Dolutegravir as maintenance monotherapy: first experiences in HIV-1 patients: Table 1.

Rokx, Casper; Schurink, Carolina A. M.; Boucher, Charles A.; Rijnders, Bart J. A.

doi:10.1093/jac/dkw011

Cited by 25 publications

(23 citation statements)

References 21 publications

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“…Dual therapy consisted of DTG + 3TC (seven studies) or RPV (four studies) or atazanavir (ATV, two studies) or darunavir (DRV, one study). Overall, 14 studies allowed the inclusion of patients with previous virological failure, including five monotherapy studies 18– 20, 22– 24 . In one study, patients with previous InSTI failure were also included 12 .…”

Section: Resultsmentioning

confidence: 99%

“…In one study, patients with previous InSTI failure were also included 12 . Nineteen studies assessed virological outcomes at six months of maintenance therapy, whereas ten of them additionally showed outcomes at one year 8, 11, 12, 24, 27, 29– 33, 35 . Two studies assessed virological outcomes only at 48 weeks 25, 27 .…”

Section: Resultsmentioning

confidence: 99%

“…Two studies assessed virological outcomes only at 48 weeks 25, 27 . Median (or mean) age of participants included in the studies varied from 43 years 11 to 63 years 24 and 27.6% of them were female. 16 studies reported on the median nadir CD4 cell count, which ranged from 90 cells/µl 12 to 399 cells/µl 29 .…”

Section: Resultsmentioning

confidence: 99%

“…All interventional studies adequately addressed incomplete outcome data: proportions of drop-outs were low and outcome data were missing for less than 20% of participants in all studies. Five of seven trials reported on virological outcomes at both time-points of interest for this study (24 and 48 weeks) 8, 11, 24, 29, 35 . There was no evidence of selective reporting in any of the studies.…”

Section: Resultsmentioning

confidence: 99%

“…The high proportion of treatment failures among patients on monotherapy at 48 weeks was driven by the two studies from the Netherlands, which observed between 8 and 20% of VF 8, 24 . Among patients on dual therapy, an estimated 0.4% (95% CI 0.2-0.9) experienced a VF at 24 weeks and 0.7% (95% CI 0.4-1.3) at 48 weeks.…”

Section: Resultsmentioning

confidence: 99%

See 4 more Smart Citations

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

Wandeler

Buzzi²,

Anderegg

et al. 2018

F1000Res

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Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results: Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant’s median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

Wandeler

Buzzi²,

Anderegg

et al. 2018

F1000Res

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Population Pharmacokinetic Analysis of Dolutegravir in Treatment‐Experienced Adults Living with HIV‐1

Chandasana,

Bush,

Ait‐Khaled

et al. 2024

The Journal of Clinical Pharma

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The World Health Organization has recommended the use of dolutegravir (DTG) for both first and second‐line antiretroviral treatment in both adults and children down to 4 weeks of age. We developed a population pharmacokinetic(PopPK) model following oral administration of DTG 50 mg QD and 50 mg BID in HIV‐infected treatment‐experienced adults (607) based on pooled data from four phase 2/3 trials. DTG population pharmacokinetics are described by a one‐compartment model with first‐order absorption, absorption lag‐time, and first‐order elimination. The PopPK parameter estimates were apparent oral clearance (CL/F) = 1.00 L/h, apparent volume of distribution (V/F) = 18.9 L, absorption rate constant (Ka) = 1.99 per hour, and absorption lag time = 0.333 h, respectively. The final model included inter‐individual and inter‐occasion variability on apparent clearance (CL/F). Weight, smoking status, use of metabolic inducers as part of background antiretroviral therapy (ART) classified by their level of induction, use of atazanavir or atazanavir‐ritonavir as part of background ART, and albumin level were predictors of CL/F; weight and albumin level were predictors of V/F; and sex and concomitant use of metal cation‐containing vitamin/mineral supplements were predictors of relative bioavailability (F). The current model‐based analysis suggests that the DTG dose adjustment is not required based on the demographics, laboratory values, smoking status, concomitant use of mild metabolic inducers or inhibitors in the background therapy, or use of metal cation‐containing vitamin/mineral supplements because these covariate effects are not predicted to have a clinically relevant impact on safety and efficacy.

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South African healthcare workers’ knowledge of dolutegravir's drug–drug interactions in the first year of its rollout: a cross‐sectional online survey

2022

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Introduction:In December 2019, dolutegravir-based treatment was recommended as first-line antiretroviral therapy (ART) in South Africa. Dolutegravir has clinically significant interactions with several commonly used drugs, such as rifampicin, metformin and cation-containing medicines. National guidelines detail these interactions and how to manage them. While previous international studies have shown low healthcare worker knowledge of drug-drug interactions, there is a paucity of information on antiretroviral interaction knowledge in the South African setting, where much ART is nurse-led. The study aimed to determine this knowledge and to describe which variables were associated with gaps in knowledge. Methods: An anonymous online survey of healthcare workers in the field of HIV was conducted in August/September 2020. The survey was designed, tested and piloted, and included sections on demographics, guideline access and training, interaction knowledge, counselling and the effect of COVID-19. Dissemination was via e-mail and social media (convenience sampling). Descriptive and inferential analysis was done using proportions and the 95% confidence interval to determine relationships between independent and dependent variables. Research ethics approval was obtained from the University of Cape Town's Human Research Ethics Committee (HREC Ref: 357/2020). Results and discussion: In total, 1950 survey responses were included in the analysis -47.1% nurses, 35.8% doctors and 8.9% pharmacists. When asked whether they were aware that dolutegravir has interactions, 70% said yes, 13.9% said no and 16.1% did not answer. Knowledge of specific interactions and the dosing changes needed was low with a wide range between different drugs: 79.7% knew to double the dolutegravir dose with rifampicin, but with calcium, 5.1% picked both correct dosing options and 33.7% picked one of the two correct options. Access to guidelines and training were positively associated with drug interaction knowledge. Conclusions: There are gaps in the awareness and knowledge of dolutegravir interactions and how to adjust dosing among South African healthcare workers.

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Dolutegravir as maintenance monotherapy: first experiences in HIV-1 patients: Table 1.

Abstract: This case series indicates that dolutegravir monotherapy might be a valuable maintenance option in selected HIV-infected patients who are well suppressed on cART, if confirmed by future randomized clinical trials.

Cited by 25 publications

References 21 publications

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

Virologic failure and HIV drug resistance on simplified, dolutegravir-based maintenance therapy: Systematic review and meta-analysis

Population Pharmacokinetic Analysis of Dolutegravir in Treatment‐Experienced Adults Living with HIV‐1

South African healthcare workers’ knowledge of dolutegravir's drug–drug interactions in the first year of its rollout: a cross‐sectional online survey

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