Dataset Information

Comparative Clinical Outcomes With Scale-up of Dolutegravir as First-Line Antiretroviral Therapy in Ukraine.

ABSTRACT:

Background

Achievement of the UNAIDS 95-95-95 targets requires ARV regimens that are easy to use, well-tolerated, and cost-effective. Dolutegravir (DTG)-based regimens are efficacious and less costly than other common first-line regimens. This study assessed real-world effectiveness of DTG regimens in treatment-naive people living with HIV in Ukraine.

Methods

We extracted data from the national Medical Information System on all adult patients who initiated antiretroviral therapy (ART) with DTG, lopinavir/ritonavir, or efavirenz (EFV) between October 2017 and June 2018, at 23 large clinics in 12 regions of Ukraine. Viral suppression at 12 ± 3 months and retention at 12 months after treatment initiation were the outcomes of interest.

Results

Of total 1057 patients, 721 had a viral load test within the window of interest, and 652 (90%) had viral load of ≤ 200 copies/mL. The proportion with suppression was lower in the EFV group [aOR = 0.4 (95% confidence interval: 0.2 to 0.8)] and not different in the LPV group [aOR = 1.6 (0.5 to 4.9)] compared with the DTG group. A 24-month or longer gap between diagnosis and treatment was associated with lower odds of suppression [aOR = 0.4 (0.2 to 0.8)]. Treatment retention was 90% (957/1057), with no significant difference by regimen group. History of injecting drug use was associated with decreased retention [aOR = 0.5 (0.3 to 0.8)].

Conclusions

DTG-based regimens were comparable with LPV and more effective than EFV in achieving viral suppression among ART-naive patients in a multisite cohort in Ukraine. Treatment retention was equally high in all 3 groups. This evidence from Ukraine supports the ART Optimization Initiative as a strategy to improve efficiency of the ART program without negatively affecting patient clinical outcomes.

SUBMITTER: Dumchev K

PROVIDER: S-EPMC9472572 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Comparative Clinical Outcomes With Scale-up of Dolutegravir as First-Line Antiretroviral Therapy in Ukraine.

Dumchev Kostyantyn K Kiriazova Tetiana T Riabokon Serhiy S Shost Alyona A Parrish Canada C Shapoval Anna A Germanovych Myroslava M Penner Jeremy J Beste Jason J Puttkammer Nancy N

Journal of acquired immune deficiency syndromes (1999) 20221001 2

<h4>Background</h4>Achievement of the UNAIDS 95-95-95 targets requires ARV regimens that are easy to use, well-tolerated, and cost-effective. Dolutegravir (DTG)-based regimens are efficacious and less costly than other common first-line regimens. This study assessed real-world effectiveness of DTG regimens in treatment-naive people living with HIV in Ukraine.<h4>Methods</h4>We extracted data from the national Medical Information System on all adult patients who initiated antiretroviral therapy ( ...[more]

PMID: 36094487

Similar Datasets

Project description:BackgroundTenofovir diphosphate (TFV-DP) concentration in dried blood spots is a marker of long-term adherence. We investigated the relationship between TFV-DP concentrations and virological outcomes in participants initiating tenofovir-lamivudine-dolutegravir (TLD) as first-line or second-line antiretroviral therapy.SettingThree primary care clinics in Khayelitsha, Cape Town, South Africa.MethodsWe conducted a post hoc analysis of 2 randomized controlled trials of participants initiating TLD. TFV-DP concentrations and viral loads were measured at 12, 24, and 48 weeks. Multivariable logistic regression was performed to assess the association with virological suppression (<50 copies/mL) per natural logarithm increase in TFV-DP concentration. Generalized estimating equations with logit link were used to assess associations with virological rebound. The Akaike Information Criterion and Quasi-likelihood Information Criteria were used to compare models built on continuous TFV-DP data to 4 previously defined concentration categories.ResultsWe included 294 participants in the analysis, 188 (64%) of whom initiated TLD as second-line therapy. Adjusted odds ratios (95% CIs) of virological suppression were 2.12 (1.23, 3.75), 3.11 (1.84, 5.65), and 4.69 (2.81, 8.68) per natural logarithm increase in TFV-DP concentration at weeks 12, 24, and 48, respectively. In participants with virological suppression at week 12, the adjusted odds ratio for remaining virologically suppressed was 3.63 (95% CI: 2.21 to 5.69) per natural logarithm increase in TFV-DP concentration. Models using continuous TFV-DP data had lower Akaike Information Criterion and Quasi-likelihood Information Criteria values than those using categorical data for predicting virological outcomes.ConclusionTFV-DP concentrations in dried blood spots exhibit a dose-response relationship with viral load. Analyzing TFV-DP concentrations as continuous variables rather than conventional categorization may be appropriate.

Project description:IntroductionConcerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals.MethodsWe performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan-Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation.ResultsAbout 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group.ConclusionsIn this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

Project description:Background: Dolutegravir has superior efficacy and tolerability than lopinavir-ritonavir in second-line antiretroviral therapy after failure of a first-line non-nucleoside reverse transcriptase inhibitors-based regimen, when dolutegravir is accompanied by at least one fully active nucleoside reverse transcriptase inhibitor (NRTI). Resistance testing to select NRTIs is not feasible in low- and middle-income countries due to cost and limited laboratory capacity. Evidence suggests that recycling tenofovir plus lamivudine or emtricitabine backbone with dolutegravir could provide an effective second-line option. This study aims to determine the virologic efficacy of tenofovir-lamivudine-dolutegravir (TLD) with and without a lead-in supplementary dose of dolutegravir (to counteract the inducing effect of efavirenz) in patients failing a first-line regimen of tenofovir-emtricitabine-efavirenz (TEE). Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled, Phase II trial, comparing TLD fixed dose combination daily with a lead-in supplementary 50 mg dolutegravir dose versus matching placebo taken 12 hours later for the first 14 days, in patients failing a first-line TEE regimen. The trial will be set in two primary care clinics in Khayelitsha; a large, peri-urban informal settlement in Cape Town, South Africa. We will enrol 130 participants, with follow-up to 48 weeks. The primary endpoint is proportion achieving viral load <50 copies/mL at week 24 using a modified intention-to-treat analysis and the U.S. Food and Drug Administration snapshot algorithm. Secondary endpoints include virologic suppression at weeks 12 and 48, time to suppression, emergence of dolutegravir and new NRTI resistance mutations, safety, and tolerability. Discussion: Impaired viral fitness due to NRTI resistance mutations and dolutegravir's high barrier to resistance provide rationale for switching patients from a failing TEE regimen to TLD; however, clinical evidence regarding virologic efficacy is lacking. This study provides estimates of such a strategy's early virologic efficacy with and without a supplementary dolutegravir dosing. Registration: ClinicalTrials.gov NCT03991013 (19/06/2019).

Dataset Information

Comparative Clinical Outcomes With Scale-up of Dolutegravir as First-Line Antiretroviral Therapy in Ukraine.

Background

Methods

Results

Conclusions

Publications

Comparative Clinical Outcomes With Scale-up of Dolutegravir as First-Line Antiretroviral Therapy in Ukraine.

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