Dataset Information

Weight gain among treatment-naive persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

ABSTRACT: INTRODUCTION:Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS:Adult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years. RESULTS:Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI). CONCLUSIONS:PWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

SUBMITTER: Bourgi K

PROVIDER: S-EPMC7159248 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

Bourgi Kassem K Jenkins Cathy A CA Rebeiro Peter F PF Palella Frank F Moore Richard D RD Altoff Keri N KN Gill John J Rabkin Charles S CS Gange Stephen J SJ Horberg Michael A MA Margolick Joseph J Li Jun J Wong Cherise C Willig Amanda A Lima Viviane D VD Crane Heidi H Thorne Jennifer J Silverberg Michael M Kirk Gregory G Mathews William C WC Sterling Timothy R TR Lake Jordan J Koethe John R JR

Journal of the International AIDS Society 20200401 4

<h4>Introduction</h4>Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).<h4>Methods</h4>Adult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (P ...[more]

PMID: 32294337

Similar Datasets

Project description:ObjectivesTwo nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs.MethodsBetween June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events.ResultsDuring the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity.ConclusionsThe baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

Project description:In the SAILING study, dolutegravir demonstrated superior virologic efficacy compared with raltegravir in treatment-experienced, integrase strand transfer inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to ≥2 antiretroviral drug classes. Significantly fewer dolutegravir-treated patients demonstrated virologic failure with treatment-emergent resistance than raltegravir-treated patients through 48 weeks. Investigator-selected background therapy (ISBT) included at least one fully active agent, selected on the basis of resistance analysis. Genotypic and phenotypic resistance testing were performed on baseline and time-of-failure samples from patients with protocol-defined virologic failure (PDVF). A post hoc analysis of SAILING (N = 715; 354 dolutegravir, 361 raltegravir) assessed efficacy in subpopulations defined by ISBT activity, resistance profiles, and treatment history. When ISBT contained only nucleoside reverse transcriptase inhibitors (NRTIs), PDVF occurred in 0% (0/32) of dolutegravir-treated patients and 21.9% (7/32) of raltegravir-treated patients (p = .005). In patients harboring M184 V whose ISBT contained lamivudine or emtricitabine plus a second NRTI, 0% (0/13) of dolutegravir- and 33.3% (4/12) of raltegravir-treated patients (p = .026) experienced PDVF. Among patients receiving protease inhibitor (PI)-containing ISBT, 6.0% (18/300) of dolutegravir-treated patients versus 11.8% (36/305) of raltegravir-treated patients (p = .012) experienced PDVF. Darunavir/ritonavir was part of ISBT in 130 dolutegravir-treated patients and 145 raltegravir-treated patients; 6 (4.6%) and 12 (8.3%), respectively, experienced PDVF (difference -3.7%; 95% confidence interval: -10.1% to 2.5%; p = .256). There was no or less virologic failure in treatment-experienced, INSTI-naive subjects receiving dolutegravir versus raltegravir, even when the ISBT was suboptimal or NRTI resistance was present at baseline. These findings are not explained by the use of PI/ritonavir-containing ISBT.

Project description:BackgroundDolutegravir (DTG) is a once-daily unboosted second-generation integrase-inhibitor that along with two nucleoside reverse transcriptase inhibitors is one of several regimens recommended by the United States, United Kingdom and European Union for first-line antiretroviral treatment of people with HIV infection. Our objective was to review the evidence for the efficacy and safety of DTG-based first-line regimens compared to efavirenz (EFV)-based regimens.MethodsWe conducted a systematic review. We comprehensively searched a range of databases as well as conference abstracts and a trials registry. We used Cochrane methods in screening and data collection and assessed each study's risk of bias with the Cochrane tool. We meta-analyzed data using a fixed-effects model. We used GRADE to assess evidence quality.ResultsFrom 492 search results, we identified two randomized controlled trials, reported in five peer-reviewed articles and one conference abstract. One trial tested two DTG-based regimens (DTG + abacavir (ABC) + lamivudine (3TC) or DTG + tenofovir + emtricitabine) against an EFV-based regimen (EFV+ ABC+3TC). The other trial tested DTG+ABC+3TC against EFV+ABC+3TC. In meta-analysis, DTG-containing regimens were superior to EFV-containing regimens at 48 weeks and at 96 weeks (RR = 1.10, 95% CI 1.04-1.16; and RR = 1.12, 95% CI 1.04-1.21, respectively). In one trial, the DTG-containing regimen was superior at 144 weeks (RR = 1.13, 95% CI 1.02-1.24). DTG-containing regimens were superior in reducing treatment discontinuation compared to those containing EFV at 96 weeks and at 144 weeks (RR = 0.27, 95% CI 0.15-0.50; and RR = 0.28, 95% CI 0.16-0.48, respectively). Risk of serious adverse events was similar in each regimen at 96 weeks (RR = 1.15, 95% CI 0.80-1.63) and 144 weeks (RR = 0.93, 95% CI 0.68-1.29). Risk of bias was moderate overall, as was GRADE evidence quality.ConclusionsDTG-based regimens should be considered in future World Health Organization guidelines for initial HIV treatment.

Dataset Information

Weight gain among treatment-naive persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

Publications

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets