are women of reproductive age, TB prevalence can be high, and access to viral load and HIV drug resistance testing is limited. Cohort studies suggest that dolutegravir is safe when initiated in pregnancy, but further data is required to determine the risk of adverse birth outcomes when dolutegravir is initiated pre-conception. Increasing access to viral load testing to monitor the effectiveness of dolutegravir remains crucial, but the optimal strategy to manage patients with viraemia is unclear. Furthermore, evidence demonstrating the effectiveness of dolutegravir when co-administered with tuberculosis treatment is scarce, particularly in programmatic settings in LMICs. Lastly, it is not known whether nucleoside reverse-transcriptase inhibitor resistance will affect the long-term efficacy of dolutegravir-based regimens in first-line, and potentially second-line ART. Clinical trials, cohorts and surveillance of HIV drug resistance will be required to answer these questions and to maximise the benefits of this new regimen.

Authors: Dorward, J; Lessells, R; Drain, P; Naidoo, K; De Oliveira, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Lancet HIV
• Volume: 5
• Issue: 7
• Pages: e400-e404
• Publication date: 2018-06-05
• Acceptance date: 2018-04-18
• DOI: 10.1016/s2352-3018(18)30093-6
• EISSN: 2352-3018
• ISSN: 2405-4704
• Pmid: 29884404
• Language: English
• Keywords: antiretroviral therapy; adherence; dolutegravir; viral load; HIV; resistance