Treatment Outcomes with Dolutegravir (DTG)

Over the past four decades, antiretroviral therapy (ART) has transformed HIV from a fatal disease into a manageable chronic condition. A major milestone in this evolution is the widespread adoption of dolutegravir (DTG)-based ART, now taken by over 25 million people globally. DTG has largely replaced older regimens, including NNRTI-based first-line and ritonavir-boosted lopinavir (LPV/r)-based second-line therapies, as well as first-line options for children under three.

As DTG was rolled out programmatically across Lesotho, the VICONEL cohort provided a crucial platform to monitor its real-world performance. The nested DO-REAL study offered early evidence of DTG’s short-term effectiveness and tolerability in routine care, confirming high rates of viral suppression and modest reductions in reported side effects. These findings were especially important given the limited real-world data available at the time of WHO’s 2018 recommendation of DTG as the preferred ART. DO-REAL also enabled secondary analyses on SARS-CoV-2 seroprevalence and immune response during the COVID-19 pandemic.

Longer-term follow-up in the broader VICONEL cohort confirmed sustained viral suppression in both adults and children transitioning from NNRTI- to DTG-based regimens. It also showed that even with DTG, low-level viraemia predicted later treatment failure—supporting the 2021 WHO decision to lower the viral load threshold for treatment failure from 1000 to 50 copies/mL. In parallel, the LoDoCA cohort, also embedded within VICONEL, examined treatment satisfaction and symptom profiles—especially gastrointestinal and neuropsychiatric effects—among children and adolescents transitioning from LPV/r to DTG.

Over the past four decades, antiretroviral therapy (ART) has transformed HIV from a fatal disease into a manageable chronic condition. Among the most impactful developments is the widespread adoption of DTG-based ART, now used by over 25 million people globally. As such, it has largely replaced non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART previously used in first-line regimens for most people initiating ART, and ritonavir-boosted lopinavir (LPV/r)-based ART previously used in second-line regimens, or as first-line ART for children initiating ART below three years of age. During this programmatic rollout of DTG, the VICONEL cohort offered an opportunity to assess how DTG outcomes from clinical trials translate to real-world outcomes, monitor the programmatic rollout of DTG, and gain further information on participant-reported outcomes including side effects and tolerability.

The DO-REAL cohort nested within VICONEL showed high short-term viral suppression and possible improvements in certain neuropsychiatric symptoms upon transition from former NNRTI- to DTG-based ART. Subsequent longer-term analyses in VICONEL showed high two-year viral suppression in children and adolescents[JB3]  and adults changing from an NNRTI to DTG. Even with DTG, low-level viraemia was associated with subsequent treatment failure as had previously been shown for other regimens, supporting the lowering of the viral load threshold from 1000 copies/mL to 50 copies/mL in World Health Organisation guidelines since 2021. Finally, the LoDoCA cohort assessed changes in treatment satisfaction and tolerability – including gastrointestinal symptoms commonly associated with LPV/r, and sleep and other neuropsychiatric symptoms previously reported with DTG – among children and adolescents transitioning from LPV/r- to DTG-based ART.

Text from other section, make sure it is represented above: The DO-REAL prospective cohort study assessed virological outcomes as well as self-reported symptoms and side effects after the programmatic roll-out of dolutegravir-based antiretroviral therapy. The World Health Organization first recommended dolutegravir as the preferred treatment option for most people with HIV in 2018. At the time, there was good evidence from randomised trials on its high efficacy and tolerability, though little data was available from routine care settings. DO-REAL provided some of the first insights into short-term treatment outcomes upon programmatic transition to dolutegravir, which has now largely replaced prior first- and second-line treatment regimens across Africa and is currently taken by well over 20 million people worldwide. Results were reassuring, showing high viral suppression and slight reductions in side effects. As the study period coincided with the COVID-19 pandemic, secondary serological analyses allowed assessments of SARS-CoV-2 seropositivity over time and of correlates of the strength of antibody response. DO-REAL was conducted in one hospital and was operationally nested within VICONEL. After its completion, larger analyses on longer-term treatment outcomes with dolutegravir were conducted throughout the broader VICONEL cohort.