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Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

ABSTRACT: There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ARV therapy.Data from the Quebec HIV Cohort including 10219 PLHIV were collected through routine clinical care at 4 clinical sites in Montreal, Canada. This study includes patients whose ARV therapy was switched to dolutegravir with 2 NRTIs since 2013 with undetectable viral load for ?6 months before switch. The association between exposure and post-switch virologic outcome was measured by marginal hazard ratio estimated using the Inverse probability weighting Cox model.Among the 1199 eligible PLHIV, 478 (39.9%) previously experienced at least one virologic failure or were exposed to mono/dual therapy before dolutegravir switch. Post-switch virologic failure after 30 months occurred in 4.1% (95% CI 2.1-7.9) of exposed compared to 4.1% (95% CI 2.3-7.4) in unexposed participants. The adjusted hazard ratio for the association between exposure and post-switch virologic failure was 0.84 (95% CI 0.35-2.01).Our findings suggest that switch to dolutegravir with 2 NRTIs from a suppressive therapy is a safe option for PLHIV with documented virologic failure and/or previous exposure to mono/dual NRTI therapy.

SUBMITTER: Sangare MN

PROVIDER: S-EPMC7676601 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

Sangaré Mohamed N'dongo MN Baril Jean-Guy JG de Pokomandy Alexandra A Laprise Claudie C Deshaies Catherine C Klein Marina M Thomas Réjean R Tremblay Cécile C Roger Michel M Pexos Costa C Greenwald Zoe Z Machouf Nima N Durand Madeleine M Hardy Isabelle I Dakouo Mamadou M Laporte Louise L Trottier Helen H

Medicine 20201101 47

There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ...[more]

PMID: 33217873

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Project description:BackgroundFollowing reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG.MethodsBetween January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively.ResultsThe incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): - 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: - 7.26 mg/dl, IQR: - 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36.ConclusionWe demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Project description:INTRODUCTION:Dolutegravir (DTG) is recommended as part of first-line antiretroviral therapy (ART) for people living with HIV(PLHIV). We sought to determine the rate of adverse events (AEs) and discontinuations among Thais treated during acute HIV infection (AHI) and switched to DTG-based regimens. METHODS:Thai participants in the SEARCH010/RV254 cohort who initiated ART during AHI and switched to DTG for at least 48 weeks were prospectively observed and included in the analysis. Rates and characteristics of DTG-related AEs and discontinuations were described. RESULTS:A total of 313 Thai participants were included in the analysis. The median age was 29 years, 96% were male, 64% had a Bachelor's degree or higher and 16% had a body mass index (BMI) <18.5 kg/m2 . Participants were on ART for a median of 124 weeks before switching to DTG. The median (IQR) body weight increased from 63 (56 to 70) kg before to 65 (58 to 73) kg (p < 0.0001) after 48 weeks of DTG. Forty-nine (16%) developed DTG-related AEs, corresponding to an incidence of 16.6 per 100 person-years. Neuropsychiatric symptoms were most frequently encountered (n = 25, 8%), followed by laboratory abnormalities (n = 16, 5%). Six (2%) discontinued DTG, corresponding to an incidence of 2.4 per 100 person-years. All discontinuations were due to increased liver enzymes in the presence of hepatitis C virus coinfection. In the multivariate analysis, incident hepatitis C virus infection was the only risk factor for discontinuing DTG (hazard ratio 59.4, 95% CI 8.5 to 297.9, p < 0.0001). Neither low BMI nor concurrent abacavir therapy was associated with discontinuation. CONCLUSIONS:DTG was well tolerated with few discontinuations in this cohort of young men. Incident hepatitis C virus infection was a driver of liver-related AEs leading to discontinuations. In populations at risk, regular testing for hepatitis C virus during ART is recommended to anticipate possible AEs, guide management and improve safety.

Dataset Information

Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

Publications

Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

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